Cardiovascular diseases (CVDs) have been one of the major causes of human deaths in the world. The study of CVDs has focused on cell chemotaxis for decades. With the advances in mechanobiology, accumulating evidence has demonstrated the influence of mechanical stimuli on arterial pathophysiology and endothelial dysfunction that is a hallmark of atherosclerosis development. An increasing number of drugs have been exploited to decrease the stiffness of vascular tissue for CVDs therapy. However, the underlying mechanisms have yet to be explored. This review aims to summarize how matrix stiffness mediates atherogenesis through various important signaling pathways in endothelial cells and cellular mechanophenotype, including RhoA/Rho-associated protein kinase (ROCK), mitogen-activated protein kinase (MAPK), and Hippo pathways. We also highlight the roles of putative mechanosensitive non-coding RNAs in matrix stiffness-mediated atherogenesis. Finally, we describe the usage of tunable hydrogel and its future strategy to improve our knowledge underlying matrix stiffness-mediated CVDs mechanism.

中文翻译：

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靶向治疗药物在内皮细胞-基质刚度依赖性中的信号传导通路之间的相互作用。

心血管疾病（CVD）是世界上导致人类死亡的主要原因之一。CVD的研究几十年来一直专注于细胞趋化性。随着机械生物学的进步，越来越多的证据表明机械刺激对动脉病理生理和内皮功能障碍的影响，这是动脉粥样硬化发展的标志。已经开发了越来越多的药物来降低用于CVD治疗的血管组织的硬度。但是，尚未探究其基本机制。这篇综述旨在总结基质刚度如何通过内皮细胞和细胞机械表型中的各种重要信号通路介导动脉粥样硬化，包括RhoA / Rho相关蛋白激酶（ROCK），促分裂原活化蛋白激酶（MAPK）和Hippo通路。我们还强调了假定的机械敏感性非编码RNA在基质刚度介导的动脉粥样硬化中的作用。最后，我们描述了可调水凝胶的用途及其未来的策略，以提高我们对基质刚度介导的CVDs机制的认识。