Chemerin and CMKLR1 expression in human arteries and periadventitial fat: a possible role for local chemerin in atherosclerosis?

BMC Cardiovascular Disorders

Helen H Papadaki²  Efstratios Apostolakis¹  John N Varakis²  Sofia G Spiroglou²  Christos G Kostopoulos² 

[1]Department of Cardiac Surgery, University Hospital of Ioannina, School of Medicine, University of Ioannina, 45500 Ioannina, Greece

[2]Department of Anatomy, School of Medicine, University of Patras, 26500 Rio Patras, Greece

关键词: Aorta;    Coronary arteries;    Atherosclerosis;    CMKLR1;    Chemerin;    Periadventitial adipose tissue;   

Others  :  855110
DOI  :  10.1186/1471-2261-14-56

 received in 2013-11-05, accepted in 2014-04-25,  发布年份 2014

【 摘 要 】

Background

Depending on their anatomical location, different fat depots have a different capacity to produce bioactive peptides, called adipokines. Adipokines produced by periadventitial fat have been implicated in the pathogenesis of vascular disease, including atherosclerosis. Chemerin is an adipokine with an established role in immunity, adipose tissue function and metabolism, acting in autocrine, paracrine and endocrine manners. We investigated the protein expression of chemerin and its receptor, CMKLR1, in human aortas, coronary vessels and the respective periadventitial adipose tissue and correlated their expression with the presence of atherosclerosis.

Methods

Immunohistochemistry for chemerin and CMKLR1 was performed on human aortic and coronary artery samples including the periadventitial adipose tissue. Aortic and coronary atherosclerotic lesions were assessed using the AHA classification.

Results

Chemerin immunopositivity was noticed in both periadventitial fat depots, in vascular smooth muscle cells and foam cells in atherosclerotic lesions. Periadventitial fat and foam cell chemerin immunopositivity was statistically significantly correlated with the severity of atherosclerosis in both locations. CMKLR1 was expressed in vascular smooth muscle cells and foam cells in aortic and coronary vessels with atherosclerotic lesions. CMKLR1 immunostaining in foam cells was statistically significantly correlated with aortic atherosclerosis.

Conclusions

Our results lend some support to a presumable role of locally produced chemerin in the progression of atherosclerotic lesions, possibly acting through its CMKLR1 receptor. Further research will elucidate the role of chemerin signaling in atherosclerosis.

【 授权许可】

   
2014 Kostopoulos et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Ronti T, Lupattelli G, Mannarino E: The endocrine function of adipose tissue: an update. Clin Endocrinol (Oxf) 2006, 64(4):355-365.
• [2]Gustafson B: Adipose tissue, inflammation and atherosclerosis. J Atheroscler Thromb 2010, 17(4):332-341.
• [3]Chaldakov GN, Beltowsky J, Ghenev PI, Fiore M, Panayotov P, Rančič G, Aloe L: Adipoparacrinology – vascular periadventitial adipose tissue (tunica adiposa) as an example. Cell Biol Int 2012, 36(3):327-330.
• [4]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):2223-2234.
• [5]Verhagen SN, Visseren FL: Perivascular adipose tissue as a cause of atherosclerosis. Atherosclerosis 2011, 214(1):3-10.
• [6]Yamawaki H: Vascular effects of novel adipocytokines: focus on vascular contractility and inflammatory responses. Biol Pharm Bull 2011, 34(3):307-310.
• [7]Yudkin JS, Eringa E, Stehouwer CD: "Vasocrine" signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet 2005, 365(9473):1817-1820.
• [8]Iacobellis G, Bianco AC: Epicardial adipose tissue: emerging physiological, pathophysiological and clinical features. Trends Endocrinol Metab 2011, 22(11):450-457.
• [9]Szasz T, Webb RC: Perivascular adipose tissue: more than just structural support. Clin Sci (Lond) 2012, 122(1):1-12.
• [10]Xu A, Wang Y, Lam KS, Vanhoutte PM: Vascular actions of adipokines molecular mechanisms and therapeutic implications. Adv Pharmacol 2010, 60:229-255.
• [11]Wittamer V, Franssen JD, Vulcano M, Mirjolet JF, Le Poul E, Migeotte I, Brézillon S, Tyldesley R, Blanpain C, Detheux M, Mantovani A, Sozzani S, Vassart G, Parmentier M, Communi D: Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J Exp Med 2003, 198(7):977-985.
• [12]Goralski KB, McCarthy TC, Hanniman EA, Zabel BA, Butcher EC, Parlee SD, Muruganandan S, Sinal CJ: Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem 2007, 282(38):28175-28188.
• [13]Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, Walder K, Segal D: Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 2007, 148(10):4687-4694.
• [14]Bondue B, Wittamer V, Parmentier M: Chemerin and its receptors in leukocyte trafficking, inflammation and metabolism. Cytokine Growth Factor Rev 2011, 22(5–6):331-338.
• [15]Dong B, Ji W, Zhang Y: Elevated serum chemerin levels are associated with the presence of coronary artery disease in patients with metabolic syndrome. Intern Med 2011, 50(10):1093-1097.
• [16]Gao X, Mi S, Zhang F, Gong F, Lai Y, Gao F, Zhang X, Wang L, Tao H: Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis. Cardiovasc Diabetol 2011, 10:87. BioMed Central Full Text
• [17]Landgraf K, Friebe D, Ullrich T, Kratzsch J, Dittrich K, Herberth G, Adams V, Kiess W, Erbs S, Körner A: Chemerin as a mediator between obesity and vascular inflammation in children. J Clin Endocrinol Metab 2012, 97(4):E556-E564.
• [18]Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM: Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000, 20(5):1262-1275.
• [19]Spiroglou SG, Kostopoulos CG, Varakis JN, Papadaki HH: Adipokines in periaortic and epicardial adipose tissue: differential expression and relation to atherosclerosis. J Atheroscler Thromb 2010, 17(2):115-130.
• [20]Jialal I, Devaraj S, Kaur H, Adams-Huet B, Bremer AA: Increased Chemerin and Decreased Omentin-1 in Both Adipose Tissue and Plasma in Nascent Metabolic Syndrome. J Clin Endocrinol Metab 2013, 98(3):E514-E517.
• [21]Hart R, Greaves DR: Chemerin contributes to inflammation by promoting macrophage adhesion to VCAM-1 and fibronectin through clustering of VLA-4 and VLA-5. J Immunol 2010, 185(6):3728-3739.
• [22]Ho KJ, Spite M, Owens CD, Lancero H, Kroemer AH, Pande R, Creager MA, Serhan CN, Conte MS: Aspirin-triggered lipoxin and resolvin E1 modulate vascular smooth muscle phenotype and correlate with peripheral atherosclerosis. Am J Pathol 2010, 177(4):2116-2123.
• [23]Kaur J, Adya R, Tan BK, Chen J, Randeva HS: Identification of chemerin receptor (ChemR23) in human endothelial cells: chemerin-induced endothelial angiogenesis. Biochem Biophys Res Commun 2010, 391(4):1762-1768.
• [24]Arita M, Ohira T, Sun YP, Elangovan S, Chiang N, Serhan CN: Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J Immunol 2007, 178(6):3912-3917.
• [25]Bondue B, De Henau O, Luangsay S, Devosse T, de Nadaï P, Springael JY, Parmentier M, Vosters O: The chemerin/ChemR23 system does not affect the pro-inflammatory response of mouse and human macrophages ex vivo. PLoS One 2012, 7(6):e40043.
• [26]Zhao RJ, Wang H: Chemerin/ChemR23 signaling axis is involved in the endothelial protection by K(ATP) channel opener iptakalim. Acta Pharmacol Sin 2011, 32(5):573-580.
• [27]Monnier J, Lewén S, O'Hara E, Huang K, Tu H, Butcher EC, Zabel BA: Expression, regulation, and function of atypical chemerin receptor CCRL2 on endothelial cells. J Immunol 2012, 189(2):956-967.
• [28]Xiaotao L, Xiaoxia Z, Yue X, Liye W: Serum chemerin levels are associated with the presence and extent of coronary artery disease. Coron Artery Dis 2012, 23(6):412-416.
• [29]Yoo HJ, Choi HY, Yang SJ, Kim HY, Seo JA, Kim SG, Kim NH, Choi KM, Choi DS, Baik SH: Circulating chemerin level is independently correlated with arterial stiffness. J Atheroscler Thromb 2012, 19(1):59-68.
• [30]Lehrke M, Becker A, Greif M, Stark R, Laubender RP, von Ziegler F, Lebherz C, Tittus J, Reiser M, Becker C, Göke B, Leber AW, Parhofer KG, Broedl UC: Chemerin is associated with markers of inflammation and components of the metabolic syndrome but does not predict coronary atherosclerosis. Eur J Endocrinol 2009, 161(2):339-344.
• [31]Neves KB, Lobato NS, Lopes RA, Filgueira FP, Zanotto CZ, Oliveira AM, Tostes RC: Chemerin reduces vascular nitric oxide ‒ cyclic guanosine monophosphate signaling: a link to vascular dysfunction in obesity? Clin Sci (Lond) 2014, 127(2):111-122.