Vasostatins: new molecular targets for atherosclerosis, post-ischaemic angiogenesis, and arteriogenesis

The chromogranin-secretogranin secretory proteins-granins-are acidic proteins localized in granules of endocrine cells and neurons. The chromogranin family includes chromogranins A (CgA) and B, as well as secretogranin II (once called chromogranin C). Members of this family undergo catalytic proteolysis to produce active peptides. The CgA-derived peptides vasostatin-1 and vasostatin-2, in particular, appear to protect against atherosclerosis, suppressing the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, as well as exerting vasodilatory effects by enhancing nitric oxide bioavailability. Vasostatin-1 also suppresses vasoconstriction and abnormal angiogenesis. Vasostatin-1 and vasostatin-2 may be novel therapeutic targets for atherosclerosis and coronary heart disease, also protecting the myocardium against ischaemic damage. Graphical Abstract Vasostatin-1 reduces atherosclerosis and plaque rupture via the reduction of abnormal angiogenesis and plaque hypervascularization. Vasostatin-2 reduces atherosclerosis and promotes angiogenesis and collateral vessel formation via ACE2. ACE2, angiotensin-converting enzyme 2; VCAM-1, vascular cell adhesion molecule-1; ICAM-1, intercellular adhesion molecule-1; IL, interleukin; NO, nitric oxide; eNOS, endothelial nitric oxide synthase; VEGF, vascular endothelial growth factor; OxLDL, oxidized LDL; AngII, angiotensin II; ROS, reactive oxygen species.