The SIK Axis and Cardiovascular Disease: Selenium-Dependent Selenoproteins, CoQ10-FSP1 Anti-Ferroptotic Defense, and T3-Mediated Coronary Vasodilation as Three Convergent Determinants of Cardiac Mitochondrial Protection

This paper proposes that cardiac mitochondria are governed by the Selenoprotein Axis framework through three specific selenoprotein-dependent mechanisms: (1) TrxR2, the mitochondria-specific thioredoxin reductase selenoenzyme, provides primary redox defense in the cardiac inner mitochondrial membrane; (2) GPx4 suppresses ferroptosis in cardiomyocytes, documented in ischemia-reperfusion injury, doxorubicin cardiotoxicity, and heart failure; (3) T3-mediated coronary artery vasodilation maintains perfusion pressure through selenium-dependent deiodinase T4-to-T3 conversion. The KiSel-10 randomized controlled trial demonstrated 40% reduction in cardiovascular mortality over 12 years from selenium yeast 200mcg plus CoQ10 200mg daily in selenium-insufficient elderly populations. Keshan disease provides historical proof of concept. All claims are hypothesis-level requiring prospective clinical confirmation.