Mind and Motion: A Molecular Convergence Framework of Psychological Stress and Physical Activity in Endothelial Homeostasis

This is the authors' abstract. We don't add key points for this paper.

Objective Psychological stress and physical activity have distinct and often contrasting associations with vascular health, but how these behavioral inputs interact at the molecular level within the endothelium remains largely unexplored. Psychological stress can disrupt endothelial homeostasis through neuroendocrine and hemodynamic pathways that impair nitric oxide (NO) signaling and promote oxidative and inflammatory responses. In contrast, physical activity can generate atheroprotective shear stress that activates endothelial mechanosensing and homeostatic transcriptional programs. This review evaluates the emerging concept that psychological stress and physical activity may converge on shared endothelial signaling networks and examines potential molecular mechanisms through which exercise may modify stress-associated endothelial dysfunction. Methods This is a narrative review of experimental literature. Results Evidence from vascular physiology, endothelial transcriptomics and epigenomics, and mechanistic studies of neuroendocrine and flow-sensitive signaling suggests that stress- and exercise-responsive pathways may intersect through common regulatory nodes. Calcium-dependent mechanotransduction and downstream transcriptional regulation represent candidate points of convergence capable of influencing NO homeostasis, inflammatory signaling, and endothelial phenotypic stability. These shared pathways suggest a molecular framework through which physical activity could counteract or modify endothelial responses to psychological stress. However, although the individual pathways underlying these shared regulatory nodes are supported by experimental evidence, their integration under conditions of combined psychological stress and exercise remains largely unexplored. Conclusions Psychological stress and physical activity may shape endothelial function through interacting rather than independent molecular pathways. Defining how neuroendocrine stress signaling interfaces with flow-sensitive mechanotransduction across vascular beds, exercise modalities, and physiological contexts will be important for establishing when and how physical activity can modify the vascular consequences of chronic psychological stress.