Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases.
Nat Rev Cardiol
; 18(7): 499-521, 2021 07.
Article
en En
| MEDLINE
| ID: mdl-33619348
ABSTRACT
Cardiovascular diseases (CVDs), such as ischaemic heart disease, cardiomyopathy, atherosclerosis, hypertension, stroke and heart failure, are among the leading causes of morbidity and mortality worldwide. Although specific CVDs and the associated cardiometabolic abnormalities have distinct pathophysiological and clinical manifestations, they often share common traits, including disruption of proteostasis resulting in accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER). ER proteostasis is governed by the unfolded protein response (UPR), a signalling pathway that adjusts the protein-folding capacity of the cell to sustain the cell's secretory function. When the adaptive UPR fails to preserve ER homeostasis, a maladaptive or terminal UPR is engaged, leading to the disruption of ER integrity and to apoptosis. ER stress functions as a double-edged sword, with long-term ER stress resulting in cellular defects causing disturbed cardiovascular function. In this Review, we discuss the distinct roles of the UPR and ER stress response as both causes and consequences of CVD. We also summarize the latest advances in our understanding of the importance of the UPR and ER stress in the pathogenesis of CVD and discuss potential therapeutic strategies aimed at restoring ER proteostasis in CVDs.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Cardiovasculares
/
Respuesta de Proteína Desplegada
/
Estrés del Retículo Endoplásmico
Límite:
Humans
Idioma:
En
Revista:
Nat Rev Cardiol
Asunto de la revista:
CARDIOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China