Vol. 7, Issue 2, Part D (2025)

Cardiovascular diseases (CVDs) account for nearly 32% of global mortality, with increasing prevalence across all age groups. Atherosclerosis, a key contributor to CVDs, arises from chronic vascular inflammation and is driven by a complex interplay between immune and mechanical factors. Neutrophils play a central role in atherogenesis by releasing reactive oxygen species, proteases, and inflammatory cytokines that damage the endothelium, promote thrombosis, and destabilize plaques. Concurrently, mechanical forces such as wall shear stress (WSS) significantly influence endothelial cell behaviour. Laminar shear stress maintains vascular homeostasis by enhancing nitric oxide synthesis and suppressing inflammatory responses. In contrast, regions exposed to low or oscillatory shear stress exhibit increased expression of adhesion molecules like ICAM-1 and E-selectin, facilitating leukocyte adhesion and transmigration, and contributing to endothelial dysfunction. The mechano-transduction pathways in endothelial cells involve mechano-sensors, signalling intermediates such as MAPKs, and downstream effectors like nitric oxide synthase, collectively determining endothelial responses to hemodynamic forces. Pharmacological suppression of neutrophil recruitment using agents like corticosteroids, mTOR inhibitors, and calcineurin inhibitors has shown potential in mitigating inflammation-driven vascular damage. However, their broad immunosuppressive effects raise concerns regarding infection risk and long-term safety. Integrating the roles of neutrophil-mediated inflammation and shear stress-induced endothelial modulation offers critical insights into the initiation and progression of atherosclerosis, highlighting potential avenues for more targeted and effective therapeutic strategies.