【Animal Modeling】-miR-328 can improve the expression of L-type calcium channels in the thoracic aorta of hypertensive rats by exercise

  Objective To explore the promoting effect of microRNA-328 (miR-328) in improving the expression of volage-gated L-type Ca2+ channel (LTCC) in smooth muscle cells of the thoracic aorta of hypertensive rats by aerobic exercise.

  Methods 12-week-old male normal blood pressure rats (Wistar Kyoto, WKY) and spontaneous hypertensive at (SHR) rats were randomly divided into normal blood pressure control group (WKY-C) and normal blood pressure exercise group (WKY- EX), hypertension control group (SHR-C), hypertension exercise group (SHR-EX), and exercise group for 12 weeks of moderate-intensity treadmill training. Twelve weeks later, femoral arteriovenous catheterization was used to detect the cardiovascular response of the rat; the rat thoracic aorta was taken, and the thoracic aorta morphology was detected by HE staining, and qPCR was used to detect the expression of LTCCα, β, subunit mRNA and miR-328, Western Bloa detects α, and β, subunit protein expression. In vitro experiments, culture WKY thoracic aortic smooth muscle cells, liposome transfection of miR-328mimic and mR-328 ihibior to over-expression or silence them, and detect changes in the expression of LTCCαc and β, subunit mRNA and protein.

  Results (1) Aerobic exercise can significantly reduce SHR body weight, blood pressure and heart rate; (2) Exercise can significantly reduce the thickness of the SHR thoracic aorta; (3) Exercise can significantly reduce SHR's pressure response and nitrate to norepinephrine The antihypertensive response of Nifcdipine (LTCC blocker); (4) The expression of LTCCαn and β, subunit mRNA and protein in SHR-C group was significantly higher than that in WKY-C group, while α, c and SHR-EX group β, subunit mRNA and protein expression was significantly lower than that of SHR-C group; (5) The expression of miR-328 in SHR-C group was significantly lower than that of WKY-C group, and the expression of miR-328 increased significantly after 12 weeks of aerobic exercise (6) In the in vitro experiment, compared with the control group, the α, and β subunit mRNA and protein expressions of the miR-328 mimice transfected group were significantly down-regulated, while the miR-328 inhibitor transfected group α, and β, subunits were significantly down-regulated. The expression of base mRNA and protein was significantly up-regulated.

  Conclusion Regular aerobic exercise can effectively reduce SHR blood pressure, regulate miR-328 to target and inhibit the expression of LTCCα, and β, subunits, which may be one of the mechanisms by which exercise improves LTCC remodeling of the thoracic aorta in hypertension.