Department of Clinical Pharmacy and Pharmacology, EB71, University Institute for Drug Exploration (GUIDE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Clinical Pharmacy and Pharmacology, EB71, University Institute for Drug Exploration (GUIDE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Trends Cardiovasc Med. 2015 Apr;25(3):243-7. doi: 10.1016/j.tcm.2014.10.013. Epub 2014 Oct 28.
It has been firmly established that ageing constitutes a principal risk factor for cardiac disease. Currently, the underlying mechanisms of ageing that contribute to the initiation or acceleration of cardiac disease are essentially unresolved. Prevailing theories of ageing center on the loss of cellular protein homeostasis, by either design (genetically) or "wear and tear" (environmentally). Either or both ways, the normal protein homeostasis in the cell is affected, resulting in aberrant and misfolded proteins. Should such misfolded proteins escape the protein quality control (PQC) system, they become proteotoxic and accelerate the loss of cellular integrity. Impairment of PQC plays a prominent role in the pathophysiology of ageing-related neurodegenerative disorders such as Parkinson's, Huntington׳s, and Alzheimer׳s disease. The concept of an impaired PQC driving ageing-related diseases has recently been expanded to cardiac diseases, including atrial fibrillation, cardiac hypertrophy, and cardiomyopathy. In this review, we provide a brief overview of the PQC system in relation to ageing and discuss the emerging concept of the loss of PQC in cardiomyocytes as a trigger for cardiac disease. Finally, we discuss the potential of boosting the PQC system as an innovative therapeutic target to treat cardiac disease in the elderly.
衰老是导致心脏病的主要危险因素，这一点已得到明确证实。目前，导致心脏病发生或加速的与衰老相关的潜在机制尚未完全阐明。目前的衰老理论主要集中在细胞蛋白质内稳态的丧失上，其原因可能是遗传设计（基因）或“磨损”（环境）。无论哪种方式，细胞的正常蛋白质内稳态都会受到影响，导致异常和错误折叠的蛋白质。如果这些错误折叠的蛋白质逃脱了蛋白质质量控制系统（PQC），它们就会变得有毒，并加速细胞完整性的丧失。PQC 的损害在与衰老相关的神经退行性疾病（如帕金森病、亨廷顿病和阿尔茨海默病）的病理生理学中起着重要作用。最近，PQC 受损导致与衰老相关疾病的概念已扩展到心脏病，包括心房颤动、心脏肥大和心肌病。在这篇综述中，我们简要概述了 PQC 系统与衰老的关系，并讨论了 PQC 在心肌细胞中丧失作为心脏病诱因的新兴概念。最后，我们讨论了增强 PQC 系统作为治疗老年人心血管疾病的创新治疗靶点的潜力。
