Role of perivascular adipose tissue in nicotine‑induced endothelial cell inflammatory responses

Wang,Chao‑Nan; Yang,Gen‑Huan; Wang,Zhan‑Qi; Liu,Chang‑Wei; Li,Tian‑Jia; Lai,Zhi‑Chao; Miao,Shi‑Ying; Wang,Lin‑Fang; Liu,Bao

doi:10.3892/mmr.2016.5934

Role of perivascular adipose tissue in nicotine‑induced endothelial cell inflammatory responses

Authors:
- Chao‑Nan Wang
- Gen‑Huan Yang
- Zhan‑Qi Wang
- Chang‑Wei Liu
- Tian‑Jia Li
- Zhi‑Chao Lai
- Shi‑Ying Miao
- Lin‑Fang Wang
- Bao Liu
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Affiliations: Department of Vascular Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, P.R. China, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, P.R. China
Published online on: November 9, 2016 https://doi.org/10.3892/mmr.2016.5934
Pages: 5713-5718

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Abstract

Smoking is considered to be one of the primary causes of atherosclerosis and vascular injury. Previous studies have shown that nicotine in tobacco can lead to vascular inflammation and endothelial dysfunction. Perivascular adipose tissue (PVAT) is known to secrete various types of adipokines to maintain vascular homeostasis. The present study investigated whether nicotine‑induced PVAT malfunction can accelerate endothelial inflammation and eventually lead to endothelial dysfunction. The levels of inflammatory adipokines, including nuclear factor (NF)‑κB, interleukin (IL)‑1β, IL‑6 and tumor necrosis factor (TNF)‑α, the ICAM‑1 and VCAM‑1 adhesion molecules and secretion of adiponectin were assessed in mature adipocytes and endothelial cells cultured alone or in co‑culture under nicotine stimulation. It was found that nicotine reduced the secretion of adiponectin and stimulated secretion of the NF‑κB, IL‑1β, IL‑6 and TNF‑α inflammatory adipokines in mature adipocytes. Although nicotine stimulated endothelial cells to secrete IL‑1β and IL‑6, no significant increase in the secretion of TNF‑α was observed. The co‑culture of mature adipocytes with endothelial cells markedly augmented the expression of the NF‑κB, IL‑1β, IL‑6 and TNF‑α inflammatory adipokines and the ICAM‑1 and VCAM‑1 adhesion molecules, and significantly lowered the levels of adiponectin. These findings suggested that nicotine induced mature adipocyte dysfunction, which caused the abnormal secretion of adiponectin and inflammatory adipokines, and exacerbated endothelial inflammation. These findings also suggested a mechanism whereby nicotine induced the secretion of adiponectin and inflammatory cytokines by adipocytes. The results of the present study elucidated a novel pathway induced by cigarette smoke, which contributed to atherosclerosis and vascular injury.

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1	Ambrose JA and Barua RS: The pathophysiology of cigarette smoking and cardiovascular disease: An update. J Am Coll Cardiol. 43:1731–1737. 2004. View Article : Google Scholar : PubMed/NCBI
2	Borgerding M and Klus H: Analysis of complex mixtures-cigarette smoke. Exp Toxicol Pathol 57 (Suppl 1). 43–73. 2005. View Article : Google Scholar
3	Lee J, Taneja V and Vassallo R: Cigarette smoking and inflammation: Cellular and molecular mechanisms. J Dent Res. 91:142–149. 2012. View Article : Google Scholar : PubMed/NCBI
4	Orosz Z, Csiszar A, Labinskyy N, Smith K, Kaminski PM, Ferdinandy P, Wolin MS, Rivera A and Ungvari Z: Cigarette smoke-induced proinflammatory alterations in the endothelial phenotype: Role of NAD (P)H oxidase activation. Am J Physiol Heart Circ Physiol. 292:H130–H139. 2007. View Article : Google Scholar : PubMed/NCBI
5	Arnson Y, Shoenfeld Y and Amital H: Effects of tobacco smoke on immunity, inflammation and autoimmunity. J Autoimmun. 34:J258–J265. 2010. View Article : Google Scholar : PubMed/NCBI
6	Kuhlmann CR, Trümper JR, Tillmanns H, Schaefer C Alexander and Erdogan A: Nicotine inhibits large conductance Ca(2+)-activated K(+) channels and the NO/−cGMP signaling pathway in cultured human endothelial cells. Scand Cardiovasc J. 39:348–352. 2005. View Article : Google Scholar : PubMed/NCBI
7	Glantz SA and Parmley WW: Passive and active smoking. A problem for adults. Circulation. 94:596–598. 1996. View Article : Google Scholar : PubMed/NCBI
8	Halberg N, Wernstedt-Asterholm I and Scherer PE: The adipocyte as an endocrine cell. Endocrinol Metab Clin North Am. 37:753–768, x-xi. 2008. View Article : Google Scholar : PubMed/NCBI
9	Lehr S, Hartwig S and Sell H: Adipokines: A treasure trove for the discovery of biomarkers for metabolic disorders. Proteomics Clin Appl. 6:91–101. 2012. View Article : Google Scholar : PubMed/NCBI
10	Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, Arita Y, Okamoto Y, Shimomura I, Hiraoka H, et al: Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 23:85–89. 2003. View Article : Google Scholar : PubMed/NCBI
11	Adamczak M, Wiecek A, Funahashi T, Chudek J, Kokot F and Matsuzawa Y: Decreased plasma adiponectin concentration in patients with essential hypertension. Am J Hypertens. 16:72–75. 2003. View Article : Google Scholar : PubMed/NCBI
12	Ouchi N, Ohishi M, Kihara S, Funahashi T, Nakamura T, Nagaretani H, Kumada M, Ohashi K, Okamoto Y, Nishizawa H, et al: Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension. 42:231–234. 2003. View Article : Google Scholar : PubMed/NCBI
13	Van de Voorde J, Pauwels B, Boydens C and Decaluwé K: Adipocytokines in relation to cardiovascular disease. Metabolism. 62:1513–1521. 2013. View Article : Google Scholar : PubMed/NCBI
14	Suganami T, Tanimoto-Koyama K, Nishida J, Itoh M, Yuan X, Mizuarai S, Kotani H, Yamaoka S, Miyake K, Aoe S, et al: Role of the toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol. 27:84–91. 2007. View Article : Google Scholar : PubMed/NCBI
15	Yamashita A, Soga Y, Iwamoto Y, Yoshizawa S, Iwata H, Kokeguchi S, Takashiba S and Nishimura F: Macrophage-adipocyte interaction: Marked interleukin-6 production by lipopolysaccharide. Obesity (Silver Spring). 15:2549–2552. 2007. View Article : Google Scholar : PubMed/NCBI
16	Lai N, Jayaraman A and Lee K: Enhanced proliferation of human umbilical vein endothelial cells and differentiation of 3T3-L1 adipocytes in coculture. Tissue Eng Part A. 15:1053–1061. 2009. View Article : Google Scholar : PubMed/NCBI
17	Iwashima Y, Katsuya T, Ishikawa K, Kida I, Ohishi M, Horio T, Ouchi N, Ohashi K, Kihara S, Funahashi T, et al: Association of hypoadiponectinemia with smoking habit in men. Hypertension. 45:1094–1100. 2005. View Article : Google Scholar : PubMed/NCBI
18	Gao YJ, Holloway AC, Su LY, Takemori K, Lu C and Lee RM: Effects of fetal and neonatal exposure to nicotine on blood pressure and perivascular adipose tissue function in adult life. Eur J Pharmacol. 590:264–268. 2008. View Article : Google Scholar : PubMed/NCBI
19	Thielen A, Klus H and Müller L: Tobacco smoke: Unraveling a controversial subject. Exp Toxicol Pathol. 60:141–156. 2008. View Article : Google Scholar : PubMed/NCBI
20	Albaugh G, Kann B, Strande L, Vemulapalli P, Hewitt C and Alexander JB: Nicotine induces endothelial TNF-alpha expression, which mediates growth retardation in vitro. J Surg Res. 99:381–384. 2001. View Article : Google Scholar : PubMed/NCBI
21	Deng G, Long Y, Yu YR and Li MR: Adiponectin directly improves endothelial dysfunction in obese rats through the AMPK-eNOS pathway. Int J Obes (Lond). 34:165–171. 2010. View Article : Google Scholar : PubMed/NCBI
22	Wang Y, Wang X, Lau WB, Yuan Y, Booth D, Li JJ, Scalia R, Preston K, Gao E, Koch W and Ma XL: Adiponectin inhibits tumor necrosis factor-alpha-induced vascular inflammatory response via caveolin-mediated ceramidase recruitment and activation. Circ Res. 114:792–805. 2014. View Article : Google Scholar : PubMed/NCBI
23	Wang Y, Wang L, Ai X, Zhao J, Hao X, Lu Y and Qiao Z: Nicotine could augment adhesion molecule expression in human endothelial cells through macrophages secreting TNF-alpha, IL-1beta. Int Immunopharmacol. 4:1675–1686. 2004. View Article : Google Scholar : PubMed/NCBI
24	Ueno H, Pradhan S, Schlessel D, Hirasawa H and Sumpio BE: Nicotine enhances human vascular endothelial cell expression of ICAM-1 and VCAM-1 via protein kinase C, p38 mitogen-activated protein kinase, NF-kappaB, and AP-1. Cardiovasc Toxicol. 6:39–50. 2006. View Article : Google Scholar : PubMed/NCBI
25	Gonçalves RB, Coletta RD, Silvério KG, Benevides L, Casati MZ, da Silva JS and Nociti FH Jr: Impact of smoking on inflammation: Overview of molecular mechanisms. Inflamm Res. 60:409–424. 2011. View Article : Google Scholar : PubMed/NCBI
26	Tsiara S, Elisaf M and Mikhailidis DP: Influence of smoking on predictors of vascular disease. Angiology. 54:507–530. 2003. View Article : Google Scholar : PubMed/NCBI
27	Yanbaeva DG, Dentener MA, Creutzberg EC, Wesseling G and Wouters EF: Systemic effects of smoking. Chest. 131:1557–1566. 2007. View Article : Google Scholar : PubMed/NCBI
28	Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, et al: Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation. 102:1296–1301. 2000. View Article : Google Scholar : PubMed/NCBI
29	Li FY, Cheng KK, Lam KS, Vanhoutte PM and Xu A: Cross-talk between adipose tissue and vasculature: Role of adiponectin. Acta Physiol (Oxf). 203:167–180. 2011. View Article : Google Scholar : PubMed/NCBI