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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Fibroblast growth factor 21 plays an inhibitory role in vascular calcification in vitro through OPG/RANKL system
Fangying Cao1, Xiaoxiao Liu1, Xiangrong Cao2
1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
Abstract:
Vascular calcification is prevalent and associated with adverse outcome without available therapy. The benefits of fibroblast growth factor (FGF)-21 on metabolism and atherosclerosis make it a promising therapeutic agent for vascular calcification. We investigated the effects of FGF21 on vascular smooth muscle cell (VSMC) calcification by culturing rat VSMCs in a calcifying medium for 9days. FGF21 markedly attenuated mineral deposition and apoptosis at the indicated time points. In the presence of FGF21, the expression levels of osteoblastic protein including bone morphogenic protein-2, alkaline phosphatase(ALP), runt-related transcription factor(RUNX)-2 and nuclear factor-kappa B ligand (RANKL) were down-regulated, whereas the expression of osteoprotegerin (OPG) increased. Knockdown of OPG significantly impaired inhibition of FGF21 on apoptosis and the expression of pro-apoptotic genes including caspase-3 and Bax and osteoblastic -promoting markers including ALP, RUNX-2 and RANKL. Furthermore, FGF21 facilitated the phosphoryl of AKT but suppressed P38, while OPG knockdown attenuated the effects. LY29400 (inhibitor of PI3K) abrogated the activation of PI3K/AKT and SB203580 (inhibitor of P38) abolished the inhibition of FGF21 on P38, while alteration was observed in the expression of RUNX-2. FGF21 inhibited VSMCs calcification via OPG/RANKL system, and through P38 andPI3K/AKT pathways.
Insights
Fibroblast growth factor (FGF)-21 effectively reduces vascular calcification by decreasing mineral deposition and apoptosis in vascular smooth muscle cells (VSMCs). FGF21 acts through the OPG/RANKL system and PI3K/AKT and p38 pathways.
Area of Science:
- Biomedical Science
- Cell Biology
- Vascular Biology
Background:
- Vascular calcification is a common condition linked to poor outcomes, with limited therapeutic options.
- Fibroblast growth factor (FGF)-21 shows potential for treating vascular calcification due to its metabolic and anti-atherosclerotic benefits.
Purpose of the Study:
- To investigate the therapeutic effects of FGF21 on vascular smooth muscle cell (VSMC) calcification.
- To elucidate the molecular mechanisms underlying FGF21's action in preventing VSMC calcification.
Main Methods:
- Rat VSMCs were cultured in a calcifying medium for 9 days.
- FGF21 treatment was applied, and its effects on mineral deposition, apoptosis, and gene/protein expression were analyzed.
- Key signaling pathways (PI3K/AKT, p38) and molecular markers (OPG, RANKL, ALP, RUNX-2) were assessed.
Main Results:
- FGF21 significantly reduced mineral deposition and apoptosis in VSMCs.
- FGF21 downregulated osteoblastic markers (BMP-2, ALP, RUNX-2, RANKL) and upregulated osteoprotegerin (OPG).
- FGF21 promoted AKT phosphorylation while suppressing p38; OPG knockdown reversed these effects and impaired FGF21's anti-apoptotic and anti-calcific actions.
Conclusions:
- FGF21 inhibits VSMC calcification by modulating the OPG/RANKL system.
- The protective effects of FGF21 involve the regulation of p38 and PI3K/AKT signaling pathways.
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