Dysfunctions of vascular smooth muscle cells (VSMCs) play crucial roles in vascular remodeling in hypertension, which correlates with pathologically elevated cyclic stretch due to increased arterial pressure. Recent researches reported that autophagy, a life-sustaining process, was increased in hypertension. However, the mechanobiological mechanism of VSMC autophagy and its potential roles in vascular remodeling are still unclear. Using renal hypertensive rats in vivo and FX5000 stretch application Unit in vitro, the autophagy of VSMCs was detected. The results showed that LC3II remarkably enhanced in hypertensive rats and 15% cyclic stretch (mimic the pathologically increased mechanical stretch in hypertension), and the activity of mammalian target of rapamycin (mTOR) was suppressed in 15% cyclic stretch. Administration of autophagy inhibitors, bafilomycin A1 and chloroquine, repressed VSMC proliferation efficiently, but did not affect the degradation of two important nuclear envelope (NE) proteins, lamin A/C and emerin. Using RNA interference to decline the expression of lamin A/C and emerin, respectively, we discovered that autophagy was upregulated under both static and 5% cyclic stretch conditions, accompanying with the decreased mTOR activity. During 15% cyclic stretch application, mTOR inhibition was responsible for autophagy elevation. Chloroquine administration in vivo inhibited the expression of PCNA (marker of proliferation) of abdominal aorta in hypertensive rats. Altogether, these results demonstrated that pathological cyclic stretch suppresses the expression of lamin A/C and emerin which subsequently represses mTOR pathway so as to induce autophagy activation. Blocking autophagic flux may be a practicable way to relieve the pathological vascular remodeling in hypertensive.

血管平滑肌细胞（VSMC）的功能异常在高血压的血管重塑中起着至关重要的作用，这与由于动脉压升高引起的病理性周期性拉伸相关。最近的研究报道，自噬是一种维持生命的过程，在高血压中增加了。然而，尚不清楚VSMC自噬的力学生物学机制及其在血管重塑中的潜在作用。在体内使用肾性高血压大鼠并在体外使用FX5000拉伸应用装置，检测到VSMC的自噬。结果表明，LC3II在高血压大鼠和15％循环拉伸中显着增强（模仿高血压中病理性机械拉伸的增加），而在15％循环拉伸中雷帕霉素（mTOR）的哺乳动物靶标活性被抑制。自噬抑制剂巴氟霉素A1和氯喹的给药可有效抑制VSMC增殖，但不影响两种重要的核膜蛋白（lamin A / C和emerin）的降解。使用RNA干扰分别降低lamin A / C和emerin的表达，我们发现自噬在静态和5％循环拉伸条件下均被上调，同时mTOR活性降低。在15％的循环拉伸过程中，mTOR抑制是自噬升高的原因。体内抑制高血压大鼠腹主动脉PCNA（增殖标记）的表达。总而言之，这些结果表明病理性循环拉伸抑制层粘连蛋白A / C和emerin的表达，其随后抑制mTOR途径从而诱导自噬激活。阻断自噬通量可能是减轻高血压病理性血管重塑的可行方法。