Inhibition of Gastrin-Releasing Peptide Attenuates Phosphate-Induced Vascular Calcification.

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.

• Authors: Hyun-Joo Park, Yeon Kim, Mi-Kyoung Kim, Jae Joon Hwang, Hyung Joon Kim, Soo-Kyung Bae, Moon-Kyoung Bae
• Journal: Cells (Cells) Vol. 9 Issue 3 (03 17 2020) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 32192106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphates
• Gastrin-Releasing Peptide
• Calcium

Topics

• Animals
• Apoptosis (drug effects)
• Calcium (metabolism)
• Cells, Cultured
• Gastrin-Releasing Peptide (antagonists & inhibitors)
• Muscle, Smooth, Vascular (pathology)
• Myocytes, Smooth Muscle (metabolism, pathology)
• Phosphates (metabolism, pharmacology)
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Vascular Calcification (genetics, metabolism, pathology)