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Updated: May 23, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Ghrelin attenuates the osteoblastic differentiation of vascular smooth muscle cells through the ERK pathway
Qiu-Hua Liang1, Yi Jiang, Xiao Zhu
1Institute of Metabolism and Endocrinology, the Second Xiang-Ya Hospital, Central South University, Changsha, People's Republic of China.
Abstract:
Vascular calcification results from osteoblastic differentiation of vascular smooth muscle cells (VSMCs) and is a major risk factor for cardiovascular events. Ghrelin is a newly discovered bioactive peptide that acts as a natural endogenous ligand of the growth hormone secretagog receptor (GHSR). Several studies have identified the protective effects of ghrelin on the cardiovascular system, however research on the effects and mechanisms of ghrelin on vascular calcification is still quite rare. In this study, we determined the effect of ghrelin on osteoblastic differentiation of VSMCs and investigated the mechanism involved using the two universally accepted calcifying models of calcifying vascular smooth muscle cells (CVSMCs) and beta-glycerophosphate (beta-GP)-induced VSMCs. Our data demonstrated that ghrelin inhibits osteoblastic differentiation and mineralization of VSMCs due to decreased alkaline phosphatase (ALP) activity, Runx2 expression, bone morphogenetic protein-2 (BMP-2) expression and calcium content. Further study demonstrated that ghrelin exerted this suppression effect via an extracellular signal-related kinase (ERK)-dependent pathway and that the suppression effect of ghrelin was time dependent and dose dependent. Furthermore, inhibition of the growth hormone secretagog receptor (GHSR), the ghrelin receptor, by siRNA significantly reversed the activation of ERK by ghrelin. In conclusion, our study suggests that ghrelin may inhibit osteoblastic differentiation of VSMCs through the GHSR/ERK pathway.
Insights
Ghrelin, a bioactive peptide, inhibits vascular calcification by preventing smooth muscle cell differentiation. This occurs through the growth hormone secretagog receptor (GHSR) and extracellular signal-related kinase (ERK) pathway.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Cellular Biology
Background:
- Vascular calcification, driven by smooth muscle cell osteoblastic differentiation, is a key cardiovascular risk factor.
- Ghrelin, a peptide hormone, has known cardiovascular protective effects, but its role in vascular calcification is underexplored.
Purpose of the Study:
- To investigate the effects of ghrelin on vascular smooth muscle cell (VSMC) osteoblastic differentiation.
- To elucidate the underlying molecular mechanisms of ghrelin's action in vascular calcification.
Main Methods:
- Utilized calcifying vascular smooth muscle cells (CVSMCs) and beta-glycerophosphate (beta-GP)-induced VSMCs.
- Assessed alkaline phosphatase (ALP) activity, Runx2 and bone morphogenetic protein-2 (BMP-2) expression, and calcium content.
- Investigated the involvement of the extracellular signal-related kinase (ERK) pathway and the growth hormone secretagog receptor (GHSR) using siRNA.
Main Results:
- Ghrelin significantly inhibited VSMC osteoblastic differentiation and mineralization.
- Observed decreased ALP activity, Runx2, BMP-2 expression, and calcium content in response to ghrelin.
- Demonstrated that ghrelin's suppressive effect is mediated through the GHSR/ERK pathway in a time- and dose-dependent manner.
Conclusions:
- Ghrelin effectively inhibits osteoblastic differentiation and mineralization of VSMCs.
- The GHSR/ERK signaling pathway is crucial for ghrelin's inhibitory effects on vascular calcification.
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