Adipolin/CTRP12 protects against pathological vascular remodelling through suppression of smooth muscle cell growth and macrophage inflammatory response
Autor: | Mari Kaneko, Takaya Abe, Rei Shibata, Satoko Hayakawa, Mikito Takefuji, Kazuhiro Matsuo, Toyoaki Murohara, Hayato Ogawa, Shukuro Yamaguchi, Takashi Enomoto, Masanori Ito, Mizuho Hiramatsu-Ito, Hiroshi Kawanishi, Takahiro Kambara, Daisuke Yuasa, Noriyoshi Kanemura, Naoya Otaka, Koji Ohashi, Noriyuki Ouchi |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Vascular smooth muscle Platelet-derived growth factor Physiology medicine.medical_treatment Adipose tissue Smad2 Protein 030204 cardiovascular system & hematology Muscle Smooth Vascular Mice chemistry.chemical_compound 0302 clinical medicine Medicine Phosphorylation Mice Knockout Neointimal hyperplasia biology Femoral Artery Tumor necrosis factor alpha Inflammation Mediators Cardiology and Cardiovascular Medicine Platelet-derived growth factor receptor Signal Transduction medicine.medical_specialty Myocytes Smooth Muscle Vascular Remodeling Vascular remodelling in the embryo 03 medical and health sciences Adipokines Neointima Physiology (medical) Internal medicine Human Umbilical Vein Endothelial Cells Animals Humans Cell Proliferation business.industry Growth factor Receptor Transforming Growth Factor-beta Type II Vascular System Injuries medicine.disease Mice Inbred C57BL Disease Models Animal HEK293 Cells RAW 264.7 Cells 030104 developmental biology Endocrinology chemistry Macrophages Peritoneal biology.protein business |
Zdroj: | Cardiovascular Research. 116:237-249 |
ISSN: | 1755-3245 0008-6363 |
DOI: | 10.1093/cvr/cvz074 |
Popis: | AimsSecreted factors produced by adipose tissue are involved in the pathogenesis of cardiovascular disease. We previously identified adipolin, also known as C1q/TNF-related protein 12, as an insulin-sensitizing adipokine. However, the role of adipolin in vascular disease remains unknown. Here, we investigated whether adipolin modulates pathological vascular remodelling.Methods and resultsAdipolin-knockout (APL-KO) and wild-type (WT) mice were subjected to wire-induced injury of the femoral artery. APL-KO mice showed increased neointimal thickening after vascular injury compared with WT mice, which was accompanied by an enhanced inflammatory response and vascular cell proliferation in injured arteries. Adipolin deficiency also led to a reduction in transforming growth factor-β (TGF-β) 1 protein levels in injured arteries. Treatment of cultured macrophages with adipolin protein led to a reduction in lipopolysaccharide-stimulated expression of inflammatory mediators, including tumour necrosis factor (TNF)-α, interleukin (IL) 6, and monocyte chemotactic protein (MCP)-1. These effects were reversed by inhibition of TGF-β receptor II (TGF-βRII)/Smad2 signalling. Adipolin also reduced platelet-derived growth factor (PDGF)-BB-stimulated proliferation of vascular smooth muscle cells (VSMCs) through a TGF-βRII/Smad2-dependent pathway. Furthermore, adipolin treatment significantly increased TGF-β1 concentration in media from cultured VSMCs and macrophages.ConclusionThese data indicate that adipolin protects against the development of pathological vascular remodelling by attenuating macrophage inflammatory responses and VSMC proliferation. |
Databáze: | OpenAIRE |
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