Reframing Skeletal Muscle Angiogenesis: A Determinant, Not a Consequence, of Hypertrophic Adaptation to Resistance Training

Abstract

Introduction: Exercise-induced skeletal muscle angiogenesis is governed by regulators such as vascular endothelial growth factor (VEGF) and thrombospondin 1 (TSP-1) and is classically attributed to aerobic training. While aerobic exercise is well established as a key driver of capillary adaptation, the purpose of capillary expansion during resistance training remains unclear. This review evaluates angiogenic regulation and evaluates whether vascular remodeling functions as a permissive, active contributor to muscle hypertrophy.

Methods: Literature was identified through PubMed, Scopus, and Google Scholar using terms related to skeletal muscle angiogenesis, resistance exercise, VEGF, and TSP-1with studies from 2015 onward prioritized alongside key seminal papers. As a narrative review, studies were selected for relevance to the research objectives rather than predefined inclusion criteria, allowing a comprehensive synthesis of mechanisms underlying vascular adaptation.

Results: Endurance exercise stimulates angiogenesis through mechanical and metabolic signals, with myofiber-derived VEGF acting as the essential driver of endothelial activation and capillary growth. This response is shaped by fiber-type hypoxia, endothelial metabolism, and the VEGF and TSP-1 balance. Resistance exercise also engages VEGF-dependent pathways, and myofiber-specific VEGF deletion demonstrates that preserving the capillary network is necessary for full hypertrophic adaptation. Angiogenesis can precede or scale with muscle growth, and baseline capillarization strongly predicts hypertrophic potential, indicating that vascular remodeling functions as a permissive mechanism supporting adaptation.

Discussion: Detraining rapidly shifts muscle toward an anti-angiogenic state, with early suppression of VEGF and increases in TSP-1 preceding controlled, partially reversible capillary rarefaction. Aging further limits angiogenic potential by reducing baseline capillarization and blunting VEGF responsiveness, producing a vasculature that is less plastic and less capable of supporting hypertrophic adaptation. Metabolic conditions such as obesity also disrupt this balance, as elevated TSP-1 creates an inhibitory endothelial environment even when VEGF expression is preserved.

Conclusion: Overall, the literature shows that skeletal muscle capillarization is essential for functional adaptation, that VEGF and TSP-1 signalling governs exercise-induced angiogenesis, and that vascular expansion acts as a permissive driver of hypertrophy, a relationship that persists across detraining, aging, and obesity.