College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
Aurora Bioscience Co., Ltd., Suzhou 215000, China.
Cells. 2022 Oct 31;11(21):3444. doi: 10.3390/cells11213444.
Cardiovascular disease is the result of complicated pathophysiological processes in the tissues that make up the blood vessels and heart. Heat shock protein 90 (HSP90) can interact with 10% of the proteome and is the most widely studied molecular chaperone in recent years. HSP90 is extensively involved in the regulation of protein folding and intracellular protein stability, making HSP90 a hopeful target for the treatment of multiple cardiovascular diseases. Numerous client proteins of HSP90 have been identified in known cardiac disease pathways, including MAPK signaling, PI3K/AKT (PKB)/mTOR, and TNF-α signaling. Therefore, these pathways can be controlled by regulating HSP90. Among them, the activity of HSP90 can be regulated via numerous inhibitors. In this review, first, we will discuss the function of HSP90 and its role in pathological pathways. In addition, HSP90 plays a significant role in most cardiovascular diseases, including hypertension, pulmonary venous hypertension, atherosclerosis, and heart failure; next we will focus on this part. Finally, we will summarize the currently known HSP90 inhibitors and their potential in the treatment of heart disease.
心血管疾病是构成血管和心脏的组织中复杂病理生理过程的结果。热休克蛋白 90（HSP90）可以与 10%的蛋白质组相互作用，是近年来研究最多的分子伴侣。HSP90 广泛参与蛋白质折叠和细胞内蛋白质稳定性的调节，使 HSP90 成为治疗多种心血管疾病的有希望的靶点。在已知的心脏疾病途径中，包括 MAPK 信号、PI3K/AKT（PKB）/mTOR 和 TNF-α 信号，已经鉴定出 HSP90 的许多客户蛋白。因此，可以通过调节 HSP90 来控制这些途径。其中，HSP90 的活性可以通过多种抑制剂来调节。在这篇综述中，我们首先将讨论 HSP90 的功能及其在病理途径中的作用。此外，HSP90 在大多数心血管疾病中都发挥着重要作用，包括高血压、肺静脉高压、动脉粥样硬化和心力衰竭；接下来我们将重点关注这部分。最后，我们将总结目前已知的 HSP90 抑制剂及其在心脏病治疗中的潜力。
