Abstract
Catestatin, a catecholamine-release inhibitory peptide, has multiple cardiovascular
activities. Conflicting results have been recently reported by increased or decreased
plasma levels of catestatin in patients with coronary artery disease (CAD). However,
there have been no previous reports regarding the effects of catestatin on arteriosclerosis.
This study evaluated the vasoprotective effects of catestatin on human macrophages,
human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells
(HUVECs) in vitro, and aortic atherosclerosis and wire injury-induced femoral artery
neointimal hyperplasia in apolipoprotein E–deficient (ApoE−/−) mice fed with a high-cholesterol diet. Histological expression of catestatin in
coronary artery lesions and its plasma level were compared between CAD and non-CAD
patients. Catestatin was abundantly expressed in cultured human monocytes, macrophages,
HASMCs and HUVECs. Catestatin significantly suppressed lipopolysaccharide-induced
upregulation of tumour necrosis factor-α, vascular cell adhesion molecule-1 and intercellular
adhesion molecule-1 in HUVECs. Catestatin significantly suppressed inflammatory responses
and oxidized low-density lipoprotein-induced foam cell formation associated with acyl-CoA:cholesterol
acyltransferase-1 downregulation and ATP-binding cassette transporter A1 upregulation
in human macrophages. Catestatin significantly suppressed migration, proliferation
and collagen-1 expression without inducing apoptosis, and increased elastin and fibronectin
expression in HASMCs. Administration of catestatin into ApoE−/− mice significantly retarded entire aortic atherosclerotic lesions with declined contents
of macrophages, SMCs and collagen fibres in atheromatous plaques, but not the femoral
artery injury–induced neointimal hyperplasia. In CAD patients, catestatin levels were
significantly decreased in plasma but increased in coronary atheromatous plaques.
This study provided the first evidence that catestatin could prevent macrophage-driven
atherosclerosis, but not SMC-derived neointimal hyperplasia after vascular injury.
Keywords
catestatin - atherosclerosis - restenosis - macrophage - smooth muscle
