Clin Hypertens.  2016 ;22(1):2. 10.1186/s40885-016-0037-x.

Mesoglycan attenuates VSMC proliferation through activation of AMP-activated protein kinase and mTOR

Affiliations
  • 1Department of Pharmacology, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, Nam-Gu, Daegu 42415, Republic of Korea. hcchoi@med.yu.ac.kr
  • 2Department of Thoracic and Cardiovascular Surgery, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, Nam-Gu, Daegu 42415, Republic of Korea.
  • 3Smart-aging Convergence Research Center, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, Daegu 42125, Republic of Korea.

Abstract

BACKGROUND
Vascular smooth muscle cells (VSMC) proliferation contributes significantly to intimal thickening in atherosclerosis and restenosis diseases. Platelet derived growth factor (PDGF) has been implicated in VSMC proliferation though the activation of multiple growth-promoting signals. Mesoglycan, a natural glycosaminoglycans preparation, is reported to show vascular protective effect. However, the mechanisms by which mesoglycan inhibits proliferation of VSMC are not fully understood. Here, we investigated whether mesoglycan exert therapeutic effect via AMP-activated protein kinase (AMPK) and its underlying mechanism.
METHODS
We cultured VSMC with increasing doses of mesoglycan. AMPK activation was measured by western blot analysis and cell proliferation was measured by flow cytometry.
RESULTS
Mesoglycan dose- and time- dependently increased the phosphorylation of AMPK (Thr172) and its upstream target, LKB1 (Ser428) and its downstream, ACC (Ser79) in VSMCs. Mesoglycan also blocked the PDGF-stimulated cell cycle progression through the G0/G1 arrest. AMPK DNalpha1, AMPK DNalpha2 or AMPK siRNA reduced the mesoglycan-mediated inhibition of VSMC proliferation. AMPK signaling activated by mesoglycan regulates mTOR phosphorylation which closely related to cell proliferation.
CONCLUSION
These data suggest that mesoglycan-induced AMPK activation suppress the VSMC proliferation via mTOR-dependent mechanism and mesoglycan may have beneficial effects on vascular proliferative disorders such as atherosclerosis.

Keyword

Mesoglycan; AMPK; VSMC; mTOR; Proliferation

MeSH Terms

AMP-Activated Protein Kinases*
Atherosclerosis
Blotting, Western
Cell Cycle
Cell Proliferation
Flow Cytometry
Glycosaminoglycans
Muscle, Smooth, Vascular
Phosphorylation
Platelet-Derived Growth Factor
RNA, Small Interfering
AMP-Activated Protein Kinases
Glycosaminoglycans
Platelet-Derived Growth Factor
RNA, Small Interfering
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