J Physiol Biochem. 2026 Oct 3;82(1):100. doi: 10.1007/s13105-026-01237-4.
ABSTRACT
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, yet the molecular mechanisms are incompletely understood. Programmed cell death protein 4 (PDCD4), originally identified as a tumor suppressor and inhibitor of eIF4A-dependent translation, has emerged as a cardiovascular stress-response node. Accumulating evidence indicates that PDCD4 expression is controlled at epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels. Across atherosclerosis, myocardial infarction, myocardial ischemia/reperfusion injury, cardiomyopathy, atrial fibrillation, pulmonary hypertension, and aneurysm, dysregulated PDCD4 links noncoding-RNA signaling and translational control to inflammation, apoptosis, autophagy, oxidative and mitochondrial injury, and phenotypic remodeling. Most experimental studies associate PDCD4 suppression with cardiovascular protection. However, the biological effects of PDCD4 appear to vary according to cell lineage, disease stage, subcellular localization, post-translational state, and tissue microenvironment. This review summarizes the molecular architecture and regulatory networks of PDCD4, integrates disease-specific evidence and cardiovascular functions, and critically discusses the opportunities and challenges of targeting PDCD4 for cardiovascular therapy.
PMID:42828639 | DOI:10.1007/s13105-026-01237-4