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Isolation and Characterization of Primary Rat Valve Interstitial Cells: A New Model to Study Aortic Valve Calcification
Published on: November 20, 2017
BFGF attenuates aortic valvular interstitial cell calcification by inhibiting endoplasmic reticulum stress-mediated
Gao Yuan1, Li Ning2, Xue Qing1
1Department of Cardiovascular Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
Insights
Basic fibroblast growth factor (BFGF) reduces calcific aortic valve disease (CAVD) by inhibiting osteogenic differentiation and apoptosis in valvular interstitial cells. This protective effect involves PI3K/Akt and ERK1/2 pathways.
Area of Science:
- Cardiovascular Biology
- Cellular Mechanisms
- Translational Medicine
Background:
- Calcific aortic valve disease (CAVD) is a progressive condition with limited therapeutic options.
- The role of basic fibroblast growth factor (BFGF) in CAVD pathogenesis and its underlying mechanisms remain unclear.
- BFGF has shown potential cardiovascular protective effects in previous studies.
Purpose of the Study:
- To investigate the therapeutic potential of BFGF in mitigating CAVD.
- To elucidate the molecular mechanisms by which BFGF affects valvular interstitial cell (VIC) osteogenic differentiation and apoptosis.
- To assess the efficacy of BFGF in a preclinical rat model of CAVD.
Main Methods:
- Porcine VICs were isolated and treated with osteogenic induced medium (OIM) and BFGF.
- Protein expression was analyzed using Western blot; apoptosis was assessed via flow cytometry.
- A rat CAVD model was established and treated with exogenous BFGF, with assessments including echocardiography and Alizarin red staining.
Main Results:
- BFGF levels were elevated in CAVD patients' aortic valves and serum.
- Exogenous BFGF administration attenuated CAVD progression in vivo.
- BFGF suppressed osteogenic differentiation, endoplasmic reticulum stress (ERS), and apoptosis in VICs, effects abolished by PI3K/Akt and ERK1/2 pathway inhibitors.
Conclusions:
- BFGF alleviates VIC calcification and CAVD progression.
- The protective effects of BFGF are mediated by the inhibition of ERS-induced apoptosis.
- Activation of PI3K/Akt and ERK1/2 signaling pathways plays a crucial role in BFGF's therapeutic action, suggesting BFGF as a potential CAVD treatment.
Abstract:
The potential protective effect of basic fibroblast growth factor (BFGF) on the cardiovascular system has been proposed previously, however, its effect on calcific aortic valve disease (CAVD) and underlying mechanisms have not been elucidated. The valvular interstitial cell (VIC) were isolated from porcine aortic valve leaflets. To investigate the effect of BFGF on osteogenic differentiation of VIC, the osteogenic induced medium (OIM) and BFGF were added. The protein expression level was detected by Western blot, and apoptosis was determined by flow cytometry. The effect of BFGF on CAVD process in vivo was assessed by a rat CAVD model, which was identified by echocardiography and Alizarin red staining. The expression level of BFGF in the aortic valve and serum were significantly upregulated in CAVD patients compared to control group. In addition, exogenous BFGF injection attenuates CAVD process in vivo. The protein markers of osteogenic differentiation, endoplasmic reticulum stress (ERS), and apoptosis were significantly upregulated by culture with OIM. On the contrary, the aforementioned proteins were suppressed after adding 100 ng/mL of BFGF. Inhibition of PI3K/Akt and ERK1/2 pathways by specific inhibitors abolished the protective effect of BFGF. In conclusion, BFGF could alleviate the VIC calcification by inhibiting ERS-mediated apoptosis, which is partly regulated by activation of the PI3K/Akt and ERK1/2 signaling pathways. BFGF may provide a potential avenue for CAVD therapy.
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