Biophysics and Beyond

Background: In the pathogenesis of ischemic heart disease (IHD), cardiomyocyte apoptosis and endothelial dysfunction act as two parallel processes governed by distinct but interacting mechanisms. In recent years, joint assessment of apoptotic markers such as apoptosis-inducing factor (AIF) and granzyme B, together with endothelial/oxidative stress markers such as nitric oxide (NO), thiol status, cystatin C and endothelin-1, has begun to acquire diagnostic and prognostic relevance. Purpose: This review aims to synthesize the pathophysiological links between the apoptotic pathways of AIF and granzyme B and markers of endothelial dysfunction, based predominantly on literature published over the past five to six years to propose a conceptual framework, termed the Dominance Index (D=A-E, apoptotic minus endothelial), for clinical decision support. Methods: Original studies and review articles published in PubMed and other scientific databases, predominantly between 2020 and 2026, were examined alongside earlier foundational studies where necessary for mechanistic context and pathogenetic and clinical data along the apoptotic-endothelial axes were synthesized. Results: The literature indicates that AIF drives caspase-independent cell death through the mitochondrial-nuclear pathway and is linked to metabolic disease, whereas granzyme B induces endothelial apoptosis both through the cytotoxic T-cell/perforin pathway and through inflammatory-metabolic processes. Cystatin C and endothelin-1 have been confirmed as independent predictors of vascular injury. Conclusion: An integrative index concept reflecting the relative weight of apoptotic and endothelial markers, including the D=A-E model proposed here, represents a promising avenue for personalized risk stratification, though it requires further validation.