The adventitia, vascular inflammation, and the intersection of hypertension and vascular disease.

Hypertension is a leading risk factor for cardiovascular disease, promoting atherosclerosis through interrelated mechanisms of mechanical stress and vascular inflammation. The adventitia and perivascular adipose tissue have emerged as critical sites of immune cell accumulation and cytokine production in hypertension. This review examines the cellular and molecular mechanisms linking adventitial inflammation to vascular stiffening and end-organ damage. Hypertension induces accumulation of effector memory T cells in the adventitia and perivascular fat, driven by chemokines including RANTES/CCL5. Immune cell derived cytokines including IL-17A and IFN-γ promote endothelial dysfunction, vascular superoxide production, and adventitial collagen deposition via p38 MAP kinase activation. Chronic vascular oxidative stress generates isolevuglandin (IsoLG)-protein adducts that act as neoantigens, activating dendritic cells and T cells to drive aortic stiffening that precedes frank hypertension. Stiffened arteries impair Windkessel function and activate microvascular endothelial signaling to adjacent immune cells, further promoting an injurious response in the kidney, brain and vessels. Adventitial and perivascular inflammation are thus not merely consequences of elevated blood pressure but active drivers of vascular disease and end-organ damage through feed-forward immune mechanisms. Targeting these pathways represents a promising therapeutic strategy in hypertension-associated vascular disease.