Narrative Review
The roles of perivascular adipose tissue in obesity-related hypertension

Cam Ly Nguyen (1), Ernesto L. Schiffrin (1)
Published online: May 13th, 2026
Volume 23, Issue 1

¹Department of Medicine, McGill University, Montreal, QC, Canada
Corresponding Author, Cam Ly Nguyen: cam-ly.nguyen@mail.mcgill.ca
DOI: 10.26443/mjm.v23i1.1157

Introduction

Overview of obesity

Obesity is a chronic and multisystem condition which is associated with increased morbidity and mortality worldwide. Excessive fat deposits generate unfavourable hemodynamic modifications, dysregulate fatty acid and glucose metabolism, trigger insulin resistance and inflammation, and eventually damage several organs. (1) According to the World Health Organization (WHO), the global prevalence of adult obesity has more than doubled since 1990, and that of adolescent obesity has quadrupled. (2) In 2022, 43% of adults aged 18 and older (2.5 billion adults) were overweight, and 16% (890 million adults) were obese. Over 390 million children and adolescents aged five to 19 were overweight, including 160 million who were obese. Alarmingly, 37 million children aged five and younger were overweight. If there are no breakthroughs in obesity management, the worldwide cost of overweight and obesity can reach three trillion US dollars per year by 2030.

Obesity is diagnosed by calculating the body mass index (BMI) that is weight (kilograms) divided by height squared (metres squared). Table 1 specifies the classification of whether a White, Hispanic, or Black individual is underweight, normal weight, overweight, or obese based on BMI as used by the National Institute of Health (NIH) and WHO. (3) As the cut-offs underestimate the obesity risks in the Asian and South Asian populations, an Asian and South Asian individual may be deemed overweight and obese with a lower BMI (BMI of 23–24.9 kg/m² to be overweight and BMI of more than 25 kg/m² to be obese). In 2019, higher-than-optimal BMI was estimated to result in five million deaths from noncommunicable diseases, comprising cardiovascular diseases (CVDs). (4) However, because individual variations exist, and BMI does not differentiate between lean muscle mass and adipose tissue mass, BMI is insufficient as the sole means of determining whether an individual is obese. (1, 3) Furthermore, an obesity paradox has been noted, whereby obesity evaluated by BMI may be benign rather than have pathological consequences. (1) Girth, which is abdominal circumference as evaluated by the waist/hip ratio, may be a better way to assess pathological obesity. This phenomenon manifests as a contrast between apples (increased abdominal circumference) and pears (increased hip circumference) – the former associated with cardiometabolic pathological conditions including CVDs, diabetes, and metabolic dysfunction-associated fatty liver disease (MAFLD), all leading to higher mortality.

Overview of hypertension

High blood pressure (BP), systemic hypertension (HTN), or HTN is the leading risk factor for global disease burden and mortality. HTN causes chronic inflammation and predisposes to multiple detrimental complications in the cardiovascular system, kidneys, brain, and mental health, including cognitive decline and dementia. (5) According to WHO's report on HTN in 2023, the number of individuals with HTN doubled from 650 million to 1.3 billion between 1990 and 2019. Among individuals aged 30 to 79 with HTN, only 54% have been diagnosed, 42% are being treated, and 21% are considered to have the condition controlled. If countries can mobilize to achieve WHO's goal of 50% population HTN control by the year 2050, 76 million cardiovascular deaths and 450 million disability-adjusted life years may be avoided. In addition, the economic benefits may be 18 times greater than business as usual.

HTN has been defined by the BP levels at or above which reducing BP will decrease the cardiovascular risks associated with elevated BP. (6) This threshold has classically been 140/90 mm Hg based on actuarial data from the insurance industry. Nevertheless, it is worth noting that among individuals aged 40 to 69, cardiovascular risks progressively rise from as low as 115/75 mm Hg with a two-fold escalation in death rates from cardiovascular causes for every 20/10 mm Hg increment. (7) Furthermore, the Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that hypertensive individuals at high risk of CVDs with systolic BP (SBP) of 130–180 mm Hg would benefit from reducing SBP to below 120 mm Hg. (8) Thus, the new threshold has been proposed to be 130/80 mm Hg for hypertensive individuals at high cardiovascular risk: chronic kidney disease patients, diabetic people, elderly people, and people with a Framingham Risk Score of 15% or higher. (6) In fact, the 2017 American Heart Association/American College of Cardiology guideline for HTN management has defined HTN for all individuals as BP at or above 130/80 mm Hg. (9) Although there is not a different BP cut-off for obese individuals, these people are 3.5 times more susceptible to developing HTN. (10) In fact, the Framingham Heart Study revealed 60–70% of HTN is caused by obesity.

Adipose tissue, particularly perivascular adipose tissue, plays a role in obesity-related hypertension

Massive expansion and remodelling of adipose tissue in obesity exert differential impacts on specific adipose tissue depots that have differential contributions to chronic systemic inflammation and HTN. (11) Initially thought to be exclusively an energy-storing organ, adipose tissue has been recognized to be highly dynamic and responsible for several processes, including metabolism and modulation of vascular tone. Adipose tissue can be categorized based on the cellular composition as white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue. During pregnancy, lactation, and post-lactation, subcutaneous WAT can transdifferentiate into pink adipose tissue. Adipose tissue can also be categorized based on the anatomical localization as visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), gluteofemoral adipose tissue (GAT), epicardial adipose tissue (EAT), and perivascular adipose tissue (PVAT). The focus of this paper – PVAT – is a heterogenous, metabolically active, endocrine organ surrounding most blood vessels, except cerebral and pulmonary ones. (12) Obesity is associated with an increase in PVAT mass and PVAT dysfunction, contributing to obesity-related HTN and target organ damage.

Discussion

Obesity induces PVAT dysfunction

Obesity-induced PVAT dysfunction results from lipid spillover, hypoxia, and adipocyte apoptosis. Typically, the healthy PVAT consists of white-like and brown-like adipocytes, immune cells, stem cells, microvasculature, and nerves, but the exact phenotype depends on the anatomical location and may vary with the individual's health status. (12) Obesity is characterized by excess fatty acids stored in adipocytes that may be increased in number but mostly in size. (13, 14) Despite exhibiting some WAT histological properties, perivascular adipocytes are less differentiated and have less lipid storage capacity than white adipocytes. (15) Therefore, lipid spillover, ectopic fat deposition, and lipotoxicity occur after the storage capacity of perivascular adipocytes is exceeded. (13) Because the hypertrophic expansion of perivascular adipocytes is not supported by a similar rise in angiogenesis rates, some adipocytes are left outside of the existing vasculature's oxygen diffusion zone, resulting in hypoxia and vasoconstriction. (16) Oxidative stress is enhanced as nitric oxide synthase uncoupling results in the production of superoxide instead of nitric oxide (NO). (14) Due to the increased reaction between superoxide and NO, vascular nitrotyrosine (a marker of peroxynitrite production) increases with nitration of proteins and leads to their dysfunction. Moreover, the aldosterone levels elevate in obesity, upregulating the expression of VCAM-1 (vascular adhesion molecule-1), PECAM-1 (platelet endothelial cell adhesion molecule-1), and ICAM-1 (intercellular adhesion molecule-1) as well as activating the NLRP3 (NLR family pyrin domain containing 3) inflammasome. (14, 17, 18) Consequently, dysfunctional perivascular adipocytes display abnormal Toll-like receptor signalling, vasoactive adipokine secretion, and immune cell recruitment. (13, 19) Adipocyte apoptosis happens when perivascular adipocytes can no longer tolerate the stress signals of nutrient overload and oxidative stress. (13) Despite evidence that brown-like adipocytes in PVAT may counterbalance the white-like ones and counteract obesity-induced cardiometabolic disorders, there is also evidence that BAT activation increases heart rate and becomes detrimental to cardiovascular health. (20, 21) Overall, obesity severely disrupts PVAT's homeostasis via various mechanisms involving NO production, vasoactive adipokine release, immune cell infiltration, and inflammation, thereby contributing to obesity-related HTN.

PVAT produces vasoactive factors implicated in obesity-related hypertension

PVAT has been argued to be the fourth layer of the normal arterial wall (tunica adiposa) since the tissue is capable of modulating vascular tone, vascular endothelial function, and vascular smooth muscle cell (VSMC) growth and proliferation, leading to HTN. (12, 14) PVAT triggers both vasodilatation and vasoconstriction via endocrine and paracrine mechanisms. Multiple studies have shown that PVAT loses its anticontractile effects and potentiates vasoconstriction under certain pathophysiological conditions comprising obesity and HTN. (14, 22)

Anticontractile PVAT-derived factors

PVAT-derived adiponectin, hydrogen sulphide (H₂S), angiotensin (Ang) 1-7, and NO have been the focus of many studies as vasodilators that protect against obesity-related HTN in animal models and humans. Adiponectin in different polymeric forms causes vasodilatation by acting on vascular endothelial cells and VSMCs, in addition to downregulating plasma glucose levels and impacting macrophage polarization. (23) H₂S also triggers vasodilatation via endothelium-dependent and -independent mechanisms besides mediating oxidative stress, macrophage polarization, and inflammation. (24) Ang 1-7, a member of the renin-angiotensin-aldosterone system (RAAS), induces vasodilatation via endothelium-dependent mechanisms and restores glucose tolerance. (25, 26) These anticontractile PVAT-derived factors stimulate NO production, which can directly elicit vasodilatation following diffusion to VSMCs or indirectly by increasing adiponectin. (22, 27) Based on animal models, other anticontractile PVAT-derived factors may include palmitic acid methyl ester and omentin; however, more research is needed. (28, 29) Regardless, all mentioned factors have been detected to decline in obesity and HTN.

Pro-contractile PVAT-derived factors

PVAT-derived superoxide anion, aldosterone, Ang II, and prostaglandins counteract anticontractile PVAT-derived factors and cause vasoconstriction, resulting in obesity-related HTN. Superoxide anion is a free radical oxygen species, which enhances vasoconstriction in obese animal models by raising oxidative stress as well as lowering H₂S and NO bioavailability. (14) Superoxide anion production can be stimulated by aldosterone and Ang II, final mediators of the RAAS and in the case of Ang II, an antagonist of Ang 1-7. (18, 26, 30) Aldosterone and Ang II elicit oxidative stress generation, vasoconstriction, and immune cell recruitment in obese animal models and humans. These pro-contractile PVAT-derived factors have been documented to increase in obesity and HTN. On the other hand, prostaglandins – arachidonic acid-derived metabolites – assume different roles depending on the individual's health status. For instance, prostaglandins augment serotonin- and phenylephrine-induced vasoconstriction of the aorta from obese mice but not lean ones. (31) The roles of chemerin and resistin in vasoconstriction and obesity-related HTN have also been suggested in animal models. Chemerin positively correlates with insulin resistance, more sympathetic nerve-induced vasoconstriction, and immune cell infiltration. (32, 33) Primarily secreted by macrophages, resistin attenuates insulin-related and endothelium-dependent, bradykinin-induced vasodilatation as well as promotes pro-contractile endothelin-1 (ET-1) expression. (34, 35)

PVAT-derived factors exhibiting both anticontractile and pro-contractile properties

PVAT-derived leptin, hydrogen peroxide (H₂O₂), and catecholamines demonstrate anticontractile and pro-contractile properties via different mechanisms, depending on the individual's health status and the factor's concentration. In addition to controlling appetite, energy expenditure, and body weight, leptin causes vasodilatation by targeting vascular endothelial cells and VSMCs in animal models. (36) However, obesity-induced chronically high leptin levels trigger more ET-1 release, contributing to vasoconstriction and higher peripheral resistance. (36, 37) Similarly, H₂O₂ elicits vasodilatation by influencing vascular endothelial cells and VSMCs, but obesity-induced higher H₂O₂ levels lead to vasoconstriction in animal models and humans. (19) Human perivascular adipocytes can synthesize catecholamines de novo or take up and store catecholamines from the sympathetic nervous system, forming a reservoir of noradrenaline, dopamine, and serotonin that causes vasoconstriction. (38) In contrast, immune cells in PVAT of animal models can secrete catecholamines that enhance adiponectin and NO production, triggering vasodilatation. (39, 40) Recently, visfatin has been investigated for its potential roles in vasoconstriction, endothelial dysfunction, and stimulated VSMC proliferation in small resistance arteries of rats and humans but vasodilatation in large conduit arteries of rats. (41, 42) Higher visfatin levels are observed in hypertensive obese individuals. (43)

Immune cells in PVAT contribute to obesity-related hypertension

In response to obesity-induced inflammation, innate and adaptive immune cells in PVAT undergo several changes. As first confirmed in 2010 by Viel and co-authors, inflammation and the immune system play an essential role in HTN. (17) Immune cells interact with one another, crosstalk with perivascular adipocytes, and modify the vascular reactivity in obesity-related HTN.

Innate immune cells

Neutrophils, mast cells, and dendritic cells (DCs) contribute to obesity-related HTN. Neutrophils are early responders to obesity: transiently rise in obese individuals and secrete elastase that enhances glucose intolerance and insulin resistance. (44, 45) Furthermore, obesity-induced higher levels of circulating neutrophils and accumulated neutrophils in microvasculature positively correlate with BP in animal models and humans. (44, 46, 47) Neutrophils regulate vascular dysfunction by generating superoxide anion, augmenting oxidative stress, and reducing NO bioavailability. Additionally, neutrophil extracellular traps (NETs) are created by neutrophil-derived extracellular DNA strings in mice upon Ang II stimulation. (44, 45) NETs promote endothelial damage and exert prothrombotic properties. As one of the first cell populations to migrate to inflammation sites, neutrophils facilitate the recruitment of DCs, macrophages, and lymphocytes. DCs significantly increase from negligible levels in the lean phenotype to levels comparable to macrophages in mice following a high-fat diet. (48, 49) The larger DC population in PVAT has been linked to oxidative stress, impaired anticontractile properties, and overproduction of proinflammatory cytokines. (50, 51) As antigen-presenting cells, DCs also play a critical role in activating T cells. Upon Ang II stimulation, DCs produce IL-23 that regulates the differentiation and maintenance of IL-17-producing T cells. Moreover, a subclass of DCs – plasmacytoid DC – causes vasoconstriction and HTN in response to PVAT-derived chemerin. (32) Nevertheless, because DCs and macrophages all express CD11b and F4/80, it has been complicated to isolate the roles of PVAT-derived DCs and macrophages in obesity and HTN. (48) The number of mast cells also increases in obese animal models and humans, and control of the mast cell population using pharmacological stabilizers can mitigate obesity in mice. (52) However, the specific roles of mast cells in obesity remain controversial. Some researchers believe that mast cells directly take part in insulin resistance and the onset of obesity, whereas others claim that mast cells play no essential roles in obesity. (52, 53) Regardless, mast cells are implicated in PVAT's mediation of the vascular tone by triggering local acute inflammatory responses in animal models. (45)

In 2005, De Ciuceis and co-authors were the first to identify the roles of a specific individual immune cell population – macrophages – in the development of experimental HTN. (54) Macrophages exhibit higher numbers and activation levels in obese and hypertensive patients via autocrine signals and interactions with other immune cell populations. (12) As previously mentioned, macrophages are the primary source of resistin that positively correlates with BP in humans. (35) Macrophage polarization assumes a crucial role in the proinflammatory shift in response to obesity. (55) Specifically, aldosterone, chemerin- and neutrophil-stimulated increase of M1 macrophages is associated with insulin resistance, atherosclerosis, and HTN as M1 macrophages induce oxidative stress, decrease H₂S bioavailability, and release proinflammatory cytokines. (18, 24, 32, 44, 56) Meanwhile, adiponectin-, H₂S-, and eosinophil-stimulated increase of M2 macrophages counteracts M1 macrophages and maintains PVAT's homeostasis via adipocyte turnover, lipid buffering, and modulation of sympathetic drive. (55, 57) Nevertheless, because macrophages are late responders to obesity, the significance of their interactions with other immune cell populations remains a matter of debate.

In contrast to other innate immune cell types, the number of eosinophils in mice declines in response to a high-fat diet. (58) Eosinophil-deficient mice have been proven to display impaired glucose tolerance, lose PVAT's anticontractile properties, and have high peripheral resistance, which may be rescued by eosinophil reconstitution. (40, 45) Eosinophils maintain PVAT's homeostasis and elicit vasodilatation by producing interleukin (IL)-4 and IL-13 and sustaining M2 macrophage polarization. (39, 40, 57)

Adaptive immune cells

Shortly following a high-fat diet, the total B-cell number as well as the cell numbers of the B-1 and B-2 subpopulations in mice all rise and correlate with Ang II-induced BP elevation. (59, 60) B cell-deficient obese mice are protected against obesity-related diseases in spite of weight gain. (61) Specifically, B-2 cells aggravate insulin resistance and atherosclerosis in mice by secreting atherogenic IgG antibodies and promoting proinflammatory T cells, whereas B-1 cells assume the opposing, protective role and attenuate glucose intolerance, vascular dysfunction, and inflammation in mice and humans by releasing atheroprotective IgM antibodies. (60, 61) How the two B-cell subpopulations act on vascular function is particularly interesting, considering that the B-1/B-2 ratio is ten-fold higher in murine PVAT than in the spleen and bone marrow.

The conventional alpha/beta (αβ) T-cell subpopulations undergo different changes in obesity: the frequencies of proinflammatory CD8+ cytotoxic T (Tc) cells, CD4+ helper T-1 (Th1) cells, and CD4+ helper T-17 (Th17) cells rise, while those of anti-inflammatory CD4+ helper T-2 (Th2) cells and CD4+ or CD8+ regulatory T (Treg) cells decline. (17, 30) Tc cells play an important role in both the initiation and maintenance of obesity, inflammation, and HTN in animal models and humans. (62, 63) CD8-deficient animal models have less glucose intolerance, proinflammatory cytokine production, and hypertensive responses to Ang II. Furthermore, it is well-known that Th1 and Th2 cells counteract and inhibit the cytokine secretion of the other. (45, 64) Th1 cells release proinflammatory IL-2, interferon (IFN)-γ, and tumour necrosis factor (TNF)-α and support M1 macrophage polarization, whereas Th2 cells produce anti-inflammatory IL-4 and enhance M2 macrophage polarization. (63, 64) Since the Th1/Th2 ratio increases in obese animal models and humans, proinflammatory cytokine secretion and M1 macrophage polarization by Th1 are favoured, resulting in more vascular dysfunction and inflammation. (64) Meanwhile, more IL-17 is released by Th17 cells in obese animal models and humans, contributing to and sustaining HTN as the proinflammatory cytokine augments oxidative stress and impairs vascular function. (45, 63) IL-17 can also be produced by the unconventional innate-like gamma/delta (γδ) T-cell population that is increased in obesity and promotes insulin resistance and inflammation. (45, 50, 51, 63, 65) Mice devoid of γδ T cells are protected against Ang II-induced BP elevation, vascular dysfunction, and T-cell activation in PVAT. (66) CD28 is a co-stimulatory T-cell receptor that plays a role in γδ T-cell survival and proliferation. (67) CD28-expressing δ T cells are elevated in PVAT of hypertensive mice and SAT of obese humans. The total Treg-cell number is reduced in obese animal models and humans, along with their beneficial mediation of insulin resistance, vascular dysfunction, and immune homeostasis via cell-cell contact mechanisms and anti-inflammatory cytokine release. (17, 50, 63) In 2011 and 2012, the Schiffrin research group published two papers proving the protective roles of CD4+ Treg cells against both aldosterone- and Ang II-induced vascular injury and HTN in mice. (56, 68) Although not examined in PVAT, CD8+ Treg cells have recently been detected with higher percentages within the CD8+ T-cell population in the circulation, VAT, and SAT of obese humans, possibly as a compensatory mechanism for the smaller CD4+ Treg-cell population. (69)

Therapeutic approaches to obesity-related hypertension

The non-pharmacological interventions to relieve obesity-related HTN are lifestyle modifications and bariatric surgery. The first recommended management strategy, lifestyle modifications, has been emphasized by different guidelines as a non-invasive, inexpensive, and sustainable method to alleviate obesity-related HTN. (9) In fact, lifestyle modifications are essential to support and maintain the effects of bariatric surgery and pharmacological interventions. Regular physical activity helps decrease perivascular adipocyte size and proinflammatory markers (e.g., leptin, TNF-α) and immune cells (e.g., M1 macrophages) as well as enhancing anti-inflammatory markers (e.g., adiponectin, NO) and immune cells (e.g., M2 macrophages). (19) Similarly, dietary interventions (e.g., DASH diet, Mediterranean diet, intermittent fasting diet) can improve the metabolic profiles and lower inflammation. (70) Therefore, PVAT inflammation is reversed, PVAT function restored, and blood glucose levels and BP normalized. (19, 70) However, lifestyle modifications can be insufficient as a stand-alone therapy because individuals may be unable to adhere to the exercise and diet regimen, requiring pharmacological and surgical interventions in addition. (71) Bariatric surgery is an invasive approach with some associated risks, especially for individuals in obesity classes II and III. (72) The success of the surgery necessitates the appropriate procedures, as well as a holistic and individualized treatment plan to consider the patient's nutritional and psychosocial attributes before, during, and after the surgery to avoid long-term complications (e.g., excessive weight loss, nutritional deficiencies, and gastrointestinal and renal problems). Successful bariatric surgery can reduce proinflammatory markers and immune cells as well as promote anti-inflammatory markers and immune cells, restoring PVAT function, normalizing BP, and improving metabolic control after six months. (73)

The main pharmacological interventions to ameliorate obesity-related HTN are the RAAS inhibitors, immunomodulatory drugs, and the more recently introduced glucagon-like peptide-1 (GLP-1) agonists (e.g., daily liraglutide or weekly semaglutide), double GLP-1 agonists, and glucagon inhibitory peptide (GIP) agents (e.g., weekly tirzepatide). (18, 30, 51, 71, 74) Firstly, it is worth noting that the effectiveness of anti-obesity medications in decreasing BP varies based on the drug's mechanism of action and the individual's characteristics. (71, 74) Weight-loss medications lead to insufficient BP lowering in most cases and should not be used for individuals with HTN in some cases. Consequently, anti-hypertensive medications are ultimately prescribed for obesity-related HTN. Anti-hypertensive medications include diuretics (especially long-acting ones), RAAS inhibitors, calcium channel blockers, all first-line agents, mineralocorticoid receptor antagonists, and adrenergic blockers. Anti-hypertensive medications targeting the RAAS (angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], and renin inhibitors, although the latter mostly abandoned) demonstrate a broad spectrum of benefits on HTN and the cardiovascular system. Additionally, ACE inhibitors and ARBs exert favourable influences on lipid and glucose abnormalities in obesity. Immunomodulatory drugs have recently received much attention thanks to advances in the understanding that immune mechanisms may be driving obesity and HTN. (18, 30, 51) Protection against obesity, HTN, and comorbidities by inhibition of cytokines and immune cells in experimental animal models suggests potential therapeutic approaches. Moreover, advances in technology (e.g., nanoparticles to deliver immunosuppressants) can support drug innovation and novel treatment strategies. (75) However, comprehensive knowledge of the immune mechanisms in obesity and HTN must be acquired before the available evidence from experimental animal models can be translated into various clinical HTN phenotypes.

Conclusion

The complex interplay between obesity and HTN underscores the necessity for a multifaceted approach to prevention and treatment. Obesity predisposes an individual to HTN via several mechanisms, particularly involving the roles of PVAT. As a heterogenous, metabolically active, endocrine organ surrounding most blood vessels, PVAT regulates vascular tone, vascular endothelial function, and VSMC growth and proliferation. In obesity-related HTN, PVAT becomes dysfunctional. The tissue exhibits abnormal vasoactive adipokine secretion and immune cell infiltration as well as augmented inflammation. Because lifestyle modifications can reduce obesity-related HTN but may be insufficient as a stand-alone treatment, pharmacological and surgical interventions may be required. Given the goals of simultaneously alleviating two conditions and that individual variations exist, therapeutic approaches should be made in a personalized way. Recently, immunomodulatory drugs have emerged as a promising therapeutic approach. However, further research on the immune mechanisms in obesity and HTN must be achieved to formulate effective drugs and mitigate the pressing worldwide health and economic impact of obesity-related HTN.

Acknowledgements

The research reported from the work of ELS was supported by Canadian Institutes of Health Research (CIHR) grants 37917, First Pilot Foundation Grant 143348 and Project Grant PJT 186248, a Canada Research Chair (CRC) on Hypertension and Vascular Research by the CRC Government of Canada/CIHR Program, by the Canada Fund for Innovation, and a Distinguished James McGill Professorship. CLN received a Bourse de Formation à là MAÎTRISE from La Société québécoise d'hypertension artérielle (SQHA).

References

1. Després J-P. Body fat distribution and risk of cardiovascular disease. Circulation. 2012;126(10):1301-13. doi: 10.1161/CIRCULATIONAHA.111.067264
2. World Health Organization. Obesity and overweight [Internet]. 2024 [cited 2026-04-15]. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
3. Weir CB, Jan A. BMI classification percentile and cut off points [Internet]. 2019 [cited 2026-04-15]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541070/
4. Murray CJ, Aravkin AY, Zheng P, Abbafati C, Abbas KM, Abbasi-Kangevari M, et al. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1223-49. doi: 10.1016/s0140-6736(20)30752-2
5. World Health Organization. Global report on hypertension: the race against a silent killer [Internet]. 2023 [cited 2026-04-15]. Available from: https://www.who.int/publications/i/item/9789240081062
6. Schiffrin EL, Calhoun DA, Flack JM. Do we need a new definition of hypertension after SPRINT? Am J Hypertens. 2016;29(10):1127-9. doi: 10.1093/ajh/hpw068
7. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903-13. doi: 10.1016/s0140-6736(02)11911-8
8. Group SR. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103-16. doi: 10.1056/nejmoa1511939
9. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. Hypertension. 2018;71(6):e13-e115. doi: 10.1161/HYP.0000000000000065
10. Kotchen TA. Obesity-related hypertension: epidemiology, pathophysiology, and clinical management. Am J Hypertens. 2010;23(11):1170-8. doi: 10.1038/ajh.2010.172
11. Chait A, Den Hartigh LJ. Adipose tissue distribution, inflammation and its metabolic consequences, including diabetes and cardiovascular disease. Front Cardiovasc Med. 2020;7:522637. doi: 10.3389/fcvm.2020.00022
12. Hillock-Watling C, Gotlieb AI. The pathobiology of perivascular adipose tissue (PVAT), the fourth layer of the blood vessel wall. Cardiovasc Pathol. 2022;61:107459. doi: 10.1016/j.carpath.2022.107459
13. Jiang Y, Guo J-Q, Wu Y, Zheng P, Wang S-F, Yang M-C, et al. Excessive or sustained endoplasmic reticulum stress: one of the culprits of adipocyte dysfunction in obesity. Ther Adv in Endocrinol Metab. 2024;15:20420188241282707. doi: 10.1177/20420188241282707
14. Marchesi C, Ebrahimian T, Angulo O, Paradis P, Schiffrin EL. Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction in a rodent model of metabolic syndrome. Hypertension. 2009;54(6):1384-92. doi: 10.1161/HYPERTENSIONAHA.109.138305
15. Chang L, Villacorta L, Li R, Hamblin M, Xu W, Dou C, et al. Loss of perivascular adipose tissue on peroxisome proliferator–activated receptor-γ deletion in smooth muscle cells impairs intravascular thermoregulation and enhances atherosclerosis. Circulation. 2012;126(9):1067-78. doi: 10.1161/circulationaha.112.104489
16. Goossens GH, Bizzarri A, Venteclef N, Essers Y, Cleutjens JP, Konings E, et al. Increased adipose tissue oxygen tension in obese compared with lean men is accompanied by insulin resistance, impaired adipose tissue capillarization, and inflammation. Circulation. 2011;124(1):67-76. doi: 10.1161/circulationaha.111.027813
17. Viel EC, Lemarié CA, Benkirane K, Paradis P, Schiffrin EL. Immune regulation and vascular inflammation in genetic hypertension. Am J Physi Heart Circ Physiol. 2010;298(3):H938-H44. doi: 10.1152/ajpheart.00707.2009
18. Ferreira NS, Tostes RC, Paradis P, Schiffrin EL. Aldosterone, inflammation, immune system, and hypertension. Am J Hypertens. 2021;34(1):15-27. doi: 10.1093/ajh/hpaa137
19. Stanek A, Brożyna-Tkaczyk K, Myśliński W. The role of obesity-induced perivascular adipose tissue (PVAT) dysfunction in vascular homeostasis. Nutrients. 2021;13(11):3843. doi: 10.3390/nu13113843
20. Singh R, Barrios A, Dirakvand G, Pervin S. Human brown adipose tissue and metabolic health: potential for therapeutic avenues. Cells. 2021;10(11):3030. doi: 10.3390/cells10113030
21. Xue S, Lee D, Berry DC. Thermogenic adipose tissue in energy regulation and metabolic health. Front Endocrinol. 2023;14:1150059. doi: 10.3389/fendo.2023.1150059
22. Saxton SN, Clark BJ, Withers SB, Eringa EC, Heagerty AM. Mechanistic links between obesity, diabetes, and blood pressure: role of perivascular adipose tissue. Physiol Rev. 2019;99(4):1701-63. doi: 10.1152/physrev.00034.2018
23. Yanai H, Yoshida H. Beneficial effects of adiponectin on glucose and lipid metabolism and atherosclerotic progression: mechanisms and perspectives. Int J Mol Sci. 2019;20(5):1190. doi: 10.3390/ijms20051190
24. Comas F, Moreno-Navarrete JM. The impact of H2S on obesity-associated metabolic disturbances. Antioxidants. 2021;10(5):633. doi: 10.3390/antiox10050633
25. Liu C, Lv X-H, Li H-X, Cao X, Zhang F, Wang L, et al. Angiotensin-(1-7) suppresses oxidative stress and improves glucose uptake via Mas receptor in adipocytes. Acta Diabetol. 2012;49(4):291-9. doi: 10.1007/s00592-011-0348-z
26. South AM, Nixon PA, Chappell MC, Diz DI, Russell GB, Shaltout HA, et al. Obesity is associated with higher blood pressure and higher levels of angiotensin II but lower angiotensin-(1-7) in adolescents born preterm. J Pediatr. 2019;205:55-60.e1. doi: 10.1016/j.jpeds.2018.09.058
27. Withers SB, Bussey CE, Saxton SN, Melrose HM, Watkins AE, Heagerty AM. Mechanisms of adiponectin-associated perivascular function in vascular disease. Arterioscler Thromb Vasc Biol. 2014;34(8):1637-42. doi: 10.1161/atvbaha.114.303031
28. Liu C-H, Hsu H-J, Tseng T-L, Lin T-J, Weng W-H, Chen M-F, et al. COMT-catalyzed palmitic acid methyl ester biosynthesis in perivascular adipose tissue and its potential role against hypertension. J Pharmacol Exp Ther. 2020;373(2):175-83. doi: 10.1124/jpet.119.263517
29. Dong Q, Xing W, Li K, Zhou X, Wang S, Zhang H. Tetrahydroxystilbene glycoside improves endothelial dysfunction and hypertension in obese rats: the role of omentin-1. Biochem Pharmacol. 2021;186:114489. doi: 10.1016/j.bcp.2021.114489
30. Rizzoni D, De Ciuceis C, Szczepaniak P, Paradis P, Schiffrin EL, Guzik TJ. Immune system and microvascular remodeling in humans. Hypertension. 2022;79(4):691-705. doi: 10.1161/hypertensionaha.121.17955
31. Meyer MR, Fredette NC, Barton M, Prossnitz ER. Regulation of vascular smooth muscle tone by adipose-derived contracting factor. PloS One. 2013;8(11):e79245. doi: 10.1371/journal.pone.0079245
32. van der Vorst EPC, Mandl M, Müller M, Neideck C, Jansen Y, Hristov M, et al. Hematopoietic chemR23 fuels atherosclerosis by sustaining an M1 macrophage-phenotype and guidance of plasmacytoid dendritic cells to murine lesions. Arterioscler Thromb Vasc Biol. 2019;39(4):685-93. doi: 10.1161/atvbaha.119.312386
33. Xie Y, Liu L. Role of chemerin/chemR23 axis as an emerging therapeutic perspective on obesity-related vascular dysfunction. J Transl Med. 2022;20(1):141. doi: 10.1186/s12967-021-03220-7
34. Dick GM, Katz PS, Farias III M, Morris M, James J, Knudson JD, et al. Resistin impairs endothelium-dependent dilation to bradykinin, but not acetylcholine, in the coronary circulation. Am J Physiol Heart Circ Physiol. 2006;291(6):H2997-H3002. doi: 10.1152/ajpheart.01035.2005
35. Luo J, Huang L, Wang A, Liu Y, Cai R, Li W, et al. Resistin-induced endoplasmic reticulum stress contributes to the impairment of insulin signaling in endothelium. Front Pharmacol. 2018;9:1226. doi: 10.3389/fphar.2018.01226
36. Jamroz-Wiśniewska A, Gertler A, Solomon G, Wood ME, Whiteman M, Bełtowski J. Leptin-induced endothelium-dependent vasorelaxation of peripheral arteries in lean and obese rats: role of nitric oxide and hydrogen sulfide. PloS One. 2014;9(1):e86744. doi: 10.1371/journal.pone.0086744
37. Quehenberger P, Exner M, Sunder-Plassmann R, Ruzicka K, Bieglmayer C, Endler G, et al. Leptin induces endothelin-1 in endothelial cells in vitro. Circ Res. 2002;90(6):711-8. doi: 10.1161/01.res.0000014226.74709.90
38. Ayala-Lopez N, Pereira-Hicks C, Burnett R, Fink GD, Watts SW. Human perivascular adipose tissue contains an adrenergic system. FASEB Jl. 2016;30(S1):719.12-.12. doi: 10.1096/fasebj.30.1_supplement.719.12
39. Nguyen KD, Qiu Y, Cui X, Goh YS, Mwangi J, David T, et al. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature. 2011;480(7375):104-8. doi: 10.1038/nature10653
40. Withers SB, Forman R, Meza-Perez S, Sorobetea D, Sitnik K, Hopwood T, et al. Eosinophils are key regulators of perivascular adipose tissue and vascular functionality. Sci Rep. 2017;7(1):44571. doi: 10.1038/srep44571
41. Yamawaki H, Hara N, Okada M, Hara Y. Visfatin causes endothelium-dependent relaxation in isolated blood vessels. Biochem Biophys Res Commun. 2009;383(4):503-8. doi: 10.1016/j.bbrc.2009.04.074
42. Vallejo S, Romacho T, Angulo J, Villalobos LA, Cercas E, Leivas A, et al. Visfatin impairs endothelium-dependent relaxation in rat and human mesenteric microvessels through nicotinamide phosphoribosyltransferase activity. PloS One. 2011;6(11):e27299. doi: 10.1371/journal.pone.0027299
43. Rotkegel S, Chudek J, Spiechowicz-Zaton U, Ficek R, Adamczak M, Wiecek A. The effect of sodium restricted diet on plasma visfatin levels in hypertensive patients with visceral obesity. Kidney Blood Press Res. 2013;37(2-3):124-31. doi: 10.1159/000350066
44. Uribe-Querol E, Rosales C. Neutrophils actively contribute to obesity-associated inflammation and pathological complications. Cells. 2022;11(12):1883. doi: 10.3390/cells11121883
45. Berillo O, Schiffrin EL. Advances in understanding of the role of immune cell phenotypes in hypertension and associated vascular disease. Can J Cardiol. 2024;40(12):2321-39. doi: 10.1016/j.cjca.2024.08.270
46. Siedlinski M, Jozefczuk E, Xu X, Teumer A, Evangelou E, Schnabel RB, et al. White blood cells and blood pressure: a Mendelian randomization study. Circulation. 2020;141(16):1307-17. doi: 10.1161/circulationaha.119.045102
47. Small DM, Allan-Rahill NH, Buglione AE, Abd Elmagid LM, Vaquerano SA, Mistry AA, et al. Arrested neutrophils in capillaries is a novel mechanism of myocardial hypoperfusion in heart failure with preserved ejection fraction. FASEB J. 2022;36. doi: 10.1096/fasebj.2022.36.S1.R4269
48. Cho KW, Zamarron BF, Muir LA, Singer K, Porsche CE, DelProposto JB, et al. Adipose tissue dendritic cells are independent contributors to obesity-induced inflammation and insulin resistance. J Immunol. 2016;197(9):3650-61. doi: 10.4049/jimmunol.1600820
49. Qiu T, Li M, Tanner MA, Yang Y, Sowers JR, Korthuis RJ, et al. Depletion of dendritic cells in perivascular adipose tissue improves arterial relaxation responses in type 2 diabetic mice. Metabolism. 2018;85:76-89. doi: 10.1016/j.metabol.2018.03.002
50. Caillon A, Paradis P, Schiffrin EL. Role of immune cells in hypertension. Br J Pharmacol. 2019;176(12):1818-28. doi: 10.1111/bph.14427
51. Higaki A, Mahmoud AUM, Paradis P, Schiffrin EL. Role of interleukin-23/interleukin-17 axis in T-cell-mediated actions in hypertension. Cardiovasc Res. 2021;117(5):1274-83. doi: 10.1093/cvr/cvaa257
52. Shi MA, Shi GP. Different roles of mast cells in obesity and diabetes: lessons from experimental animals and humans. Front Immunol. 2012;3:7. doi: 10.3389/fimmu.2012.00007
53. Chmelař J, Chatzigeorgiou A, Chung K-J, Prucnal M, Voehringer D, Roers A, et al. No role for mast cells in obesity-related metabolic dysregulation. Front Immunol. 2016;7:524. doi: 10.3389/fimmu.2016.00524
54. De Ciuceis C, Amiri F, Brassard P, Endemann DH, Touyz RM, Schiffrin EL. Reduced vascular remodeling, endothelial dysfunction, and oxidative stress in resistance arteries of angiotensin II–infused macrophage colony-stimulating factor–deficient mice. Arterioscler Thromb Vasc Biol. 2005;25(10):2106-13. doi: 10.1161/01.ATV.0000181743.28028.57
55. Soedono S, Julietta V, Nawaz H, Cho KW. Dynamic roles and expanding diversity of adipose tissue macrophages in obesity. J Obes Metab Syndr. 2024;33(3):193-212. doi: 10.7570/jomes24030
56. Kasal DA, Barhoumi T, Li MW, Yamamoto N, Zdanovich E, Rehman A, et al. T regulatory lymphocytes prevent aldosterone-induced vascular injury. Hypertension. 2012;59(2):324-30. doi: 10.1161/hypertensionaha.111.181123
57. Zhang Y, Yang P, Cui R, Zhang M, Li H, Qian C, et al. Eosinophils reduce chronic inflammation in adipose tissue by secreting Th2 cytokines and promoting M2 macrophages polarization. Int J Endocrinol. 2015;2015(1):565760. doi: 10.1155/2015/565760
58. Bolus WR, Peterson KR, Hubler MJ, Kennedy AJ, Gruen ML, Hasty AH. Elevating adipose eosinophils in obese mice to physiologically normal levels does not rescue metabolic impairments. Mol Metab. 2018;8:86-95. doi: 10.1016/j.molmet.2017.12.004
59. Chan CT, Sobey CG, Lieu M, Ferens D, Kett MM, Diep H, et al. Obligatory role for B cells in the development of angiotensin II–dependent hypertension. Hypertension. 2015;66(5):1023-33. doi: 10.1161/hypertensionaha.115.05779
60. Srikakulapu P, Upadhye A, Rosenfeld SM, Marshall MA, McSkimming C, Hickman AW, et al. Perivascular adipose tissue harbors atheroprotective IgM-producing B cells. Front Physiol. 2017;8. doi: 10.3389/fphys.2017.00719
61. Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med. 2011;17(5):610-7. doi: 10.1038/nm.2353
62. Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15(8):914-20. doi: 10.1038/nm.1964
63. Wang Q, Wang Y, Xu D. The roles of T cells in obese adipose tissue inflammation. Adipocyte. 2021;10(1):435-45. doi: 10.1080/21623945.2021.1965314
64. Schmidt V, Hogan AE, Fallon PG, Schwartz C. Obesity-mediated immune modulation: one step forward, (Th)2 steps back. Front Immunol. 2022;13:932893. doi: 10.3389/fimmu.2022.932893
65. Shokoples BG, Comeau K, Higaki A, Ferreira NS, Caillon A, Berillo O, et al. Angiotensin II-induced a steeper blood pressure elevation in IL-23 receptor-deficient mice: role of interferon-γ-producing T cells. Hypertens Res. 2023;46(1):40-9. doi: 10.1038/s41440-022-01055-3
66. Caillon A, Mian MOR, Fraulob-Aquino JC, Huo K-G, Barhoumi T, Ouerd S, et al. γδ T cells mediate angiotensin II-induced hypertension and vascular injury. Circulation. 2017;135(22):2155-62. doi: 10.1161/circulationaha.116.027058
67. Berillo O, Comeau K, Caillon A, Leclerc S, Shokoples BG, Mahmoud AU, et al. CD28-expressing δ T cells are increased in perivascular adipose tissue of hypertensive mice and in subcutaneous adipose tissue of obese humans. J Hypertens. 2024;42(7):1256-68. doi: 10.1097/hjh.0000000000003725
68. Barhoumi T, Kasal DA, Li MW, Shbat L, Laurant P, Neves MF, et al. T regulatory lymphocytes prevent angiotensin II-induced hypertension and vascular injury. Hypertension. 2011;57(3):469-76. doi: 10.1161/hypertensionaha.110.162941
69. Barbosa P, Pinho A, Lázaro A, Rosendo-Silva D, Paula D, Campos J, et al. CD8+ Treg cells play a role in the obesity-associated insulin resistance. Life Sci. 2024;336:122306. doi: 10.1016/j.lfs.2023.122306
70. Vargas G, Azarbal J, Tota-Maharaj R. A comparative review of established diets for prevention of cardiovascular disease and newer dietary strategies. Curr Probl Cardiol. 2021;46(3):100582. doi: 10.1016/j.cpcardiol.2020.100582
71. Hall ME, Omoto ACM, Do Carmo JM, Da Silva AA, Hall JE. 37 - Obesity and hypertension: pathophysiology and treatment. In: Bakris GL, Sorrentino MJ, Laffin LJ, editors. Hypertension. 4th ed. New Delhi: Elsevier; 2024. p. 413-26.
72. Aderinto N, Olatunji G, Kokori E, Olaniyi P, Isarinade T, Yusuf IA. Recent advances in bariatric surgery: a narrative review of weight loss procedures. Ann Med Surg. 2023;85(12):6091-104. doi: 10.1097/MS9.0000000000001472
73. Aghamohammadzadeh R, Greenstein AS, Yadav R, Jeziorska M, Hama S, Soltani F, et al. Effects of bariatric surgery on human small artery function: evidence for reduction in perivascular adipocyte inflammation, and the restoration of normal anticontractile activity despite persistent obesity. J Am Coll Cardiol. 2013;62(2):128-35. doi: 10.1016/j.jacc.2013.04.027
74. Michałowska J, Miller-Kasprzak E, Bogdański P. Incretin hormones in obesity and related cardiometabolic disorders: the clinical perspective. Nutrients. 2021;13(2):351. doi: 10.3390/nu13020351
75. Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R. Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov. 2021;20(2):101-24. doi: 10.1038/s41573-020-0090-8