The Role of Adiponectin in Endothelial Dysfunction and Hypertension
- 1.1k Downloads
It has been two decades since the discovery of adiponectin, and today its role in insulin resistance, inflammation, and atherosclerosis are areas of major interest. Production of adiponectin is reduced in all inflammatory processes and states of insulin resistance such as obesity, type 2 diabetes mellitus, and coronary artery disease. Adiponectin regulates carbohydrate metabolism, and may also regulate vascular homeostasis by affecting important signaling pathways in endothelial cells and modulating inflammatory responses in the subendothelial space. Clinical studies have demonstrated a relationship between serum adiponectin concentrations and the activity of the renin-angiotensin-aldosterone system (RAAS), causing changes in blood pressure. Antihypertensive therapy with angiotensin II receptor blockers (ARBs) has been demonstrated to increase adiponectin levels in 3-6 months. Adiponectin has also been shown to play a role in cardiac injury in modulation of pro-survival reactions, cardiac energy metabolism, and inhibition of hypertrophic remodeling. The effects of adiponectin on the cardiovascular system are believed to be partially mediated by the activation of 5’ adenosine monophosphate-activated protein kinase (AMPK) and cyclooxygenase-2 (COX-2) pathways, reducing endothelial cell apoptosis, promoting nitric oxide production, decreasing tumor necrosis factor-alpha (TNF-α) activity, and preventing atherosclerotic proliferation and smooth muscle cell migration. Further evaluation of biologically active forms of adiponectin and its receptor should help to clarify how obesity affects the cardiovascular system.
KeywordsAdiponectin Obesity Hypertension Nitric oxide Renin-angiotensin-aldosterone system Endothelial dysfuction
Compliance with Ethics Guidelines
Conflict of Interest Edward Rojas, Daloha Rodríguez-Molina, Peter Bolli, Zafar H. Israili, Judith Faría, Enzamaría Fidilio, Valmore Bermúdez, and Manuel Velasco each declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 4.American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care. 2014;37(1):S14–80.Google Scholar
- 6.Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant C, American Heart Association, National Heart Lung and Blood Institute. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004;109(3):433–8.PubMedGoogle Scholar
- 7.Alexander CM, Landsman PB, Teutsch SM, Haffner SM, Third National Health and Nutrition Examination Survey NHANES III, National Cholesterol Education Program NCEP. NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes. 2003;52(5):1210–4.PubMedGoogle Scholar
- 9.Alberti KGMM, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–5.PubMedGoogle Scholar
- 13.Elissondo N, Gómez-Rosso L, Maidana P, Brites F. Adiponectin: an adipocytokine with multiple protective functions. Acta Bioquim Clin Latinoam. 2008;42(1):17–33.Google Scholar
- 18.Fumeron F, Aubert R, Siddiq A, et al. Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study. Diabetes. 2004;53(4):1150–7.PubMedGoogle Scholar
- 34.Kharroubi I, Rasschaert J, Eizirik DL, Cnop M. Expression of adiponectin receptors in pancreatic beta cells. Biochem Biophys Res Commun. 2006;312(4):1118–22.Google Scholar
- 36.••Bermúdez VJ, Rojas E, Toledo A, et al. Single-nucleotide polymorphisms in Adiponectin, AdipoR1, and AdipoR2 Genes: insulin resistance and type 2 diabetes mellitus candidate genes. Am J Ther. 2013;20(4):414–21. This review of the literature thoroughly explains the biological and genetic structures of adiponectin and its receptors, particularly in the context of insulin resistance and type 2 diabetes mellitus.PubMedGoogle Scholar
- 40.Bays HE, Abate N, Chandalia M. Adiposopathy: sick fat causes high blood sugar, high blood pressure and dyslipidemia. Futur Cardiol. 2005;1(1):39–59.Google Scholar
- 51.Yilmaz MI, Sonmez A, Caglar K, Celik T, Yenicesu M, Eyileten T, et al. Effect of antihypertensive agents on plasma adiponectin levels in hypertensive patients with metabolic syndrome. Nephrology (Carlton). 2007;12(2):147–53.Google Scholar
- 55.Andrikou I, Tsioufis C, Bafakis I, Kintis K, Almyroudi M, Syrseloudis D, et al. Non‐dipping pattern is related to hypoadiponectinemia and increased arterial stiffness in essential hypertensive subjects. J Hypertens. 2011;29:e447. Monday Posters: Poster Session: Poster Session 31: Blood Pressure Measurement.Google Scholar
- 56.•Baden MY, Yamada Y, Takahi Y, et al. Association of adiponectin with blood pressure in healthy people. Clin Endocrinol (Oxf). 2013;78(2):226–31. This report analyzes the relationship between adiponectin and hypertension in normotensive subjects, demonstrating an inverse association that is present even in the absence of high blood pressure disease.Google Scholar
- 66.Zacharova J, Chiasson J-L, Laakso M, STOP-NIDDM Study Group. The common polymorphisms (single nucleotide polymorphism [SNP] +45 and SNP +276) of the adiponectin gene predict the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial. Diabetes. 2005;54(3):893–9.PubMedGoogle Scholar
- 84.••Funahashi T, Matsuzawa Y. Adiponectin and the cardiometabolic syndrome: an epidemiological perspective. Best Pract Res Clin Endocrinol Metab. 2014;28(1):93–106. This review of the literature structurally reports the relationship between adiponectin and each of the metabolic syndrome components, as well as other diseases such as obstructive sleep apnea-hypopnea syndrome (OSAHS), hepatic steatosis and fibrosis, cancer, and other disorders with paradoxically high levels of adiponectin.PubMedGoogle Scholar