Top

Published in:

01-11-2016 | Hypertension and Obesity (E Reisin, Section Editor)

A Clinical Perspective: Contribution of Dysfunctional Perivascular Adipose Tissue (PVAT) to Cardiovascular Risk

Authors: Xiaoming Lian, Maik Gollasch

Published in: Current Hypertension Reports | Issue 11/2016

Abstract

Perivascular adipose tissue (PVAT) is now recognized as an important paracrine organ influencing the homeostasis of the vessel wall, regional blood flow and peripheral arterial resistance. There is remarkable phenotypic variability and plasticity of PVAT among various vascular beds, exhibiting phenotypes from white to brown and beige adipocytes. PVAT dysfunction is characterized by disturbed secretion of various adipokines, which, together with endothelial dysfunction, contribute to hypertension and cardiovascular disease (CVD). This brief review describes our current knowledge on PVAT in health and cardiovascular disease, with a special focus on different phenotypes and signaling pathways in adipocytes of PVAT associated with hypertension, obesity and cardiovascular disorders.

Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of Obesity Among Adults and Youth: United States, 2011-2014. NCHS Data Brief. 2015(219):1–8.

Gelber RP, Gaziano JM, Orav EJ, Manson JE, Buring JE, Kurth T. Measures of obesity and cardiovascular risk among men and women. J Am Coll Cardiol. 2008;52(8):605–15. doi:10.1016/j.jacc.2008.03.066.CrossRefPubMedPubMedCentral

Writing Group M, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38–360. doi:10.1161/CIR.0000000000000350.CrossRef

Scherer PE. Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes. 2006;55(6):1537–45. doi:10.2337/db06-0263.CrossRefPubMed

Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res. 2005;96(9):939–49. doi:10.1161/01.RES.0000163635.62927.34.CrossRefPubMed

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. doi:10.1016/j.atherosclerosis.2010.01.007.CrossRefPubMedPubMedCentral

Dupont J, Pollet-Villard X, Reverchon M, Mellouk N, Levy R. Adipokines in human reproduction. Horm Mol Biol Clin Investig. 2015;24(1):11–24. doi:10.1515/hmbci-2015-0034.PubMed

Abraham TM, Pedley A, Massaro JM, Hoffmann U, Fox CS. Association between visceral and subcutaneous adipose depots and incident cardiovascular disease risk factors. Circulation. 2015;132(17):1639–47. doi:10.1161/CIRCULATIONAHA.114.015000.CrossRefPubMedPubMedCentral

Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116(1):39–48. doi:10.1161/CIRCULATIONAHA.106.675355.CrossRefPubMed

10.

McLaughlin T, Lamendola C, Liu A, Abbasi F. Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. J Clin Endocrinol Metab. 2011;96(11):E1756–60. doi:10.1210/jc.2011-0615.CrossRefPubMedPubMedCentral

11.

Katzmarzyk PT, Mire E, Bouchard C. Abdominal obesity and mortality: The Pennington Center Longitudinal Study. Nutr Diabetes. 2012;2, e42. doi:10.1038/nutd.2012.15.CrossRefPubMedPubMedCentral

12.

Chatterjee TK, Stoll LL, Denning GM, Harrelson A, Blomkalns AL, Idelman G, et al. Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding. Circ Res. 2009;104(4):541–9. doi:10.1161/CIRCRESAHA.108.182998.CrossRefPubMedPubMedCentral

13.

Lee YC, Chang HH, Chiang CL, Liu CH, Yeh JI, Chen MF, et al. Role of perivascular adipose tissue-derived methyl palmitate in vascular tone regulation and pathogenesis of hypertension. Circulation. 2011;124(10):1160–71. doi:10.1161/CIRCULATIONAHA.111.027375.CrossRefPubMed

14.

Rittig K, Dolderer JH, Balletshofer B, Machann J, Schick F, Meile T, et al. The secretion pattern of perivascular fat cells is different from that of subcutaneous and visceral fat cells. Diabetologia. 2012;55(5):1514–25. doi:10.1007/s00125-012-2481-9.CrossRefPubMed

15.

Ozen G, Daci A, Norel X, Topal G. Human perivascular adipose tissue dysfunction as a cause of vascular disease: Focus on vascular tone and wall remodeling. Eur J Pharmacol. 2015;766:16–24. doi:10.1016/j.ejphar.2015.09.012.CrossRefPubMed

16.

Kagota S, Iwata S, Maruyama K, Wakuda H, Shinozuka K. Functional relationship between arterial tissue and perivascular adipose tissue in metabolic syndrome. Yakugaku Zasshi. 2016;136(5):693–7. doi:10.1248/yakushi.15-00262-2.CrossRefPubMed

17.

Nakamura K, Fuster JJ, Walsh K. Adipokines: a link between obesity and cardiovascular disease. J Cardiol. 2014;63(4):250–9. doi:10.1016/j.jjcc.2013.11.006.CrossRefPubMed

18.

Mahabadi AA, Reinsch N, Lehmann N, Altenbernd J, Kalsch H, Seibel RM, et al. Association of pericoronary fat volume with atherosclerotic plaque burden in the underlying coronary artery: a segment analysis. Atherosclerosis. 2010;211(1):195–9. doi:10.1016/j.atherosclerosis.2010.02.013.CrossRefPubMed

19.

Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85–97. doi:10.1038/nri2921.CrossRefPubMedPubMedCentral

20.

Mohammed MM, Myers DS, Sofola OA, Hainsworth R, Drinkhill MJ. Vasodilator effects of leptin on canine isolated mesenteric arteries and veins. Clin Exp Pharmacol Physiol. 2007;34(8):771–4. doi:10.1111/j.1440-1681.2007.04648.x.CrossRefPubMed

21.

Szasz T, Webb RC. Perivascular adipose tissue: more than just structural support. Clin Sci (Lond). 2012;122(1):1–12. doi:10.1042/CS20110151.CrossRef

22.

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. doi:10.1093/cvr/cvn288.CrossRefPubMed

23.

Shields KJ, Stolz D, Watkins SC, Ahearn JM. Complement proteins C3 and C4 bind to collagen and elastin in the vascular wall: a potential role in vascular stiffness and atherosclerosis. Clin Trans Sci. 2011;4(3):146–52. doi:10.1111/j.1752-8062.2011.00304.x.CrossRef

24.

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. doi:10.1161/01.ATV.0000220381.40739.dd.CrossRefPubMed

25.

Knudson JD, Dincer UD, Zhang C, Swafford Jr AN, 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. doi:10.1152/ajpheart.01159.2004.CrossRefPubMed

26.

Van de Voorde J, Boydens C, Pauwels B, Decaluwe K. Perivascular adipose tissue, inflammation and vascular dysfunction in obesity. Curr Vasc Pharmacol. 2014;12(3):403–11.CrossRef

27.

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.CrossRefPubMed

28.

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. doi:10.1161/ATVBAHA.110.210070.CrossRefPubMedPubMedCentral

29.

Galvez-Prieto B, Dubrovska G, Cano MV, Delgado M, Aranguez I, Gonzalez MC, et al. A reduction in the amount and anti-contractile effect of periadventitial mesenteric adipose tissue precedes hypertension development in spontaneously hypertensive rats. Hypertens Res. 2008;31(7):1415–23. doi:10.1291/hypres.31.1415.CrossRefPubMed

30.

Chang J, Li Y, Huang Y, Lam KS, Hoo RL, Wong WT, et al. Adiponectin prevents diabetic premature senescence of endothelial progenitor cells and promotes endothelial repair by suppressing the p38 MAP kinase/p16INK4A signaling pathway. Diabetes. 2010;59(11):2949–59. doi:10.2337/db10-0582.CrossRefPubMedPubMedCentral

31.

Zhang P, Wang Y, Fan Y, Tang Z, Wang N. Overexpression of adiponectin receptors potentiates the antiinflammatory action of subeffective dose of globular adiponectin in vascular endothelial cells. Arterioscler Thromb Vasc Biol. 2009;29(1):67–74. doi:10.1161/ATVBAHA.108.178061.CrossRefPubMed

32.

Hulsmans M, Van Dooren E, Mathieu C, Holvoet P. Decrease of miR-146b-5p in monocytes during obesity is associated with loss of the anti-inflammatory but not insulin signaling action of adiponectin. PLoS One. 2012;7(2), e32794. doi:10.1371/journal.pone.0032794.CrossRefPubMedPubMedCentral

33.

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.CrossRefPubMed

34.

Peri-Okonny PA, Ayers C, Maalouf N, Das SR, de Lemos JA, Berry JD, et al. Adiponectin protects against incident hypertension independent of body fat distribution: observations from the Dallas Heart Study. Diabetes Metab Res Rev. 2016. doi:10.1002/dmrr.2840.PubMed

35.

Xu A, Vanhoutte PM. Adiponectin and adipocyte fatty acid binding protein in the pathogenesis of cardiovascular disease. Am J Physiol Heart Circ Physiol. 2012;302(6):H1231–40. doi:10.1152/ajpheart.00765.2011.CrossRefPubMed

36.

Sarvottam K, Magan D, Yadav RK, Mehta N, Mahapatra SC. Adiponectin, interleukin-6, and cardiovascular disease risk factors are modified by a short-term yoga-based lifestyle intervention in overweight and obese men. J Altern Complement Med. 2013;19(5):397–402. doi:10.1089/acm.2012.0086.CrossRefPubMed

37.

Goldstein BJ, Scalia RG, Ma XL. Protective vascular and myocardial effects of adiponectin. Nat Clin Pract Cardiovasc Med. 2009;6(1):27–35. doi:10.1038/ncpcardio1398.CrossRefPubMed

38.

Morita Y, Maeda K, Kondo T, Ishii H, Matsudaira K, Okumura N, et al. Impact of adiponectin and leptin on long-term adverse events in Japanese patients with acute myocardial infarction. Results from the Nagoya Acute Myocardial Infarction Study (NAMIS). Circ J. 2013;77(11):2778–85.CrossRefPubMed

39.

Wu ZJ, Cheng YJ, Gu WJ, Aung LH. Adiponectin is associated with increased mortality in patients with already established cardiovascular disease: a systematic review and meta-analysis. Metabolism. 2014;63(9):1157–66. doi:10.1016/j.metabol.2014.05.001.CrossRefPubMed

40.

Cheng KK, Lam KS, Wang Y, Huang Y, Carling D, Wu D, et al. Adiponectin-induced endothelial nitric oxide synthase activation and nitric oxide production are mediated by APPL1 in endothelial cells. Diabetes. 2007;56(5):1387–94. doi:10.2337/db06-1580.CrossRefPubMed

41.

Margaritis M, Antonopoulos AS, Digby J, Lee R, Reilly S, Coutinho P, et al. Interactions between vascular wall and perivascular adipose tissue reveal novel roles for adiponectin in the regulation of endothelial nitric oxide synthase function in human vessels. Circulation. 2013;127(22):2209–21. doi:10.1161/CIRCULATIONAHA.112.001133.CrossRefPubMed

42.

Yu L, Tu Q, Han Q, Zhang L, Sui L, Zheng L, et al. Adiponectin regulates bone marrow mesenchymal stem cell niche through a unique signal transduction pathway: an approach for treating bone disease in diabetes. Stem Cells. 2015;33(1):240–52. doi:10.1002/stem.1844.CrossRefPubMedPubMedCentral

43.

Rocha VZ, Folco EJ, Ozdemir C, Sheikine Y, Christen T, Sukhova GK, et al. CXCR3 controls T-cell accumulation in fat inflammation. Arterioscler Thromb Vasc Biol. 2014;34(7):1374–81. doi:10.1161/ATVBAHA.113.303133.CrossRefPubMedPubMedCentral

44.

van Stijn CM, Kim J, Barish GD, Tietge UJ, Tangirala RK. Adiponectin expression protects against angiotensin II-mediated inflammation and accelerated atherosclerosis. PLoS One. 2014;9(1), e86404. doi:10.1371/journal.pone.0086404.CrossRefPubMedPubMedCentral

45.

Guo J, Bian Y, Bai R, Li H, Fu M, Xiao C. Globular adiponectin attenuates myocardial ischemia/reperfusion injury by upregulating endoplasmic reticulum Ca(2)(+)-ATPase activity and inhibiting endoplasmic reticulum stress. J Cardiovasc Pharmacol. 2013;62(2):143–53. doi:10.1097/FJC.0b013e31829521af.CrossRefPubMed

46.

Cao T, Gao Z, Gu L, Chen M, Yang B, Cao K, et al. AdipoR1/APPL1 potentiates the protective effects of globular adiponectin on angiotensin II-induced cardiac hypertrophy and fibrosis in neonatal rat atrial myocytes and fibroblasts. PLoS One. 2014;9(8), e103793. doi:10.1371/journal.pone.0103793.CrossRefPubMedPubMedCentral

47.

Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395(6704):763–70. doi:10.1038/27376.CrossRefPubMed

48.

Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995;269(5223):543–6.CrossRefPubMed

49.

Myers Jr MG, Leibel RL, Seeley RJ, Schwartz MW. Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol Metab. 2010;21(11):643–51. doi:10.1016/j.tem.2010.08.002.CrossRefPubMedPubMedCentral

50.

Huby AC, Otvos Jr L. Belin de Chantemele EJ. Leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in obese female mice. Hypertension. 2016;67(5):1020–8. doi:10.1161/HYPERTENSIONAHA.115.06642.CrossRefPubMedPubMedCentral

51.

Beltowski J. Leptin and atherosclerosis. Atherosclerosis. 2006;189(1):47–60. doi:10.1016/j.atherosclerosis.2006.03.003.CrossRefPubMed

52.

Martin SS, Qasim AN, Rader DJ, Reilly MP. C-reactive protein modifies the association of plasma leptin with coronary calcium in asymptomatic overweight individuals. Obesity (Silver Spring). 2012;20(4):856–61. doi:10.1038/oby.2011.164.CrossRef

53.

Bickel C, Schnabel RB, Zeller T, Lackner KJ, Rupprecht HJ, Blankenberg S et al. Predictors of leptin concentration and association with cardiovascular risk in patients with coronary artery disease: results from the AtheroGene study. Biomarkers. 2016:1–9. doi:10.3109/1354750X.2015.1130745.

54.

Amrock SM, Weitzman M. Effect of increased leptin and C-reactive protein levels on mortality: results from the National Health and Nutrition Examination Survey. Atherosclerosis. 2014;236(1):1–6. doi:10.1016/j.atherosclerosis.2014.06.009.CrossRefPubMedPubMedCentral

55.

Petrini S, Neri T, Lombardi S, Cordazzo C, Balia C, Scalise V, et al. Leptin induces the generation of procoagulant, tissue factor bearing microparticles by human peripheral blood mononuclear cells. Biochim Biophys Acta. 2016;1860(6):1354–61. doi:10.1016/j.bbagen.2016.03.029.CrossRefPubMed

56.

Zlokovic BV, Jovanovic S, Miao W, Samara S, Verma S, Farrell CL. Differential regulation of leptin transport by the choroid plexus and blood-brain barrier and high affinity transport systems for entry into hypothalamus and across the blood-cerebrospinal fluid barrier. Endocrinology. 2000;141(4):1434–41. doi:10.1210/endo.141.4.7435.PubMed

57.

Benkhoff S, Loot AE, Pierson I, Sturza A, Kohlstedt K, Fleming I, et al. Leptin potentiates endothelium-dependent relaxation by inducing endothelial expression of neuronal NO synthase. Arterioscler Thromb Vasc Biol. 2012;32(7):1605–12. doi:10.1161/ATVBAHA.112.251140.CrossRefPubMed

58.

Matsumoto T, Noguchi E, Ishida K, Nakayama N, Kobayashi T, Kamata K. Cilostazol improves endothelial dysfunction by increasing endothelium-derived hyperpolarizing factor response in mesenteric arteries from Type 2 diabetic rats. Eur J Pharmacol. 2008;599(1-3):102–9. doi:10.1016/j.ejphar.2008.10.006.CrossRefPubMed

59.

Beltowski J, Wojcicka G, Jamroz-Wisniewska A. Role of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) in the regulation of blood pressure by leptin in lean and obese rats. Life Sci. 2006;79(1):63–71. doi:10.1016/j.lfs.2005.12.041.CrossRefPubMed

60.

Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, et al. Leptin regulates bone formation via the sympathetic nervous system. Cell. 2002;111(3):305–17.CrossRefPubMed

61.

Wang J, Wang H, Luo W, Guo C, Wang J, Chen YE, et al. Leptin-induced endothelial dysfunction is mediated by sympathetic nervous system activity. J Am Heart Assoc. 2013;2(5), e000299. doi:10.1161/JAHA.113.000299.CrossRefPubMedPubMedCentral

62.

Dubrovska G, Verlohren S, Luft FC, Gollasch M. Mechanisms of ADRF release from rat aortic adventitial adipose tissue. Am J Physiol Heart Circ Physiol. 2004;286(3):H1107–13. doi:10.1152/ajpheart.00656.2003.CrossRefPubMed

63.

Gollasch M. Vasodilator signals from perivascular adipose tissue. Br J Pharmacol. 2012;165(3):633–42. doi:10.1111/j.1476-5381.2011.01430.x.CrossRefPubMedPubMedCentral

64.

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. doi:10.1161/CIRCULATIONAHA.108.821181.CrossRefPubMed

65.

DeBoer MD. Obesity, systemic inflammation, and increased risk for cardiovascular disease and diabetes among adolescents: a need for screening tools to target interventions. Nutrition. 2013;29(2):379–86. doi:10.1016/j.nut.2012.07.003.CrossRefPubMed

66.

Noonan DM, De Lerma BA, Vannini N, Mortara L, Albini A. Inflammation, inflammatory cells and angiogenesis: decisions and indecisions. Cancer Metastasis Rev. 2008;27(1):31–40. doi:10.1007/s10555-007-9108-5.CrossRefPubMed

67.

Nguyen Dinh Cat A, Briones AM, Callera GE, Yogi A, He Y, Montezano AC, et al. Adipocyte-derived factors regulate vascular smooth muscle cells through mineralocorticoid and glucocorticoid receptors. Hypertension. 2011;58(3):479–88. doi:10.1161/HYPERTENSIONAHA.110.168872.CrossRefPubMed

68.

Galvez-Prieto B, Bolbrinker J, Stucchi P, de Las Heras AI, Merino B, Arribas S, et al. Comparative expression analysis of the renin-angiotensin system components between white and brown perivascular adipose tissue. J Endocrinol. 2008;197(1):55–64. doi:10.1677/JOE-07-0284.CrossRefPubMed

69.

Lee RM, Lu C, Su LY, Gao YJ. Endothelium-dependent relaxation factor released by perivascular adipose tissue. J Hypertens. 2009;27(4):782–90. doi:10.1097/HJH.0b013e328324ed86.CrossRefPubMed

70.

Gao YJ, Takemori K, Su LY, An WS, Lu C, Sharma AM, et al. Perivascular adipose tissue promotes vasoconstriction: the role of superoxide anion. Cardiovasc Res. 2006;71(2):363–73. doi:10.1016/j.cardiores.2006.03.013.CrossRefPubMed

71.

Tano JY, Schleifenbaum J, Gollasch M. Perivascular adipose tissue, potassium channels, and vascular dysfunction. Arterioscler Thromb Vasc Biol. 2014;34(9):1827–30. doi:10.1161/ATVBAHA.114.303032.CrossRefPubMed

72.

Zavaritskaya O, Zhuravleva N, Schleifenbaum J, Gloe T, Devermann L, Kluge R, et al. Role of KCNQ channels in skeletal muscle arteries and periadventitial vascular dysfunction. Hypertension. 2013;61(1):151–9. doi:10.1161/HYPERTENSIONAHA.112.197566.CrossRefPubMed

73.

Gollasch M, Dubrovska G. Paracrine role for periadventitial adipose tissue in the regulation of arterial tone. Trends Pharmacol Sci. 2004;25(12):647–53. doi:10.1016/j.tips.2004.10.005.CrossRefPubMed

74.

Hausman DB, DiGirolamo M, Bartness TJ, Hausman GJ, Martin RJ. The biology of white adipocyte proliferation. Obes Rev. 2001;2(4):239–54.CrossRefPubMed

75.

Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007;293(2):E444–52. doi:10.1152/ajpendo.00691.2006.CrossRefPubMed

76.

Fitzgibbons TP, Kogan S, Aouadi M, Hendricks GM, Straubhaar J, Czech MP. Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation. Am J Physiol Heart Circ Physiol. 2011;301(4):H1425–37. doi:10.1152/ajpheart.00376.2011.CrossRefPubMedPubMedCentral

77.

Chatterjee TK, Aronow BJ, Tong WS, Manka D, Tang Y, Bogdanov VY, et al. Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis. Physiol Genomics. 2013;45(16):697–709. doi:10.1152/physiolgenomics.00042.2013.CrossRefPubMedPubMedCentral

78.

Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012;150(2):366–76. doi:10.1016/j.cell.2012.05.016.CrossRefPubMedPubMedCentral

79.

Richard D, Monge-Roffarello B, Chechi K, Labbe SM, Turcotte EE. Control and physiological determinants of sympathetically mediated brown adipose tissue thermogenesis. Front Endocrinol (Lausanne). 2012;3:36. doi:10.3389/fendo.2012.00036.

80.

Sacks HS, Fain JN, Holman B, Cheema P, Chary A, Parks F, et al. Uncoupling protein-1 and related messenger ribonucleic acids in human epicardial and other adipose tissues: epicardial fat functioning as brown fat. J Clin Endocrinol Metab. 2009;94(9):3611–5. doi:10.1210/jc.2009-0571.CrossRefPubMed

81.

Bartelt A, Heeren J. The holy grail of metabolic disease: brown adipose tissue. Curr Opin Lipidol. 2012;23(3):190–5. doi:10.1097/MOL.0b013e328352dcef.CrossRefPubMed

82.

Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360(15):1509–17. doi:10.1056/NEJMoa0810780.CrossRefPubMedPubMedCentral

83.

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. doi:10.1161/CIRCULATIONAHA.112.104489.CrossRefPubMedPubMedCentral

84.

Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M, Kristiansen K, et al. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab. 2010;298(6):E1244–53. doi:10.1152/ajpendo.00600.2009.CrossRefPubMed

85.

Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem. 2010;285(10):7153–64. doi:10.1074/jbc.M109.053942.CrossRefPubMed

86.

Tran KV, Gealekman O, Frontini A, Zingaretti MC, Morroni M, Giordano A, et al. The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells. Cell Metab. 2012;15(2):222–9. doi:10.1016/j.cmet.2012.01.008.CrossRefPubMedPubMedCentral

87.

Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C, et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab. 2014;19(2):302–9. doi:10.1016/j.cmet.2013.12.017.CrossRefPubMed

88.

Hu R, He ML, Hu H, Yuan BX, Zang WJ, Lau CP, et al. Characterization of calcium signaling pathways in human preadipocytes. J Cell Physiol. 2009;220(3):765–70. doi:10.1002/jcp.21823.CrossRefPubMed

89.

Kassmann M, Harteneck C, Zhu Z, Nurnberg B, Tepel M, Gollasch M. Transient receptor potential vanilloid 1 (TRPV1), TRPV4, and the kidney. Acta Physiol (Oxf). 2013;207(3):546–64. doi:10.1111/apha.12051.CrossRef

90.

Palazzo E, Rossi F, de Novellis V, Maione S. Endogenous modulators of TRP channels. Curr Top Med Chem. 2013;13(3):398–407.CrossRefPubMed

91.

Shapovalov G, Lehen'kyi V, Skryma R, Prevarskaya N. TRP channels in cell survival and cell death in normal and transformed cells. Cell Calcium. 2011;50(3):295–302. doi:10.1016/j.ceca.2011.05.006.CrossRefPubMed

92.

Chen J, Li L, Li Y, Liang X, Sun Q, Yu H, et al. Activation of TRPV1 channel by dietary capsaicin improves visceral fat remodeling through connexin43-mediated Ca2+ influx. Cardiovasc Diabetol. 2015;14:22. doi:10.1186/s12933-015-0183-6.CrossRefPubMedPubMedCentral

93.

Baskaran P, Krishnan V, Ren J, Thyagarajan B. Capsaicin induces browning of white adipose tissue and counters obesity by activating TRPV1 channel-dependent mechanisms. Br J Pharmacol. 2016;173(15):2369–89. doi:10.1111/bph.13514.CrossRefPubMed

94.

Baboota RK, Singh DP, Sarma SM, Kaur J, Sandhir R, Boparai RK, et al. Capsaicin induces "brite" phenotype in differentiating 3T3-L1 preadipocytes. PLoS One. 2014;9(7), e103093. doi:10.1371/journal.pone.0103093.CrossRefPubMedPubMedCentral

95.

Bratz IN, Dick GM, Tune JD, Edwards JM, Neeb ZP, Dincer UD, et al. Impaired capsaicin-induced relaxation of coronary arteries in a porcine model of the metabolic syndrome. Am J Physiol Heart Circ Physiol. 2008;294(6):H2489–96. doi:10.1152/ajpheart.01191.2007.CrossRefPubMed

96.

Kark T, Bagi Z, Lizanecz E, Pasztor ET, Erdei N, Czikora A, et al. Tissue-specific regulation of microvascular diameter: opposite functional roles of neuronal and smooth muscle located vanilloid receptor-1. Mol Pharmacol. 2008;73(5):1405–12. doi:10.1124/mol.107.043323.CrossRefPubMed

97.

Cavanaugh DJ, Chesler AT, Jackson AC, Sigal YM, Yamanaka H, Grant R, et al. Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells. J Neurosci. 2011;31(13):5067–77. doi:10.1523/JNEUROSCI.6451-10.2011.CrossRefPubMedPubMedCentral

98.

Schleifenbaum J, Kassmann M, Szijarto IA, Hercule HC, Tano JY, Weinert S, et al. Stretch-activation of angiotensin II type 1a receptors contributes to the myogenic response of mouse mesenteric and renal arteries. Circ Res. 2014;115(2):263–72. doi:10.1161/CIRCRESAHA.115.302882.CrossRefPubMed

99.

Che H, Yue J, Tse HF, Li GR. Functional TRPV and TRPM channels in human preadipocytes. Pflugers Arch. 2014;466(5):947–59. doi:10.1007/s00424-013-1355-4.CrossRefPubMed

100.

Sun W, Uchida K, Takahashi N, Iwata Y, Wakabayashi S, Goto T, et al. Activation of TRPV2 negatively regulates the differentiation of mouse brown adipocytes. Pflugers Arch. 2016;468(9):1527–40. doi:10.1007/s00424-016-1846-1.CrossRefPubMed

101.

Lynch FM, Withers SB, Yao Z, Werner ME, Edwards G, Weston AH, et al. Perivascular adipose tissue-derived adiponectin activates BK(Ca) channels to induce anticontractile responses. Am J Physiol Heart Circ Physiol. 2013;304(6):H786–95. doi:10.1152/ajpheart.00697.2012.CrossRefPubMedPubMedCentral

102.

Weston AH, Egner I, Dong Y, Porter EL, Heagerty AM, Edwards G. Stimulated release of a hyperpolarizing factor (ADHF) from mesenteric artery perivascular adipose tissue: involvement of myocyte BKCa channels and adiponectin. Br J Pharmacol. 2013;169(7):1500–9. doi:10.1111/bph.12157.CrossRefPubMedPubMedCentral

103.

Fesus G, Dubrovska G, Gorzelniak K, Kluge R, Huang Y, Luft FC, et al. Adiponectin is a novel humoral vasodilator. Cardiovasc Res. 2007;75(4):719–27. doi:10.1016/j.cardiores.2007.05.025.CrossRefPubMed

104.

Iwabu M, Yamauchi T, Okada-Iwabu M, Sato K, Nakagawa T, Funata M, et al. Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Nature. 2010;464(7293):1313–9. doi:10.1038/nature08991.CrossRefPubMed

105.

Woods A, Dickerson K, Heath R, Hong SP, Momcilovic M, Johnstone SR, et al. Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab. 2005;2(1):21–33. doi:10.1016/j.cmet.2005.06.005.CrossRefPubMed

106.

Perez GJ, Bonev AD, Nelson MT. Micromolar Ca(2+) from sparks activates Ca(2+)-sensitive K(+) channels in rat cerebral artery smooth muscle. Am J Physiol Cell Physiol. 2001;281(6):C1769–75.PubMed

107.

Lohn M, Dubrovska G, Lauterbach B, Luft FC, Gollasch M, Sharma AM. Periadventitial fat releases a vascular relaxing factor. FASEB J. 2002;16(9):1057–63. doi:10.1096/fj.02-0024com.CrossRefPubMed

108.

Schleifenbaum J, Kohn C, Voblova N, Dubrovska G, Zavarirskaya O, Gloe T, et al. Systemic peripheral artery relaxation by KCNQ channel openers and hydrogen sulfide. J Hypertens. 2010;28(9):1875–82. doi:10.1097/HJH.0b013e32833c20d5.CrossRefPubMed

109.

Tsvetkov D, Tano JY, Kassmann M, Wang N, Schubert R, Gollasch M. The role of DPO-1 and XE991-sensitive potassium channels in perivascular adipose tissue-mediated regulation of vascular tone. Front Physiol. 2016;7:335. doi:10.3389/fphys.2016.00335.CrossRefPubMedPubMedCentral

110.

Cheng Y, Ndisang JF, Tang G, Cao K, Wang R. Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats. Am J Physiol Heart Circ Physiol. 2004;287(5):H2316–23. doi:10.1152/ajpheart.00331.2004.CrossRefPubMed

111.

Tang G, Wu L, Wang R. Interaction of hydrogen sulfide with ion channels. Clin Exp Pharmacol Physiol. 2010;37(7):753–63. doi:10.1111/j.1440-1681.2010.05351.x.CrossRefPubMed

112.

Kohn C, Schleifenbaum J, Szijarto IA, Marko L, Dubrovska G, Huang Y, et al. Differential effects of cystathionine-gamma-lyase-dependent vasodilatory H2S in periadventitial vasoregulation of rat and mouse aortas. PLoS One. 2012;7(8), e41951. doi:10.1371/journal.pone.0041951.CrossRefPubMedPubMedCentral

113.

Verlohren S, Dubrovska G, Tsang SY, Essin K, Luft FC, Huang Y, et al. Visceral periadventitial adipose tissue regulates arterial tone of mesenteric arteries. Hypertension. 2004;44(3):271–6. doi:10.1161/01.HYP.0000140058.28994.ec.CrossRefPubMed

114.

Gollasch M. KCNQ channels and novel insights into coronary perfusion. Hypertension. 2013;62(6):1011–2. doi:10.1161/HYPERTENSIONAHA.113.01869.CrossRefPubMed

Title: A Clinical Perspective: Contribution of Dysfunctional Perivascular Adipose Tissue (PVAT) to Cardiovascular Risk
Authors: Xiaoming Lian
Maik Gollasch
Publication date: 01-11-2016
Publisher: Springer US
Published in: Current Hypertension Reports / Issue 11/2016
Print ISSN: 1522-6417
Electronic ISSN: 1534-3111
DOI: https://doi.org/10.1007/s11906-016-0692-z

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 11/2016

Isolated Systolic Hypertension in Young and Middle-Aged Adults

Hypertension in Athletes and Active Populations

Pulmonary Arterial Hypertension and the Sex Hormone Paradox

White Coat Hypertension: to Treat or Not to Treat?

Effects of Aspirin on Endothelial Function and Hypertension

Endoluminal Treatments for Obesity and Related Hypertension: Updates, Review, and Clinical Perspective

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials