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
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