From skin to heart: a state-of-the-art perspective on psoriasis-driven cardiovascular comorbidities

Psoriasis is a chronic inflammatory disease associated with major adverse cardiovascular events that persist after adjustment for traditional risk factors. The cardiovascular phenotype extends beyond coronary atherosclerosis to involve microvasculature, carotid arteries, and a prothrombotic state. This review integrates preclinical and clinical evidence to delineate the mechanistic relationship between the inflamed skin and the vessel wall. Three converging mechanisms emerge by which skin-derived inflammation reaches the vasculature. The first is a cytokine and matrix-remodeling mechanism. This potentially involves both IL-17A/IL-17F, acting via lysyl oxidase-dependent collagen crosslinking to entrap lipoproteins, and cutaneous IL-6, which serves as a link between skin inflammation and the prothrombotic state of the arterial wall. The second is a T cell-driven mechanism, in which skin-primed effector cells with vascular tropism act on the arterial endothelium and accumulate in atherosclerosis-prone vessels. The third is a myeloid and oxidative mechanism, fueled by inflammatory hematopoiesis and macrophage reprogramming. Across murine models, the cardiovascular phenotype appears more closely linked to the chronicity of inflammation than to the intensity of individual flares. Acute models generally fail to accelerate atherosclerosis, whereas genetic models that sustain chronic inflammation such as the K14-Rac1V12, KC-Tie2 and Card14-mutant models are associated with accelerated atherogenesis. Consistently, in patients, disease duration emerges as an independent predictor of cardiovascular events.