title: Class A scavenger receptor deficiency augments angiotensin II-induced vascular remodeling.
abstract: Class A scavenger receptor (SR-A) is a multifunctional molecule that participates in macrophage-mediated inflammation. Here we evaluated the role of SR-A in angiotensin II (Ang II)-induced hypertensive vascular remodeling. Chronic infusion of Ang II leads to an increased systolic blood pressure both in SR-A knockout (SR-A(-/-)) and wild type (SR-A(+/+)) mice with no significant difference between these two groups. SR-A(-/-) hypertensive mice, however, exhibited a marked augmentation of arterial wall thickening and vascular cell proliferation compared with SR-A(+/+) hypertensive mice. M1 macrophage markers were increased whereas M2 macrophage markers were decreased in vascular tissues of SR-A(-/-) mice. Co-culture experiments revealed that more pro-inflammatory cytokines like TNF-α were produced by SR-A(-/-) peritoneal macrophages leading to a stronger proliferation of primary vascular smooth muscle cells in vitro. In addition, SR-A(-/-) macrophages were more prone to lipopolysaccharide-induced M1 differentiation while resisting interleukin-4-induced M2 differentiation. Importantly, transplantation of SR-A(-/-) bone marrow into SR-A(+/+) mice significantly augmented Ang II-induced vascular remodeling. These results show that SR-A is critical for Ang II-induced vascular remodeling by regulating macrophage polarization. Therefore, SR-A may be a useful therapeutic target for the intervention of hypertensive vascular remodeling.
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, People's Republic of China; Department of Cardiology, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, People's Republic of China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Qian
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Ru
authors.initials: R
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Zhuoyun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Bai
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ben
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, People's Republic of China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, People's Republic of China. Electronic address: qichen@njmu.edu.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001808:Blood Vessels / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D006973:Hypertension / Q000503:physiopathology*; D007262:Infusions, Intravenous; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051117:Scavenger Receptors, Class A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018183:Transplantation Chimera / Q000276:immunology / Q000378:metabolism
chemical_list: C495140:Msr1 protein, mouse; D051117:Scavenger Receptors, Class A; D000804:Angiotensin II
keywords: BAY 11-708 (PubChem CID: 24891842); Hypertension; Inflammation; Macrophage polarization; Pentoxifylline (PubChem CID: 4740); SR-A; Teriflunomide (PubChem CID: 4651473); Vascular remodeling