Proteostasis in cardiac health and disease

Robert H. Henning, Bianca J.J.M. Brundel*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

The incidence and prevalence of cardiac diseases, which are the main cause of death worldwide, are likely to increase because of population ageing. Prevailing theories about the mechanisms of ageing feature the gradual derailment of cellular protein homeostasis (proteostasis) and loss of protein quality control as central factors. In the heart, loss of protein patency, owing to flaws in genetically-determined design or because of environmentally-induced 'wear and tear', can overwhelm protein quality control, thereby triggering derailment of proteostasis and contributing to cardiac ageing. Failure of protein quality control involves impairment of chaperones, ubiquitin-proteosomal systems, autophagy, and loss of sarcomeric and cytoskeletal proteins, all of which relate to induction of cardiomyocyte senescence. Targeting protein quality control to maintain cardiac proteostasis offers a novel therapeutic strategy to promote cardiac health and combat cardiac disease. Currently marketed drugs are available to explore this concept in the clinical setting.

Original languageEnglish
Pages (from-to)637-653
Number of pages17
JournalNature Reviews Cardiology
Volume14
Issue number11
DOIs
Publication statusPublished - 1 Nov 2017

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