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目的:本研究旨在揭示高血压条件下血管平滑肌细胞(vascular smooth muscle cells,VSMCs)响应高周期性张应变后调控血管内皮细胞(endothelial cells,ECs)异常增殖的可能机制。方法:在体条件下,构建腹主动脉缩窄型高血压大鼠模型;体外条件下,用FX-4000T张应变加载系统对VSMCs施加5%和15%的周期性张应变。结果:与正常组相比,高血压组大鼠胸主动脉ECs中GRK6的表达水平显著降低,ECs增殖水平显著上升;体内和体外条件均存在VSMCs源性MPs(VSMC-MPs);mi R-27a存在于VSMC-MPs中,并可靶向调控GRK6;15%周期张应变条件下产生的VSMC-MPs中mi R-27a的含量显著高于5%组,作用于ECs后,15%组ECs中mi R-27a的水平显著高于5%组,GRK6的表达水平显著低于5%组,ECs的增殖能力显著高于5%组;用从转染生物素连接的mi R-27a(B-mi R-27a)的VSMCs培养液中分离得到的MPs作用于ECs,在ECs中可以检测到B-mi R-27a的存在;mi R-27a正向调控ECs的增殖,GRK6负向调控ECs的增殖。结论:在高血压条件下,高周期性张应变促进VSMCs分泌mi R-27a,其可通过VSMC-MPs转移到ECs中,抑制GRK6表达,并最终诱导ECs异常增殖。
OBJECTIVE: This study aimed to reveal the possible mechanisms underlying the regulation of abnormal proliferation of vascular endothelial cells (ECs) after vascular smooth muscle cells (VSMCs) under high blood pressure in response to high cyclic tensile strain. Methods: Constructing a rat model of abdominal aortic constriction hypertension under in vivo conditions. In vitro, 5% and 15% of cyclic strain was applied to VSMCs with FX-4000T tensile strain loading system. Results: Compared with the normal group, the expression of GRK6 in the ECs of the thoracic aorta was significantly decreased and the proliferation of ECs was significantly increased in the hypertensive rats. VSMCs-derived MPs (VSMC-MPs) and mi R- 27a was present in VSMC-MPs and targeted to GRK6. The content of mi R-27a in VSMC-MPs produced by 15% cyclic strain was significantly higher than that in 5% group. After ECs treatment, 15% ECs The expression of mi R-27a was significantly higher than that of 5%, the expression of GRK6 was significantly lower than that of 5%, and the proliferation of ECs was significantly higher than that of 5%. Compared with mi R-27a transfected with biotin -mi R-27a) VSMCs culture medium in ECs, the presence of B-mi R-27a can be detected in ECs; mi R-27a positively regulates the proliferation of ECs, negative regulation of GRK6 ECs Proliferation. CONCLUSIONS: In hypertensive conditions, high-cyclic tensile strain stimulates VSMCs to secrete mi R-27a, which translocates to ECs via VSMC-MPs, inhibits GRK6 expression and ultimately induces abnormal proliferation of ECs.