Integrated Stress Response (ISR) Modulators in Vascular Diseases.

ABSTRACT: Vascular dysfunction lies at the core of cardiovascular diseases-the leading cause of global morbidity and mortality. Despite their prevalence, therapeutic options remain limited, in part due to an incomplete understanding of the molecular mechanisms driving vascular pathology. The integrated stress response (ISR), an evolutionarily conserved signaling network activated by diverse stressors, represents a critical but underexplored mechanism in vascular biology. This review examines the dual roles of the core ISR kinases-PERK, GCN2, HRI and PKR-in vascular homeostasis and pathology, including atherosclerosis, pulmonary hypertension, and angiogenesis. We develop a conceptual framework in which the ISR functions as a context-dependent, double-edged sword: while PERK and PKR promote inflammati

SUBMITTER: Kalinin A 

PROVIDER: S-EPMC12786323 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature