Vol 15, No 4 (2019):179-184

Immunohistochemical analysis of adiponectin in atherosclerotic lesions of human aorta

Dmitry A Tanyanskiy, Peter V Pigarevskii, Svetlana V Maltseva, Alexander D Denisenko



DOI: http://dx.doi.org/10.22122/arya.v15i4.1873

Abstract


BACKGROUND: Metabolic syndrome, a cluster of interrelated disorders including abdominal obesity, insulin resistance, dyslipidemia, and hypertension (HTN) plays an important role in development of atherosclerotic lesions in arterial wall. Dysregulation of adipose tissue hormones (adipokines) production is a possible link between abdominal obesity and other manifestations of metabolic syndrome. Adiponectin is a well-known adipokine which affects metabolism and inflammatory response. However, data on its role in atherogenesis are still controversial. The aim of this study is to investigate whether adiponectin is present in atherosclerotic lesions of human aorta.

METHODS: Thirty-five autopsy segments from abdominal, thoracic aortas, and aortic arch of four men (mean age: 57 years) were fixed and stained for lipids [Oil Red O (ORO)], cells [hematoxylin-eosin (H&E)], and adiponectin [indirect immunoperoxidase assay (IPA) method]. Samples of both stable and unstable plaques were selected for analysis. Human adipose tissue, THP-1 monocytes/macrophages, and human endothelial hybrid cell line (EA.hy926) were chosen for detection of adiponectin messenger ribonucleic acid (mRNA) using reverse transcription polymerase chain reaction (RT-PCR).

RESULTS: Adiponectin accumulations were found inside endothelial cells covering both stable and unstable atherosclerotic plaques. Focal depositions of adiponectin were also found in fibrous caps of stable lesions and atheromatous core of both stable and unstable plaques and also in adventitia. RT-PCR revealed mRNA expression of adiponectin gene in adipose tissue, but not in mononuclears and endothelial cells.

CONCLUSION: Adiponectin is present in aortic plaques of humans, but is not synthesized in endothelial cells and mononuclears, at least in culture conditions. Detection of adiponectin in atherosclerotic lesions can serve as indirect evidence of possible participation of this adipokine in atherogenesis.

 


Keywords


Adiponectin; Atherosclerosis; Aorta; Endothelium

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References


Tabas I, Garcia-Cardena G, Owens GK. Recent insights into the cellular biology of atherosclerosis. J Cell Biol 2015; 209(1): 13-22.

Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, 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.

Kwasny C, Manuwald U, Kugler J, Rothe U. Systematic review of the epidemiology and natural history of the metabolic vascular syndrome and its coincidence with type 2 diabetes mellitus and cardiovascular diseases in different European countries. Horm Metab Res 2018; 50(3): 201-8.

Freitas Lima LC, Braga VA, do Socorro de Franca Silva, Cruz JC, Sousa Santos SH, de Oliveira Monteiro MM, et al. Adipokines, diabetes and atherosclerosis: An inflammatory association. Front Physiol 2015; 6: 304.

Kishida K, Funahashi T, Shimomura I. Molecular mechanisms of diabetes and atherosclerosis: Role of adiponectin. Endocr Metab Immune Disord Drug Targets 2012; 12(2): 118-31.

Lee YA, Ji HI, Lee SH, Hong SJ, Yang HI, Chul YM, et al. The role of adiponectin in the production of IL-6, IL-8, VEGF and MMPs in human endothelial cells and osteoblasts: Implications for arthritic joints. Exp Mol Med 2014; 46: e72.

Folco EJ, Rocha VZ, Lopez-Ilasaca M, Libby P. Adiponectin inhibits pro-inflammatory signaling in human macrophages independent of interleukin-10. J Biol Chem 2009; 284(38): 25569-75.

Wang M, Wang D, Zhang Y, Wang X, Liu Y, Xia M. Adiponectin increases macrophages cholesterol efflux and suppresses foam cell formation in patients with type 2 diabetes mellitus. Atherosclerosis 2013; 229(1): 62-70.

Wang Y, Wang X, Lau WB, Yuan Y, Booth D, Li JJ, et al. Adiponectin inhibits tumor necrosis factor-alpha-induced vascular inflammatory response via caveolin-mediated ceramidase recruitment and activation. Circ Res 2014; 114(5): 792-805.

Du Y, Li R, Lau WB, Zhao J, Lopez B, Christopher TA, et al. Adiponectin at physiologically relevant concentrations enhances the vasorelaxative effect of acetylcholine via Cav-1/AdipoR-1 signaling. PLoS One 2016; 11(3): e0152247.

Tian L, Luo N, Klein RL, Chung BH, Garvey WT, Fu Y. Adiponectin reduces lipid accumulation in macrophage foam cells. Atherosclerosis 2009; 202(1): 152-61.

Motobayashi Y, Izawa-Ishizawa Y, Ishizawa K, Orino S, Yamaguchi K, Kawazoe K, et al. Adiponectin inhibits insulin-like growth factor-1-induced cell migration by the suppression of extracellular signal-regulated kinase 1/2 activation, but not Akt in vascular smooth muscle cells. Hypertens Res 2009; 32(3): 188-93.

Zhang W, Shu C, Li Q, Li M, Li X. Adiponectin affects vascular smooth muscle cell proliferation and apoptosis through modulation of the mitofusin-2-mediated Ras-Raf-Erk1/2 signaling pathway. Mol Med Rep 2015; 12(3): 4703-7.

Parker-Duffen JL, Nakamura K, Silver M, Kikuchi R, Tigges U, Yoshida S, et al. T-cadherin is essential for adiponectin-mediated revascularization. J Biol Chem 2013; 288(34): 24886-97.

Kostopoulos CG, Spiroglou SG, Varakis JN, Apostolakis E, Papadaki HH. Adiponectin/T-cadherin and apelin/APJ expression in human arteries and periadventitial fat: Implication of local adipokine signaling in atherosclerosis? Cardiovasc Pathol 2014; 23(3): 131-8.

Fujishima Y, Maeda N, Matsuda K, Masuda S, Mori T, Fukuda S, et al. Adiponectin association with T-cadherin protects against neointima proliferation and atherosclerosis. FASEB J 2017; 31(4): 1571-83.

Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem 2003; 278(4): 2461-8.

Nawrocki AR, Hofmann SM, Teupser D, Basford JE, Durand JL, Jelicks LA, et al. Lack of association between adiponectin levels and atherosclerosis in mice. Arterioscler Thromb Vasc Biol 2010; 30(6): 1159-65.

Wang Y, Zheng A, Yan Y, Song F, Kong Q, Qin S, et al. Association between HMW adiponectin, HMW-total adiponectin ratio and early-onset coronary artery disease in Chinese population. Atherosclerosis 2014; 235(2): 392-7.

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.

Mori T, Koyama Y, Maeda N, Nakamura Y, Fujishima Y, Matsuda K, et al. Ultrastructural localization of

adiponectin protein in vasculature of normal and atherosclerotic mice. Sci Rep 2014; 4: 4895.

Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R. Update on acute coronary syndromes: The pathologists' view. Eur Heart J 2013; 34(10): 719-28.

Mogilenko DA, Orlov SV, Trulioff AS, Ivanov AV, Nagumanov VK, Kudriavtsev IV, et al. Endogenous apolipoprotein A-I stabilizes ATP-binding cassette transporter A1 and modulates Toll-like receptor 4 signaling in human macrophages. FASEB J 2012; 26(5): 2019-30.

Starikova EA, Sokolov AV, Vlasenko AY, Burova LA, Freidlin IS, Vasilyev VB. Biochemical and biological activity of arginine deiminase from Streptococcus pyogenes M22. Biochem Cell Biol 2016; 94(2): 129-37.

Kim SJ, Kim JS, Papadopoulos J, Wook Kim S, Maya M, Zhang F, et al. Circulating monocytes expressing CD31: Implications for acute and chronic angiogenesis. Am J Pathol 2009; 174(5): 1972-80.

Shavva VS, Bogomolova AM, Nikitin AA, Dizhe EB, Tanyanskiy DA, Efremov AM, et al. Insulin-mediated downregulation of apolipoprotein A-I gene in human hepatoma cell line HepG2: The role of interaction between FOXO1 and LXRbeta transcription factors. J Cell Biochem 2017; 118(2): 382-96.

Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001; 103(8): 1057-63.

Gasbarrino K, Zheng H, Hafiane A, Veinot JP, Lai C, Daskalopoulou SS. Decreased adiponectin-mediated signaling through the adipor2 pathway is associated with carotid plaque instability. Stroke 2017; 48(4): 915-24.

Ding M, Carrao AC, Wagner RJ, Xie Y, Jin Y, Rzucidlo EM, et al. Vascular smooth muscle cell-derived adiponectin: A paracrine regulator of contractile phenotype. J Mol Cell Cardiol 2012; 52(2): 474-84.

Komura N, Maeda N, Mori T, Kihara S, Nakatsuji H, Hirata A, et al. Adiponectin protein exists in aortic endothelial cells. PLoS One 2013; 8(8): e71271.


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