Skip to main content

Perivascular Adipose Tissue

  • Chapter
  • First Online:
Textbook of Vascular Medicine

Abstract

Contractility of small arteries determines systemic blood pressure, so the microvasculature is often invoked as a therapeutic target for hypertension and its consequences. This is especially the case for obesity-related hypertension which is characterized by small artery dysfunction. In the context of obesity-related cardiovascular disease, there has been much interest in white adipose tissue. The adipose tissue which surrounds small arteries – also known as perivascular adipose tissue (PVAT) – is not merely a structural support for the arteries but also influences the contractile function of the artery, inducing dilation. This local vascular coupling mechanism is achieved through the release of several key paracrine hormones which alter vascular function. In obesity, however, inflammation in PVAT degrades the vasodilatory effect on the arteries, and this leads to hypertension. We also describe a novel CT imaging approach through which the relationship between arteries and the PVAT can be quantified in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–81.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Wang YC, McPherson K, Marsh T, Gortmaker SL, Brown M. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet. 2011;378(9793):815–25.

    Article  PubMed  Google Scholar 

  3. Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373(9669):1083–96.

    Article  PubMed  Google Scholar 

  4. Lee HY, Després JP, Koh KK. Perivascular adipose tissue in the pathogenesis of cardiovascular disease. Atherosclerosis. 2013;230(2):177–84.

    Article  CAS  PubMed  Google Scholar 

  5. Oriowo MA. Perivascular adipose tissue, vascular reactivity and hypertension. Med Princ Pract. 2014;24 Suppl 1:29–37.

    PubMed  Google Scholar 

  6. Lee DE, Kehlenbrink S, Lee H, Hawkins M, Yudkin JS. Getting the message across: mechanisms of physiological cross talk by adipose tissue. Am J Physiol Endocrinol Metab. 2009;296(6):E1210–29.

    Article  CAS  PubMed  Google Scholar 

  7. Bramlage P, Pittrow D, Wittchen HU, Kirch W, Boehler S, Lehnert H, et al. Hypertension in overweight and obese primary care patients is highly prevalent and poorly controlled. Am J Hypertens. 2004;17(10):904–10.

    Article  PubMed  Google Scholar 

  8. Esler M, Julius S, Zweifler A, Randall O, Harburg E, Gardiner H, et al. Mild high-renin essential hypertension. Neurogenic human hypertension? N Engl J Med. 1977;296(8):405–11.

    Article  CAS  PubMed  Google Scholar 

  9. Julius S, Pascual AV, Sannerstedt R, Mitchell C. Relationship between cardiac output and peripheral resistance in borderline hypertension. Circulation. 1971;43(3):382–90.

    Article  CAS  PubMed  Google Scholar 

  10. Heagerty AM, Heerkens EH, Izzard AS. Small artery structure and function in hypertension. J Cell Mol Med. 2010;14(5):1037–43.

    PubMed  PubMed Central  Google Scholar 

  11. Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell. 2014;156(1–2):20–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ouwens DM, Sell H, Greulich S, Eckel J. The role of epicardial and perivascular adipose tissue in the pathophysiology of cardiovascular disease. J Cell Mol Med. 2010;14(9):2223–34.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Yudkin JS, Eringa E, Stehouwer CD. “Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet. 2005;365(9473):1817–20.

    Article  PubMed  Google Scholar 

  14. Aghamohammadzadeh R, Withers S, Lynch F, Greenstein A, Malik R, Heagerty A. Perivascular adipose tissue from human systemic and coronary vessels: the emergence of a new pharmacotherapeutic target. Br J Pharmacol. 2012;165(3):670–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G. Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes. 2003;52(7):1779–85.

    Article  CAS  PubMed  Google Scholar 

  16. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev. 2005;26(3):439–51.

    Article  CAS  PubMed  Google Scholar 

  17. Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O, Jeziorska M, et al. Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation. 2009;119(12):1661–70.

    Article  CAS  PubMed  Google Scholar 

  18. Baylie R, Ahmed M, Bonev AD, Hill-Eubanks DC, Heppner TJ, Nelson MT, et al. Lack of direct effect of adiponectin on vascular smooth muscle cell BKCa channels or Ca(2+) signaling in the regulation of small artery pressure-induced constriction. Phys Rep. 2017;5(16)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Nakagawa K, Higashi Y, Sasaki S, Oshima T, Matsuura H, Chayama K. Leptin causes vasodilation in humans. Hypertens Res Off J Japan Soc Hypertens. 2002;25(2):161–5.

    Article  CAS  Google Scholar 

  20. Sahin AS, Bariskaner H. The mechanisms of vasorelaxant effect of leptin on isolated rabbit aorta. Fundam Clin Pharmacol. 2007;21(6):595–600.

    Article  CAS  PubMed  Google Scholar 

  21. Kimura K, Tsuda K, Baba A, Kawabe T, Boh-oka S, Ibata M, et al. Involvement of nitric oxide in endothelium-dependent arterial relaxation by leptin. Biochem Biophys Res Commun. 2000;273(2):745–9.

    Article  CAS  PubMed  Google Scholar 

  22. Guzik TJ, Marvar PJ, Czesnikiewicz-Guzik M, Korbut R. Perivascular adipose tissue as a messenger of the brain-vessel axis: role in vascular inflammation and dysfunction. J Physiol Pharmacol Off J Pol Physiol Soc. 2007;58(4):591–610.

    CAS  Google Scholar 

  23. Frühbeck G. Pivotal role of nitric oxide in the control of blood pressure after leptin administration. Diabetes. 1999;48(4):903–8.

    Article  PubMed  Google Scholar 

  24. Knudson JD, Dincer UD, Zhang C, Swafford AN Jr, Koshida R, Picchi A, et al. Leptin receptors are expressed in coronary arteries, and hyperleptinemia causes significant coronary endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2005;289(1):H48–56.

    Article  CAS  PubMed  Google Scholar 

  25. Payne GA, Borbouse L, Kumar S, Neeb Z, Alloosh M, Sturek M, et al. Epicardial perivascular adipose-derived leptin exacerbates coronary endothelial dysfunction in metabolic syndrome via a protein kinase C-beta pathway. Arterioscler Thromb Vasc Biol. 2010;30(9):1711–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Shek EW, Brands MW, Hall JE. Chronic leptin infusion increases arterial pressure. Hypertension. 1998;31(1 Pt 2):409–14.

    Article  CAS  PubMed  Google Scholar 

  27. Fukai N, Yoshimoto T, Sugiyama T, Ozawa N, Sato R, Shichiri M, et al. Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues. Am J Physiol Endocrinol Metab. 2005;288(1):E56–62.

    Article  CAS  PubMed  Google Scholar 

  28. Nuki C, Kawasaki H, Kitamura K, Takenaga M, Kangawa K, Eto T, et al. Vasodilator effect of adrenomedullin and calcitonin gene-related peptide receptors in rat mesenteric vascular beds. Biochem Biophys Res Commun. 1993;196(1):245–51.

    Article  CAS  PubMed  Google Scholar 

  29. Nagaya N, Nishikimi T, Uematsu M, Satoh T, Oya H, Kyotani S, et al. Haemodynamic and hormonal effects of adrenomedullin in patients with pulmonary hypertension. Heart. 2000;84(6):653–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yoshimoto T, Gochou N, Fukai N, Sugiyama T, Shichiri M, Hirata Y. Adrenomedullin inhibits angiotensin II-induced oxidative stress and gene expression in rat endothelial cells. Hypertens Res Off J Japan Soc Hypertens. 2005;28(2):165–72.

    Article  CAS  Google Scholar 

  31. Shyu KG, Lien LM, Wang BW, Kuan P, Chang H. Resistin contributes to neointimal formation via oxidative stress after vascular injury. Clin Sci. 2011;120(3):121–9.

    Article  CAS  Google Scholar 

  32. Verhagen SN, Visseren FL. Perivascular adipose tissue as a cause of atherosclerosis. Atherosclerosis. 2011;214(1):3–10.

    Article  CAS  PubMed  Google Scholar 

  33. Shi Y, O’Brien JE, Fard A, Mannion JD, Wang D, Zalewski A. Adventitial myofibroblasts contribute to neointimal formation in injured porcine coronary arteries. Circulation. 1996;94(7):1655–64.

    Article  CAS  PubMed  Google Scholar 

  34. Booth RF, Martin JF, Honey AC, Hassall DG, Beesley JE, Moncada S. Rapid development of atherosclerotic lesions in the rabbit carotid artery induced by perivascular manipulation. Atherosclerosis. 1989;76(2–3):257–68.

    Article  CAS  PubMed  Google Scholar 

  35. Pagano PJ, Clark JK, Cifuentes-Pagano ME, Clark SM, Callis GM, Quinn MT. Localization of a constitutively active, phagocyte-like NADPH oxidase in rabbit aortic adventitia: enhancement by angiotensin II. Proc Natl Acad Sci U S A. 1997;94(26):14483–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang HD, Pagano PJ, Du Y, Cayatte AJ, Quinn MT, Brecher P, et al. Superoxide anion from the adventitia of the rat thoracic aorta inactivates nitric oxide. Circ Res. 1998;82(7):810–8.

    Article  CAS  PubMed  Google Scholar 

  37. Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, et al. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation. 2003;108(20):2460–6.

    Article  PubMed  Google Scholar 

  38. de Vos AM, Prokop M, Roos CJ, Meijs MF, van der Schouw YT, Rutten A, et al. Peri-coronary epicardial adipose tissue is related to cardiovascular risk factors and coronary artery calcification in post-menopausal women. Eur Heart J. 2008;29(6):777–83.

    Article  PubMed  Google Scholar 

  39. Antonopoulos AS, Sanna F, Sabharwal N, Thomas S, Oikonomou EK, Herdman L, et al. Detecting human coronary inflammation by imaging perivascular fat. Sci Transl Med. 2017;9(398).

    Article  PubMed  CAS  Google Scholar 

  40. Verhagen SN, Vink A, van der Graaf Y, Visseren FL. Coronary perivascular adipose tissue characteristics are related to atherosclerotic plaque size and composition. A post-mortem study. Atherosclerosis. 2012;225(1):99–104.

    Article  CAS  PubMed  Google Scholar 

  41. Henrichot E, Juge-Aubry CE, Pernin A, Pache JC, Velebit V, Dayer JM, et al. Production of chemokines by perivascular adipose tissue: a role in the pathogenesis of atherosclerosis? Arterioscler Thromb Vasc Biol. 2005;25(12):2594–9.

    Article  CAS  PubMed  Google Scholar 

  42. Ishikawa Y, Akasaka Y, Ito K, Akishima Y, Kimura M, Kiguchi H, et al. Significance of anatomical properties of myocardial bridge on atherosclerosis evolution in the left anterior descending coronary artery. Atherosclerosis. 2006;186(2):380–9.

    Article  CAS  PubMed  Google Scholar 

  43. Ohman MK, Luo W, Wang H, Guo C, Abdallah W, Russo HM, et al. Perivascular visceral adipose tissue induces atherosclerosis in apolipoprotein E deficient mice. Atherosclerosis. 2011;219(1):33–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Chang L, Villacorta L, Li R, Hamblin M, Xu W, Dou C, et al. Loss of perivascular adipose tissue on peroxisome proliferator-activated receptor-gamma deletion in smooth muscle cells impairs intravascular thermoregulation and enhances atherosclerosis. Circulation. 2012;126(9):1067–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Brown NK, Zhou Z, Zhang J, Zeng R, Wu J, Eitzman DT, et al. Perivascular adipose tissue in vascular function and disease: a review of current research and animal models. Arterioscler Thromb Vasc Biol. 2014;34(8):1621–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Dawkins MJ, Scopes JW. Non-shivering thermogenesis and brown adipose tissue in the human new-born infant. Nature. 1965;206(980):201–2.

    Article  CAS  PubMed  Google Scholar 

  47. Galvez B, de Castro J, Herold D, Dubrovska G, Arribas S, Gonzalez MC, et al. Perivascular adipose tissue and mesenteric vascular function in spontaneously hypertensive rats. Arterioscler Thromb Vasc Biol. 2006;26(6):1297–302.

    Article  CAS  PubMed  Google Scholar 

  48. Lee RM, Lu C, Su LY, Gao YJ. Endothelium-dependent relaxation factor released by perivascular adipose tissue. J Hypertens. 2009;27(4):782–90.

    Article  CAS  PubMed  Google Scholar 

  49. Ruan CC, Zhu DL, Chen QZ, Chen J, Guo SJ, Li XD, et al. Perivascular adipose tissue-derived complement 3 is required for adventitial fibroblast functions and adventitial remodeling in deoxycorticosterone acetate-salt hypertensive rats. Arterioscler Thromb Vasc Biol. 2010;30(12):2568–74.

    Article  CAS  PubMed  Google Scholar 

  50. Galvez-Prieto B, Somoza B, Gil-Ortega M, Garcia-Prieto CF, de Las Heras AI, Gonzalez MC, et al. Anticontractile effect of perivascular adipose tissue and leptin are reduced in hypertension. Front Pharmacol. 2012;3:103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Payne RA, Wilkinson IB, Webb DJ. Arterial stiffness and hypertension: emerging concepts. Hypertension. 2010;55(1):9–14.

    Article  CAS  PubMed  Google Scholar 

  52. Fleenor BS, Eng JS, Sindler AL, Pham BT, Kloor JD, Seals DR. Superoxide signaling in perivascular adipose tissue promotes age-related artery stiffness. Aging Cell. 2014;13(3):576–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Hirsch J, Batchelor B. Adipose tissue cellularity in human obesity. Clin Endocrinol Metab. 1976;5(2):299–311.

    Article  CAS  PubMed  Google Scholar 

  54. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Szasz T, Bomfim GF, Webb RC. The influence of perivascular adipose tissue on vascular homeostasis. Vasc Health Risk Manag. 2013;9:105–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Karalis KP, Giannogonas P, Kodela E, Koutmani Y, Zoumakis M, Teli T. Mechanisms of obesity and related pathology: linking immune responses to metabolic stress. FEBS J. 2009;276(20):5747–54.

    Article  CAS  PubMed  Google Scholar 

  57. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112(12):1821–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Lehman SJ, Massaro JM, Schlett CL, O’Donnell CJ, Hoffmann U, Fox CS. Peri-aortic fat, cardiovascular disease risk factors, and aortic calcification: the Framingham Heart Study. Atherosclerosis. 2010;210(2):656–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Withers SB, Agabiti-Rosei C, Livingstone DM, Little MC, Aslam R, Malik RA, et al. Macrophage activation is responsible for loss of anticontractile function in inflamed perivascular fat. Arterioscler Thromb Vasc Biol. 2011;31(4):908–13.

    Article  CAS  PubMed  Google Scholar 

  60. Ketonen J, Shi J, Martonen E, Mervaala E. Periadventitial adipose tissue promotes endothelial dysfunction via oxidative stress in diet-induced obese C57Bl/6 mice. Circ J. 2010;74(7):1479–87.

    Article  CAS  PubMed  Google Scholar 

  61. 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.

    Article  CAS  PubMed  Google Scholar 

  62. da Silva AA, do Carmo J, Dubinion J, Hall JE. The role of the sympathetic nervous system in obesity-related hypertension. Curr Hypertens Rep. 2009;11(3):206–11.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006;6(10):772–83.

    Article  CAS  PubMed  Google Scholar 

  64. Barandier C, Montani JP, Yang Z. Mature adipocytes and perivascular adipose tissue stimulate vascular smooth muscle cell proliferation: effects of aging and obesity. Am J Physiol Heart Circ Physiol. 2005;289(5):H1807–13.

    Article  CAS  PubMed  Google Scholar 

  65. Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem. 2002;277(29):25863–6.

    Article  CAS  PubMed  Google Scholar 

  66. Wang P, Xu TY, Guan YF, Su DF, Fan GR, Miao CY. Perivascular adipose tissue-derived visfatin is a vascular smooth muscle cell growth factor: role of nicotinamide mononucleotide. Cardiovasc Res. 2009;81(2):370–80.

    Article  CAS  PubMed  Google Scholar 

  67. Lamers D, Schlich R, Greulich S, Sasson S, Sell H, Eckel J. Oleic acid and adipokines synergize in inducing proliferation and inflammatory signalling in human vascular smooth muscle cells. J Cell Mol Med. 2011;15(5):1177–88.

    Article  CAS  PubMed  Google Scholar 

  68. Okon EB, Chung AW, Rauniyar P, Padilla E, Tejerina T, McManus BM, et al. Compromised arterial function in human type 2 diabetic patients. Diabetes. 2005;54(8):2415–23.

    Article  CAS  PubMed  Google Scholar 

  69. Meijer RI, Serne EH, Smulders YM, van Hinsbergh VW, Yudkin JS, Eringa EC. Perivascular adipose tissue and its role in type 2 diabetes and cardiovascular disease. Curr Diab Rep. 2011;11(3):211–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Eringa EC, Bakker W, van Hinsbergh VW. Paracrine regulation of vascular tone, inflammation and insulin sensitivity by perivascular adipose tissue. Vasc Pharmacol. 2012;56(5–6):204–9.

    Article  CAS  Google Scholar 

  71. Meijer RI, Bakker W, Alta CL, Sipkema P, Yudkin JS, Viollet B, et al. Perivascular adipose tissue control of insulin-induced vasoreactivity in muscle is impaired in db/db mice. Diabetes. 2013;62(2):590–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Bradley EA, Eringa EC, Stehouwer CD, Korstjens I, van Nieuw Amerongen GP, Musters R, et al. Activation of AMP-activated protein kinase by 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside in the muscle microcirculation increases nitric oxide synthesis and microvascular perfusion. Arterioscler Thromb Vasc Biol. 2010;30(6):1137–42.

    Article  CAS  PubMed  Google Scholar 

  73. Eringa EC, Stehouwer CD, Walburg K, Clark AD, van Nieuw Amerongen GP, Westerhof N, et al. Physiological concentrations of insulin induce endothelin-dependent vasoconstriction of skeletal muscle resistance arteries in the presence of tumor necrosis factor-alpha dependence on c-Jun N-terminal kinase. Arterioscler Thromb Vasc Biol. 2006;26(2):274–80.

    Article  CAS  PubMed  Google Scholar 

  74. Wallis MG, Wheatley CM, Rattigan S, Barrett EJ, Clark AD, Clark MG. Insulin-mediated hemodynamic changes are impaired in muscle of Zucker obese rats. Diabetes. 2002;51(12):3492–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Adam S. Greenstein .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Javed, S., Alakrawi, M., Greenstein, A.S. (2019). Perivascular Adipose Tissue. In: Touyz, R., Delles, C. (eds) Textbook of Vascular Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-16481-2_23

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-16481-2_23

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-16480-5

  • Online ISBN: 978-3-030-16481-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics