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The role of peptide hormones (adiponectin, leptin, insulin) in the pathogenesis of atherosclerosis

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Currently, cardiovascular diseases (CVD) remain the main problem in the world and in Russia in particular. The study of the causes and progression of atherosclerosis is a critical moment in the fight against CVD. Adipose tissue and processes that occur in it attracts attention in recent years. The important role of adipose tissue as an endocrine and immune organ is revealed as well as its participation in the development of the inflammatory process. This leads to the development of initial manifestations of atherosclerosis a precursor of many metabolic disorders and CVD. Particular attention causes adipokines regulatory peptide hormones in the adipose tissue, as well as insulin, due to its close relationship with the adipose tissue and especially with adiponectin and leptin. Recent data on the role of adiponectin, leptin and insulin in the pathogenesis of atherosclerosis in order to identify new potential targets among peptide hormones for the treatment of atherosclerosis are presented. 

About the Authors

S. A. Smetnev
State Research Centre for Preventive Medicine. Petroverigsky per. 10, Moscow, 101990 Russia
Russian Federation

A. N. Meshkov
State Research Centre for Preventive Medicine. Petroverigsky per. 10, Moscow, 101990 Russia
Russian Federation


1. Mathers C.D., Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006;3:e442.

2. Yevseyev ME, Dzhanibekova AR, Eremin MV, et al. Approaches to the assessment of cardiovascular risk in young adults. Profilakticheskaya Meditsina 2011; 5: 7-11. In Russian (Евсеева М. Е., Джанибекова А. Р., Еремин М. В. и др. Подходы к оценке сердечно-сосудистого риска у лиц молодого возраста. Профилактическая Медицина 2011;5:7-11).

3. Konstantinov VV, Deev AD, Balanova YA, et al. The risk profile of cardiovascular health and its contribution to the survival of men and women in Moscow aged 35-64. Profilakticheskaya Meditsina 2013; 1: 3-7. In Russian (Константинов В.В., Деев А.Д., Баланова Ю.А. и др. Профиль риска сердечнососудистого здоровья и его вклад в выживаемость у мужчин и женщин Москвы в возрасте 3564 лет. Профилактическая Медицина 2013;1:3-7).

4. National guidelines on cardiovascular prevention. Kardiovaskulyarnaya Terapiya i Profilaktika 2011; 10 (6) suppl 2: 1-22. In Russian (Национальные рекомендации по кардиоваскулярной профилактике. Кардиоваскулярная Терапия и Профилактика 2011; 10(6) Приложение 2:1-22).

5. Cullen P., Rauterberg J., Lorkowski S. The Pathogenesis of Atherosclerosis. Handb Exp Pharmacol 2005;170:3-70.

6. Matsuura E., Atzeni F., Sarzi-Puttini P., et al. Is Atherosclerosis an autoimmune disease? BMC Med 2014;12:47.

7. Mraz M., Haluzik M. The role of adipose tissue immune cells in obesity and low-grade inflammation. J Endocrinol 2014;222(3):R113-27.

8. Teryaeva NB. Adipokines: regulation of energy metabolism and the pathogenesis of cardiovascular disease. Kreativnaya Kardiologiya 2007; 1-2: 20-5. In Russian (Теряева Н.Б. Адипокины: регуляция энергетического метаболизма и патогенез сердечно-сосудистых заболеваний. Креативная Кардиология 2007;1-2: 20-5).

9. Proença A.R., Sertié R.A., Oliveira A.C., et al. New concepts in white adipose tissue physiology. Braz J Med Biol Res 2014;47(3):192-205.

10. Murdolo G., Smith U. The dysregulated adipose tissue: A connecting link between insulin resistance, type 2 diabetes mellitus and atherosclerosis. Nutrition, Metabolism & Cardiovascular Diseases 2006;16:35-8.

11. Wolk R., Berger P., Lennon R.J., et al. Plasma leptin and prognosis in patients with established coronary atherosclerosis. J Am CollCardiol 2004;44:1819-24.

12. Hao G, Li W., Guo R., et al. Serum total Adiponectin level and the risk of cardiovascular disease in general population: a meta-analysis of 17 prospective studies. Atherosclerosis 2013;228: 29-35.

13. Kumada M., Kihara S., Sumitsuji S., et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 2003;23(1):85-9.

14. Berg A.H., Combs T.P., Scherer P.E. ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 2002;13(2):84-9.

15. Mamaghani F., Zarghami N., Maleki M.J., et al. Variation of Adiponectin Levels in Normal and Obese subjects: Possible Correlation with Lipid Profiles. Int J Endocrinol Metab 2009;3:170-8.

16. Gorshkov IP, Zoloedov VI. Adipokines role in the pathogenesis of type 2 diabetes and metabolic syndrome. Vestnik Novykh Meditsinskikh Tekhnologiy 2010; (1): 132-4. In Russian (Горшков И.П., Золоедов В.И. Роль адипокинов в патогенезе сахарного диабета 2 типа и метаболического синдрома. Вестник Новых Медицинских Технологий 2010;(1):132-4).

17. Vega G.L., Grundy S.M. Metabolic risk susceptibility in men is partially related to adiponectin/leptin ratio. Journal of Obesity 2013;2013: 409679.

18. Bremer A.A., Jialal I. Adipose tissue dysfunction in nascent metabolic syndrome. Journal of Obesity 2013;2013: 393192.

19. Holland W.L., Miller R.A., Wang Z.V., et al. Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat Med 2011;17(1):55-63.

20. Roberts C.R., Sindhu K.K. Oxidative stress and metabolic syndrome. Life Sci 2009;84(21-22):705-12.

21. Nakamura K., Fuster J.J., Walsh K. Adipokines: a link between obesity and cardiovascular disease. J Cardiol 2014;63(4):250-9.

22. Yoon J.H., Kim S.K., Choi H.J., еt al. Adiponectin provides additional information to conventional cardiovascular risk factors for assessing the risk of atherosclerosis in both genders. PLoS One 2013;8(10):e75535.

23. Miyazaki T., Hiki M., Shimada K., et al. The high molecular weight adiponectin level is associated with the atherogenic lipoprotein profiles in healthy Japanese males. J Atheroscler Thromb 2014;21(7): 672-9.

24. Liao H., Li Z., Zheng D., et al. Increased Hs-CRP/adiponectin ratio is associated with increase carotid intima-media thickness. Lipids Health Dis 2014;13:120.

25. Matsuda M., Tamura R., Kishida N., et al. Predictive value of adiponectin in patients with multivessel coronary atherosclerosis detected on computed tomography angiography. J Atheroscler Thromb 2013;20(10):767-76.

26. Kolasa-Trela R., Miszalski-Jamka T., Grudzień G., et al. Adiponectin, leptin, and resistin in patients with aortic stenosis without concomitant atherosclerotic vascular disease. Pol Arch Med Wewn 2011;121(10):352-59.

27. Das K., Lin, Y., Widen E., et al. Chromosomal localization, expression pattern, and promoter analysis of the mouse gene encoding adipocyte-specific secretory protein Acrp30. Biochem Biophys Res Commun 2001;280(4):1120-9.

28. Maeda K., Okubo K., Shimomura I., et al. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (adipose most abundant gene transcript 1). Biochem Biophys Res Commun 1996; 221: 286-9.

29. Schaffler A., Orso E., Palitzsch K.D., et al. The human apM-1, an adipocyte-specific gene linked to the family of TNF's and to genes expressed in activated T cells, is mapped to chromosome 1q21.3-q23, a susceptibility locus identified for familial combined hyperlipidaemia (FCH). Biochem Biophys Res Commun 1999; 260: 416-425.

30. Saito K., Tobe T., Minoshima S., et al. Organization of the gene for gelatin-binding protein (GBP28) Gene1999;229:67-73.

31. Mtiraoui N., Ezzidi I., Turki A., et al. Single-nucleotide polymorphisms and haplotypes in the adiponectin gene contribute to the genetic risk for type 2 diabetes in Tunisian Arabs. Diabetes Res Clin Pract 2012;97(2):290-7.

32. Ramya K., Ayyappa K.A., Ghosh S., et al. Genetic association of ADIPOQ gene variants with type 2 diabetes, obesity and serum adiponectin levels in south Indian population. Gene 2013; 532(2): 253-62.

33. Wassel C.L., Pankow J.S., Rasmussen-Torvik L.J., et al. Associations of SNPs in ADIPOQ and subclinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Obesity (Silver Spring) 2011;19(4):840-7.

34. Zhang F., Chen Y., Heiman M., DiMarchi R. Leptin: Structure, Function and Biology. Vitamins & Hormones 2005;71:345-72.

35. Farooqi I.S., O'Rahilly S. 20 years of leptin: human disorders of leptin action. J Endocrinol 2014;223(1):63-70.

36. Kolaczynski J.W., Nyce M.R., Considine R.V., et al. Acute and chronic effects of insulin on leptin production in humans: Studies in vivo and in vitro. Diabetes 1996;45(5):699-701.

37. Vega G.L., Grundy S.M. Metabolic risk susceptibility in men is partially related to adiponectin/leptin ratio. Journal of Obesity 2013;2013: 409679.

38. Mohamed-Ali V., Pinkney J.H., Panahloo A., et al. Relationships Between Plasma Leptin and Insulin Concentrations, but not Insulin Resistance, in non-insulindependent (Type 2) Diabetes Mellitus. Diabet Med 1997;14(5):376-80.

39. Khafaji H.A., Bener A.B., Rizk N.M., A.I. Suwaidi J. Elevated serum leptin levels in patients with acute myocardial infarction; correlation with coronary angiographic and echocardiographic findings. BMC Res Notes 2012;5:262.

40. Tsiotra P.C., Boutati E., Dimitriadis G., Raptis S.A. High insulin and leptin increase resistin and inflammatory cytokine production from human mononuclear cells. Biomed Res Int 2013;2013:487081.

41. Schneiderman J., Schaefer K., Kolodgie F.D., et al. Leptin locally synthesized in carotid atherosclerotic plaques could be associated with lesion instability and cerebral emboli. J Am Heart Assoc 2012;1(5):e001727.

42. Masuzaki H., Ogawa Y., Isse N., et al. Human obese gene expression: adipocyte-specific expression and regional differences in the adipose tissue. Diabetes 1995;44:855-8.

43. Ogawa Y., Masuzaki H., Isse N., et al. Molecular cloning of rat obese cDNA and augmented gene expression in genetically obese Zucker fatty (fa/fa) rats. J Clin Invest 1995;96:1647-52.

44. Bevan S., Meidtner K., Lorenz M., et al. Adiponectin level as a consequence of genetic variation, but not leptin level or leptin: adiponectin ratio, is a risk factor for carotid intima-media thickness. Stroke 2011;42(6):1510-4.

45. Shen J., Ge W., Zhang J., et al. Leptin -2548g/a Gene Polymorphism in Association with Antipsychotic-Induced Weight Gain: a Meta-Analysis Study. Psychiatr Danub 2014;26(2):145-51.

46. Ng Z.Y., Veerapen M.K., Hon W.M., Lim R.L. Association of leptin/receptor and TNF-α gene variants with adolescent obesity in Malaysia. Pediatr Int 2014;56(5):689-97.

47. Weiss M., Donald F., Steiner M.D., et al. Biosynthesis, Secretion, Structure, and Structure-Activity Relationships. Endotext [Internet] 2000-2009.

48. Sonksen P., Sonksen J. Insulin: understanding its action in health and disease. British Journal of Anaesthesia 2000;85(1):69-79.

49. Girard J. Insulin's effect on the liver: "direct or indirect?" continues to be the question. J Clin Invest 2006;116(2):302-4.

50. Carmena R., Duriez P., Fruchart J. C. Atherogenic lipoprotein particles in atherosclerosis. Circulation 2004;109(23 Suppl 1):III 2-7.

51. Monnier L., Hanefeld M., Schnell O., et al. / Insulin and atherosclerosis: how are they related? Diabetes Metab 2013;39(2):111-7.

52. Huerre C., Gilgenkrantz S., Leonard C., et al. Regional assignment of the structural gene for insulin to 11p15.1-11p15.5 by deletion mapping. (Abstract). Cytogenet Cell Genet 1984;37:495.

53. Steiner D. F., Chan S. J., Welsh J. M., Kwok S. C. M. Structure and evolution of the insulin gene. Annu Rev Genet 1985;19:463-84.

54. Steiner D. F., Oyer P. E. The biosynthesis of insulin and a probable precursor of insulin by a human islet cell adenoma. Proc Nat Acad Sci 1967;57:473-80.

For citation:

Smetnev S.A., Meshkov A.N. The role of peptide hormones (adiponectin, leptin, insulin) in the pathogenesis of atherosclerosis. Rational Pharmacotherapy in Cardiology. 2015;11(5):522-528. (In Russ.)

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