Cathepsin G activity lowers plasma LDL and reduces atherosclerosis

AbstractCathepsin G (CatG), a serine protease present in mast cells and neutrophils, can produce angiotensin-II (Ang-II) and degrade elastin. Here we demonstrate increased CatG expression in smooth muscle cells (SMCs), endothelial cells (ECs), macrophages, and T cells from human atherosclerotic lesions. In low-density lipoprotein (LDL) receptor-deficient (Ldlr–/–) mice, the absence of CatG reduces arterial wall elastin degradation and attenuates early atherosclerosis when mice consume a Western diet for 3months. When mice consume this diet for 6months, however, CatG deficiency exacerbates atherosclerosis in aortic arch without affecting lesion inflammatory cell content or extracellular matrix accumulation, but raises plasma total cholesterol and LDL levels without affecting high-density lipoprotein (HDL) or triglyceride levels. Patients with atherosclerosis also have significantly reduced plasma CatG levels that correlate inversely with total cholesterol (r=–0.535, P<0.0001) and LDL cholesterol (r=–0.559, P<0.0001), but not with HDL cholesterol (P=0.901) or triglycerides (P=0.186). Such inverse correlations with total cholesterol (r=–0.504, P<0.0001) and LDL cholesterol (r=–0.502, P