Shoucui Gao1,2, Liran Xu1,2, Yali Zhang1,2, Qingqing Yu1,2, Jiayan Li1, Hua Guan1,2, Xiaojing Wang1,2, Daxin Cheng1,2, Yi Liu1,2, Liang Bai1,2, Rong Wang1,2, Jianglin Fan3, Sihai Zhao4,5,6, Enqi Liu1,2. 1. Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, China. 2. Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, China. 3. Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan. 4. Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Chinasihaizhao@mail.xjtu.edu.cn. 5. Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, Chinasihaizhao@mail.xjtu.edu.cn. 6. Department of Vascular Surgery, Stanford University School of Medicine, Stanford, California, USAsihaizhao@mail.xjtu.edu.cn.
Abstract
BACKGROUND/AIMS: The proliferation and migration of vascular smooth muscle cells (VSMCs) are key steps in the progression of atherosclerosis. The aim of the present study was to investigate the potential roles of salusin-α in the functions of VSMCs during the development of atherosclerosis. METHODS: In vivo, the effects of salusin-α on atherogenesis were examined in rabbits fed a cholesterol diet. The aortas were en face stained with Sudan IV to evaluate the gross atherosclerotic lesion size. The cellular components of atherosclerotic plaques were analyzed by immunohistochemical methods. In vitro, Cell Counting Kit-8 and wound-healing assays were used to assess the effects of salusin-α on VSMC proliferation and migration. In addition, western blotting was used to evaluate the total and phosphorylated levels of Akt (also known as protein kinase B) and mammalian target of rapamycin (mTOR) in VSMCs. RESULTS: Salusin-α infusion significantly reduced the aortic lesion areas of atherosclerosis, with a 39% reduction in the aortic arch, a 71% reduction in the thoracic aorta, and a 71% reduction in the abdominal aorta; plasma lipid levels were unaffected. Immunohistochemical staining showed that salusin-α decreased both macrophage- and VSMC-positively stained areas in atherosclerotic lesions by 54% and 69%, cell proliferative activity in the intima and media of arteriosclerotic lesions, and matrix metalloproteinase 2 (MMP-2) and MMP-9 expression in plaques. Studies using cultured VSMCs showed that salusin-α decreased VSMC migration and proliferation via reduced phosphorylation of Akt and mTOR. CONCLUSION: Our data indicate that salusin-α suppresses the development of atherosclerosis by inhibiting VSMC proliferation and migration through the Akt/mTOR pathway.
BACKGROUND/AIMS: The proliferation and migration of vascular smooth muscle cells (VSMCs) are key steps in the progression of atherosclerosis. The aim of the present study was to investigate the potential roles of salusin-α in the functions of VSMCs during the development of atherosclerosis. METHODS: In vivo, the effects of salusin-α on atherogenesis were examined in rabbits fed a cholesterol diet. The aortas were en face stained with Sudan IV to evaluate the gross atherosclerotic lesion size. The cellular components of atherosclerotic plaques were analyzed by immunohistochemical methods. In vitro, Cell Counting Kit-8 and wound-healing assays were used to assess the effects of salusin-α on VSMC proliferation and migration. In addition, western blotting was used to evaluate the total and phosphorylated levels of Akt (also known as protein kinase B) and mammalian target of rapamycin (mTOR) in VSMCs. RESULTS: Salusin-α infusion significantly reduced the aortic lesion areas of atherosclerosis, with a 39% reduction in the aortic arch, a 71% reduction in the thoracic aorta, and a 71% reduction in the abdominal aorta; plasma lipid levels were unaffected. Immunohistochemical staining showed that salusin-α decreased both macrophage- and VSMC-positively stained areas in atherosclerotic lesions by 54% and 69%, cell proliferative activity in the intima and media of arteriosclerotic lesions, and matrix metalloproteinase 2 (MMP-2) and MMP-9 expression in plaques. Studies using cultured VSMCs showed that salusin-α decreased VSMC migration and proliferation via reduced phosphorylation of Akt and mTOR. CONCLUSION: Our data indicate that salusin-α suppresses the development of atherosclerosis by inhibiting VSMC proliferation and migration through the Akt/mTOR pathway.
Authors: Yuxue Wang; Songjiao Wang; Jun Zhang; Maona Zhang; Hong Zhang; Guofu Gong; Min Luo; Teng Wang; Xiaolu Mao Journal: J Int Med Res Date: 2020-02 Impact factor: 1.671