Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases

Area of Science:

• Cardiovascular Science
• Cellular Biology
• Molecular Medicine

Background:

• Cardiovascular diseases (CVDs) are a major global health burden, encompassing conditions like heart failure and stroke.
• Many CVDs share underlying mechanisms, including impaired protein homeostasis (proteostasis) within the endoplasmic reticulum (ER).
• The unfolded protein response (UPR) is a cellular pathway that manages ER proteostasis, crucial for cell function.

Purpose of the Study:

• To review the dual role of the UPR and ER stress as both causes and consequences in cardiovascular disease pathogenesis.
• To summarize recent advancements in understanding the UPR and ER stress in CVD.
• To explore therapeutic strategies focused on restoring ER proteostasis for CVD treatment.

Main Methods:

• Literature review of existing research on UPR, ER stress, and CVD.
• Analysis of pathophysiological links between proteostasis disruption and cardiovascular dysfunction.
• Synthesis of current knowledge on therapeutic interventions targeting ER pathways.

Main Results:

• ER stress, characterized by unfolded or misfolded protein accumulation, is a common feature across various CVDs.
• The UPR's adaptive capacity can be overwhelmed, leading to maladaptive responses, ER integrity loss, and apoptosis.
• Chronic ER stress contributes to cellular defects that impair cardiovascular function.

Conclusions:

• The UPR and ER stress play significant roles in the development and progression of cardiovascular diseases.
• Understanding these pathways is critical for developing novel therapeutic approaches.
• Restoring ER proteostasis presents a promising avenue for treating CVDs.