Inhibitory effects of vasostatin-1 against atherogenesis
| Autor: | Nozomi Uchiyama, Remina Shirai, Takuya Watanabe, Rena Watanabe, Hatsue Ishibashi-Ueda, Kengo Sato, Tsutomu Hirano, Taka-aki Matsuyama, Yusaku Mori, Yui Takahashi, Nana Ozawa, Yuki Sato |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Mice Knockout ApoE THP-1 Cells CD36 Myocytes Smooth Muscle Apoptosis Inflammation 030204 cardiovascular system & hematology Muscle Smooth Vascular 03 medical and health sciences 0302 clinical medicine Cell Movement Human Umbilical Vein Endothelial Cells medicine Animals Humans Cell adhesion Cell Proliferation Foam cell Extracellular Matrix Proteins Mice Inbred BALB C biology Chemistry Monocyte General Medicine Atherosclerosis Angiotensin II Peptide Fragments Plaque Atherosclerotic Extracellular Matrix Cell biology Fibronectin Endothelial stem cell Disease Models Animal 030104 developmental biology medicine.anatomical_structure biology.protein Chromogranin A Inflammation Mediators medicine.symptom Foam Cells Signal Transduction |
| Zdroj: | Clinical Science. 132:2493-2507 |
| ISSN: | 1470-8736 0143-5221 |
| DOI: | 10.1042/cs20180451 |
| Popis: | Vasostatin-1, a chromogranin A (CgA)-derived peptide (76 amino acids), is known to suppress vasoconstriction and angiogenesis. A recent study has shown that vasostatin-1 suppresses the adhesion of human U937 monocytes to human endothelial cells (HECs) via adhesion molecule down-regulation. The present study evaluated the expression of vasostatin-1 in human atherosclerotic lesions and its effects on inflammatory responses in HECs and human THP-1 monocyte-derived macrophages, macrophage foam cell formation, migration and proliferation of human aortic smooth muscle cells (HASMCs) and extracellular matrix (ECM) production by HASMCs, and atherogenesis in apolipoprotein E-deficient (ApoE−/−) mice. Vasostatin-1 was expressed around Monckeberg’s medial calcific sclerosis in human radial arteries. Vasostatin-1 suppressed lipopolysaccharide (LPS)-induced up-regulation of monocyte chemotactic protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in HECs. Vasostatin-1 suppressed inflammatory M1 phenotype and LPS-induced interleukin-6 (IL-6) secretion via nuclear factor-κB (NF-κB) down-regulation in macrophages. Vasostatin-1 suppressed oxidized low-density lipoprotein (oxLDL)-induced foam cell formation associated with acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) and CD36 down-regulation and ATP-binding cassette transporter A1 (ABCA1) up-regulation in macrophages. In HASMCs, vasostatin-1 suppressed angiotensin II (AngII)-induced migration and collagen-3 and fibronectin expression via decreasing ERK1/2 and p38 phosphorylation, but increased elastin expression and matrix metalloproteinase (MMP)-2 and MMP-9 activities via increasing Akt and JNK phosphorylation. Vasostatin-1 did not affect the proliferation and apoptosis in HASMCs. Four-week infusion of vasostatin-1 suppressed the development of aortic atherosclerotic lesions with reductions in intra-plaque inflammation, macrophage infiltration, and SMC content, and plasma glucose level in ApoE−/− mice. These results indicate the inhibitory effects of vasostatin-1 against atherogenesis. The present study provided the first evidence that vasostatin-1 may serve as a novel therapeutic target for atherosclerosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|