《生命科学》 2026, 38(3): 572-586
HSPs在心肌细胞保护中的作用及其研究进展
摘 要：
热休克蛋白（heat shock proteins，HSPs）作为一类关键的分子伴侣蛋白，在维持心肌细胞稳态及应对应激损伤中发挥核心作用。本文系统综述了HSPs通过多重分子机制实现心肌保护的最新研究进展，重点聚焦其激活蛋白质稳态通路、抑制凋亡信号转导、激活抗氧化通路以及调节免疫炎症网络等核心路径。在心肌缺血/再灌注损伤和氧化应激等病理条件下，HSPs通过上述机制增强对心肌细胞的保护效应，为开发相关疾病的创新治疗策略提供理论支持。此外，本文系统梳理了不同运动模式通过调控HSPs的表达发挥心肌保护效应的潜在影响，期望为心血管疾病的非药物干预提供理论依据与转化视角。
通讯作者：黄悦 , Email:huangyue_0616@163.com
Abstract:
This paper aims to systematically review the latest research advances on how heat shock proteins (HSPs) exert cardioprotective effects through multiple molecular mechanisms. It also systematically examines the potential of different exercise modalities to achieve myocardial preservation by regulating HSPs expression. This review provides theoretical support for developing innovative therapeutic strategies for related diseases and offers a theoretical basis and novel translational perspective for non-pharmacological interventions in cardiovascular diseases. As evolutionarily conserved molecular chaperones, HSPs play a central role in physiological and pathological processes, including myocardial ischemia/reperfusion injury (MI/RI) and oxidative stress (OS). They have become a hotspot in cardiovascular disease mechanism research and therapeutic strategy development. In maintaining protein homeostasis, HSPs (such as HSP27, HSP60, HSP70, HSP90) protect cardiomyocytes by facilitating proper folding of nascent polypeptide chains, preventing aggregation of misfolded proteins, activating the ubiquitin-proteasome system, and modulating autophagylysosomal pathways. In regulating myocardial survival and apoptosis, HSPs (such as HSP22, HSP27, HSP70, HSP90) exert crucial protective effects on cardiomyocytes through multiple pathways, including inhibiting apoptosome formation and blocking apoptotic signaling cascades. In promoting injury repair, HSP90 prevents adverse myocardial remodeling by enhancing angiogenesis and regulating cardiac fibroblast activation and collagen metabolism. In response to OS and inflammation, HSPs mitigate damage through multiple mechanisms. They counteract OS by scavenging free radicals, upregulating antioxidant enzyme activity, and activating pathways such as Keap1-Nrf2. Concurrently, HSPs attenuate excessive inflammatory responses during MI/RI by regulating key signaling pathways, including nuclear factor kappa-B (NF-κB) and Toll-like receptor 4 (TLR4). To maintain calcium homeostasis and counteract endoplasmic reticulum (ER) stress under conditions like MI/RI, HSPs (such as HSP27, HSP60, HSP70) act by modulating proteins including sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) and inhibiting the p38-MAPK signaling pathway, thus preventing pathogenic calcium overload. ER-localized HSPs also alleviate excessive ER stress by regulating sensors like R-like ER kinase (PERK) and inositol-requiring enzyme 1α (IRE1α). As key regulators of myocardial protection, HSPs enhance cardioprotective effects through these mechanisms. However, several critical scientific questions remain to be explored in this field. Notably, exercise, as the most potent physiological stressor, holds unique value in regulating HSPs expression and inducing cardio-protection, offering a distinct perspective for nonpharmacological interventions in cardiovascular diseases. Exercise intensity correlates closely with HSPs induction levels. Moderate-intensity aerobic exercise may strike an optimal balance between inducing HSPs expression and achieving myocardial protective benefits. It effectively upregulates HSP70, HSP27 and others, thereby enhancing antioxidant capacity, maintaining protein homeostasis, and promoting autophagy. Different exercise modalities (such as endurance training, interval training) may selectively induce distinct HSP family members, generating myocardial protection through differentiated mechanisms. Although the cardioprotective role of HSPs is well-established, functional redundancy and environmental dependence among family members may render them double-edged swords under specific pathologies. Future research should therefore focus on three areas: first, elucidating the specific functional networks and interactive dialogues of different HSPs within cardiomyocytes; second, elucidating the relationship and mechanisms between exercise-mediated HSPs and myocardial protection; third, exploring novel therapeutic strategies targeting HSPs pathway through exercise or pharmacology. This not only holds promise for identifying new targets in cardiovascular disease prevention and treatment but may also provide a new scientific foundation and intervention strategies for cardiac rehabilitation medicine.
Communication Author：HUANG Yue , Email:huangyue_0616@163.com
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