Abstract
Vascular calcification is the pathological deposition of calcium/phosphate in the vascular system and is closely associated with cardiovascular morbidity and mortality. Here, we investigated the role of gastrin-releasing peptide (GRP) in phosphate-induced vascular calcification and its potential regulatory mechanism. We found that the silencing of GRP gene and treatment with the GRP receptor antagonist, RC-3095, attenuated the inorganic phosphate-induced calcification of vascular smooth muscle cells (VSMCs). This attenuation was caused by inhibiting phenotype change, apoptosis and matrix vesicle release in VSMCs. Moreover, the treatment with RC-3095 effectively ameliorated phosphate-induced calcium deposition in rat aortas ex vivo and aortas of chronic kidney disease in mice in vivo. Therefore, the regulation of the GRP-GRP receptor axis may be a potential strategy for treatment of diseases associated with excessive vascular calcification.
Highlights
Vascular calcification refers to the pathological deposition of calcium and phosphate minerals in the vascular system [1]
Western blot analysis showed that gastrin-releasing peptide (GRP) and GRP receptor expression levels significantly increased in the vascular smooth muscle cells (VSMCs) under calcifying medium (Figure 1e)
Endothelial cells and VSMCs are associated with the pathological processes involved in atherosclerosis, including endothelial dysfunction, vascular inflammation, VSMC proliferation and migration and vascular calcification [32,33]
Summary
Vascular calcification refers to the pathological deposition of calcium and phosphate minerals in the vascular system [1]. It is closely associated with aging, atherosclerosis and metabolic disorders, such as diabetes mellitus and chronic kidney disease [2,3]. Potential mechanisms of phosphate-induced vascular calcification are apoptosis, matrix vesicle release and osteogenic/chondrogenic conversion of vascular smooth muscle cells (VSMCs) [6,7,8], making vascular calcification is a tightly regulated process, similar to bone formation. Gastrin-releasing peptide (GRP), a member of bombesin-like peptides, has been clearly implicated in several physiological and pathological processes, including exocrine and endocrine secretions, gastrointestinal tract motility, smooth muscle contraction and cell proliferation in normal and cancerous tissues [9,10].
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