Oleic acid induces smooth muscle foam cell formation and enhances atherosclerotic lesion development via CD36

Lipids in Health and Disease - 2011
Shuangtao Ma1, Dachun Yang1, De Li1, Bing Tang1, Yongjian Yang1
1Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, 610083, Chengdu, PR, China

Tóm tắt

Abstract Background

Elevated plasma free fatty acid (FFA) levels have been linked to the development of atherosclerosis. However, how FFA causes atherosclerosis has not been determined. Because fatty acid translocase (FAT/CD36) is responsible for the uptake of FFA, we hypothesized that the atherogenic effects of FFA may be mediated via CD36.

 Results

We tested this hypothesis using cultured rat aortic smooth muscle cells (SMCs) treated with oleic acid (OA). We found that OA induces lipid accumulation in SMCs in a dose dependent manner. Rat aortic SMCs treated for 48 hours with OA (250 μmol/L) became foam cells based on morphological (Oil Red O staining) and biochemical (5 times increase in cellular triglyceride) criteria. Moreover, specific inhibition of CD36 by sulfo-N-succinimidyl oleate significantly attenuated OA induced lipid accumulation and foam cell formation. To confirm these results in vivo, we used ApoE-deficient mice fed with normal chow (NC), OA diet, NC plus lipolysis inhibitor acipimox or OA plus acipimox. OA-fed mice showed increased plasma FFA levels and enhanced atherosclerotic lesions in the aortic sinus compared to the NC group (both p < 0.01). This effect was partially reversed by acipimox (lesion area: OA: 3.09 ± 0.10 ×105 μm2 vs. OA plus acipimox: 2.60 ± 0.10 ×105 μm2, p < 0.05; FFA: OA: 0.91 ± 0.03 mmol/L vs. OA plus acipimox: 0.78 ± 0.03 mmol/L, p < 0.05).

 Conclusions

These findings suggest that OA induces smooth muscle foam cell formation and enhances atherosclerotic lesions in part though CD36. Furthermore, these findings provide a novel model for the investigation of atherosclerosis.

Từ khóa


Tài liệu tham khảo

Siegel-Axel D, Daub K, Seizer P, Lindemann S, Gawaz M: Platelet lipoprotein interplay: trigger of foam cell formation and driver of atherosclerosis. Cardiovasc Res. 2008, 78: 8-17. 10.1093/cvr/cvn015

Doran AC, Meller N, McNamara CA: Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arterioscler Thromb Vasc Biol. 2008, 28: 812-819. 10.1161/ATVBAHA.107.159327

Klouche M, Rose-John S, Schmiedt W, Bhakdi S: Enzymatically degraded, nonoxidized LDL induces human vascular smooth muscle cell activation, foam cell transformation, and proliferation. Circulation. 2000, 101: 1799-1805.

Wada Y, Sugiyama A, Yamamoto T, Naito M, Noguchi N, Yokoyama S, Tsujita M, Kawabe Y, Kobayashi M, Izumi A: Lipid accumulation in smooth muscle cells under LDL loading is independent of LDL receptor pathway and enhanced by hypoxic conditions. Arterioscler Thromb Vasc Biol. 2002, 22: 1712-1719. 10.1161/01.ATV.0000033834.57737.9B

Wolfbauer G, Glick JM, Minor LK, Rothblat GH: Development of the smooth muscle foam cell: uptake of macrophage lipid inclusions. Proc Natl Acad Sci USA. 1986, 83: 7760-7764. 10.1073/pnas.83.20.7760

Pomerantz KB, Summers B, Hajjar DP: Eicosanoid metabolism in cholesterol-enriched arterial smooth muscle cells. Evidence for reduced posttranscriptional processing of cyclooxygenase I and reduced cyclooxygenase II gene expression. Biochemistry. 1993, 32: 13624-13635. 10.1021/bi00212a030

Pilz S, Scharnagl H, Tiran B, Seelhorst U, Wellnitz B, Boehm BO, Schaefer JR, Marz W: Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease. J Clin Endocrinol Metab. 2006, 91: 2542-2547. 10.1210/jc.2006-0195

Pirro M, Mauriege P, Tchernof A, Cantin B, Dagenais GR, Despres JP, Lamarche B: Plasma free fatty acid levels and the risk of ischemic heart disease in men: prospective results from the Quebec Cardiovascular Study. Atherosclerosis. 2002, 160: 377-384. 10.1016/S0021-9150(01)00588-3

Smith SR, Wilson PW: Free fatty acids and atherosclerosis--guilty or innocent?. J Clin Endocrinol Metab. 2006, 91: 2506-2508. 10.1210/jc.2006-1018

Hua J, Ma X, Webb T, Potter JJ, Oelke M, Li Z: Dietary fatty acids modulate antigen presentation to hepatic NKT cells in nonalcoholic fatty liver disease. J Lipid Res. 2010, 51: 1696-1703. 10.1194/jlr.M003004

Andersson A, Nalsen C, Tengblad S, Vessby B: Fatty acid composition of skeletal muscle reflects dietary fat composition in humans. Am J Clin Nutr. 2002, 76: 1222-1229.

Collot-Teixeira S, Martin J, McDermott-Roe C, Poston R, McGregor JL: CD36 and macrophages in atherosclerosis. Cardiovasc Res. 2007, 75: 468-477. 10.1016/j.cardiores.2007.03.010

Kwok CF, Juan CC, Ho LT: Endothelin-1 decreases CD36 protein expression in vascular smooth muscle cells. Am J Physiol Endocrinol Metab. 2007, 292: E648-652. 10.1152/ajpendo.00084.2006

Carley AN, Kleinfeld AM: Fatty acid (FFA) transport in cardiomyocytes revealed by imaging unbound FFA is mediated by an FFA pump modulated by the CD36 protein. J Biol Chem. 2011, 286: 4589-4597. 10.1074/jbc.M110.182162

Rong JX, Kusunoki J, Oelkers P, Sturley SL, Fisher EA: Acyl-coenzymeA (CoA):cholesterol acyltransferase inhibition in rat and human aortic smooth muscle cells is nontoxic and retards foam cell formation. Arterioscler Thromb Vasc Biol. 2005, 25: 122-127.

Lim HJ, Lee S, Lee KS, Park JH, Jang Y, Lee EJ, Park HY: PPARgamma activation induces CD36 expression and stimulates foam cell like changes in rVSMCs. Prostaglandins Other Lipid Mediat. 2006, 80: 165-174. 10.1016/j.prostaglandins.2006.06.006

Goldstein JL, Anderson RG, Buja LM, Basu SK, Brown MS: Overloading human aortic smooth muscle cells with low density lipoprotein-cholesteryl esters reproduces features of atherosclerosis in vitro. J Clin Invest. 1977, 59: 1196-1202. 10.1172/JCI108744

Tripathy D, Mohanty P, Dhindsa S, Syed T, Ghanim H, Aljada A, Dandona P: Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. Diabetes. 2003, 52: 2882-2887. 10.2337/diabetes.52.12.2882

Schneider JG, Yang Z, Chakravarthy MV, Lodhi IJ, Wei X, Turk J, Semenkovich CF: Macrophage fatty-acid synthase deficiency decreases diet-induced atherosclerosis. J Biol Chem. 2010, 285: 23398-23409. 10.1074/jbc.M110.100321

Guo W, Wong S, Pudney J, Jasuja R, Hua N, Jiang L, Miller A, Hruz PW, Hamilton JA, Bhasin S: Acipimox, an inhibitor of lipolysis, attenuates atherogenesis in LDLR-null mice treated with HIV protease inhibitor ritonavir. Arterioscler Thromb Vasc Biol. 2009, 29: 2028-2032. 10.1161/ATVBAHA.109.191304

Tang B, Ma ST, Yang YJ, Yang DC, Chen JS, Su XH, Tan Y, Sun MQ, Li D: Overexpression of angiotensin II type 2 receptor suppresses neointimal hyperplasia in a rat carotid arterial balloon injury model. mol Med Rep. 2011, 4: 249-254.

Isenberg JS, Jia Y, Fukuyama J, Switzer CH, Wink DA, Roberts DD: Thrombospondin-1 inhibits nitric oxide signaling via CD36 by inhibiting myristic acid uptake. J Biol Chem. 2007, 282: 15404-15415. 10.1074/jbc.M701638200

Yang D, Ma S, Li D, Tang B, Yang Y: Angiotensin II receptor blockade improves matrix metalloproteinases/tissue inhibitor of matrix metalloproteinase-1 balance and restores fibronectin expression in rat infarcted myocardium. Biochem Biophys Res Commun. 2009, 388: 606-611. 10.1016/j.bbrc.2009.08.073

Yang D, Ma S, Tan Y, Li D, Tang B, Zhang X, Sun M, Yang Y: Increased expression of calpain and elevated activity of calcineurin in the myocardium of patients with congestive heart failure. Int J Mol Med. 2010, 26: 159-164.

Furuhashi M, Tuncman G, Gorgun CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF: Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature. 2007, 447: 959-965. 10.1038/nature05844

Thông tin
Thông tin xuất bản

Lipids in Health and Disease

Thông tin tác giả