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Perivascular adipose tissue-derived visfatin is a vascular smooth muscle cell growth factor: role of nicotinamide mononucleotide
- Source :
- Cardiovascular Research. 81:370-380
- Publication Year :
- 2008
- Publisher :
- Oxford University Press (OUP), 2008.
-
Abstract
- Aims Perivascular adipose tissue (PVAT) inhibits vascular smooth muscle cell (VSMC) contraction and stimulates VSMC proliferation by releasing protein factors. The present study was to determine whether visfatin is involved in these paracrine actions of PVAT, and if so, to explore the underlying mechanisms. Methods and results Visfatin was preferentially expressed in Sprague–Dawley rat and monkey aortic PVAT, compared with subcutaneous and visceral adipose tissues. The PVAT-derived visfatin was found to be a VSMC growth factor rather than a VSMC relaxing factor, which was proved by visfatin-specific antibody/inhibitor and direct observation of recombinant visfatin. Exogenous visfatin stimulated VSMC proliferation in a dose- and time-dependent manner via extracellular signal-regulated kinase (ERK 1/2) and p38 signalling pathways. This proliferative effect was further confirmed by enhancement of DNA synthesis and upregulation of proliferative marker Ki-67. Visfatin had no anti-apoptotic effect on normal cultured VSMCs, and it exerted an anti-apoptotic effect only during cell apoptosis induced by H2O2, excluding a role of anti-apoptosis in the visfatin-induced VSMC proliferation. Insulin receptor knockdown did not show any action on the visfatin effect. However, visfatin acted as a nicotinamide phosphoribosyltransferase to biosynthesize nicotinamide mononucleotide (NMN), which mediated proliferative signalling pathways and cell proliferation similar to the visfatin effect. Conclusion Visfatin stimulates VSMC proliferation via NMN-mediated ERK1/2 and p38 signalling. The present study provides a molecular link of visfatin to the paracrine action of PVAT, demonstrates a novel function of visfatin in promoting VSMC proliferation, and reveals NMN as a novel signalling molecule that triggers the proliferative process.
- Subjects :
- Male
MAPK/ERK pathway
medicine.medical_specialty
Vascular smooth muscle
MAP Kinase Signaling System
Physiology
medicine.medical_treatment
Myocytes, Smooth Muscle
Nicotinamide phosphoribosyltransferase
Adipose tissue
Biology
p38 Mitogen-Activated Protein Kinases
Muscle, Smooth, Vascular
Rats, Sprague-Dawley
Mice
chemistry.chemical_compound
Paracrine signalling
Downregulation and upregulation
Physiology (medical)
Internal medicine
medicine
Animals
Extracellular Signal-Regulated MAP Kinases
Nicotinamide Phosphoribosyltransferase
Nicotinamide Mononucleotide
Cell Proliferation
Nicotinamide mononucleotide
Mice, Inbred ICR
Growth factor
Receptor, Insulin
Rats
Ki-67 Antigen
Endocrinology
Adipose Tissue
chemistry
cardiovascular system
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 17553245 and 00086363
- Volume :
- 81
- Database :
- OpenAIRE
- Journal :
- Cardiovascular Research
- Accession number :
- edsair.doi.dedup.....a5b2e34c39b4e436b281544332b58fc6