Possible mechanism of neointima formation in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a serious sequel of a number of systemic diseases including cardiopulmonary, inflammatory and autoimmune diseases. Endothelial disruption/dysfunction plays a significant role in the initiation and the progression of the disease. Although modern therapy has improved the quality of life, but the underlying vascular disease progresses unabated; and the survival rate has not improved significantly. The major pathological changes are impaired vascular relaxation response, medial hypertrophy, increased pulmonary pressure; subsequent neointimal formation results in the irreversibility of the disease. Progressive loss of endothelial caveolin-1 (cav-1), a membrane protein has been shown to be associated with reciprocal activation of proliferative pathways and initiation of PAH. Subsequent disruption of endothelial cells and endothelial cav-1 is accompanied by enhanced expression of cav-1 in smooth muscle cells where it becomes proproliferative. This review examines the dual role of cav-1 as a possible contributory mechanism of neointima formation.