Background: Caveolin-1 (Cav-1) is a protein found in various forms and locations within cells and tissues throughout the body. Studying its structure and function provides valuable insights into key cellular processes such as growth, death, and cell signaling. This review synthesizes evidence from human studies and animal models to elucidate the complex role of Caveolin-1 (Cav-1) in regulating nitric oxide (NO) synthesis within the vasculature and perivascular adipose tissue (PVAT) during atherosclerosis. Cav-1 is a master regulator of endothelial NO synthase (eNOS), a relationship well-defined in rodent endothelial cells and cell lines. In humans, loss-of-function CAV1 mutations are linked to pulmonary arterial hypertension, suggesting a protective vascular role. Paradoxically, Cav-1 is upregulated in atherosclerotic plaques. Whether this represents a pathological process reducing NO bioavailability or a compensatory response remains unclear. Furthermore, the direct translation of the Cav-1/eNOS axis to PVAT—a metabolically active tissue expressing Cav-1—is not fully established outside of preclinical models. PVAT influences vascular tone and inflammation, potentially contributing to the paradoxical, stage-specific roles of Cav-1 in disease. Resolving these questions requires integrating human observational data with mechanistic insights from animal models to evaluate Cav-1 as a therapeutic target in vascular disease.
Hwej et al. (Thu,) studied this question.