Effect of atorvastatin on TRPC5 expression in atherosclerosis of apolipoprotein E-knockout mice
QI Jie1, XU Fang2, MA Hui1, CUI Jian-guo1, ZHANG Qing-tan1
1. Department of Geriatric Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou 256603, China;
2. Department of Pathophysiology, Binzhou Medical University, Yantai 264003, China
AIM: To observe the changes of transient receptor potential channel 5 (TRPC5) in vascular smooth muscle cells (VSMCs) of apolipoprotein E-knockout (ApoE-/-) mice and the effect of atorvastatin interference, and to investigate the mechanism of atorvastatin therapy. METHODS: Male ApoE-/- mice at 6 weeks of age were used to establish the atherosclerosis model by feeding with hyperlipidic diet. The mice were randomly divided into model group and atorvastatin group. The mice in atorvastatin group were lavaged with atorvastatin at 20 mg·kg-1·d-1, while the mice in model group received normal saline. The healthy C57BL/6J mice with the same age and the same genetic background, feeding with ordinary food, served as control group. At the time points of 14 and 24 weeks, the mice were sacrificed. The serum was collected for detecting the lipid levels. The aortic roots of the heart were taken to make paraffin sections with HE staining for measuring and comparing the relative atherosclerotic plaque area in each section. The expression of TRPC5 in VSMCs was examined with immunohistochemical staining. The mRNA levels of TRPC5 in the serum and the thoracoabdominal aorta were measured by real-time PCR. RESULTS: Compared with model group, blood lipids in atorvastatin group were significantly decreased, and the formation of plaque under aorta intima also decreased. The protein expression of TRPC5 in atorvastatin group decreased significantly compared with model group. Compared with 20-week model group, TRPC5 in 30-week model group showed increasing tendency, but has no statistical significance. Compared with 20-week atorvastatin group, TRPC5 of 30-week atorvastatin group declined. CONCLUSION: Atorvastatin suppresses TRPC5 expression, thus attenuating atherosclerotic development in ApoE-/- mice.
Faxon DP, Fuster V, Libby P, et al. Atherosclerotic Vascular Disease Conference:Writing Group III: pathophysio-logy[J]. Circulation, 2004, 109(21): 2617-2625.
[2]
Touyz RM, Schiffrin EL. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells[J]. Pharmacol Rev, 2000, 52(4):639-672.
Plump AS, Smith JD, Hayek T, et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells[J]. Cell, 1992, 71(2):343-353.
[7]
Zhang SH, Reddick RL, Piedrahita JA, et al. Sponta-neous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E[J]. Science, 1992, 258(5081):468-471.
Massaeli H, Austria JA, Pierce GN. Chronic exposure of smooth muscle cells to minimally oxidized LDL results in depressed inositol 1,4,5-trisphosphate receptor density and Ca2+ transients[J]. Circ Res, 1999, 85(6):515-523.
[10]
Rudijanto A. The role of vascular smooth muscle cells on the pathogenesis of atherosclerosis[J]. Acta Med Indones, 2007, 39(2):86-93.
[11]
Dietrich A, Chubanov V, Kalwa H, et al. Cation channels of the transient receptor potential superfamily: their role in physiological and pathophysiological processes of smooth muscle cells[J]. Pharmacol Ther, 2006, 112(3):744-760.
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines[J]. J Am Coll Cardiol, 2014,63(25):2889-2934.
