Intermedin inhibits vascular calcification by increasing the level of matrix γ-carboxyglutamic acid protein

Abstract

Reduced endogenous IMD levels are associated with increased mineralization in vivo, and administration of IMD inhibits VC development by increasing cMGP levels. IMD may be an endogenous vasoprotective factor for VC.

Adrenomedullin up-regulates osteopontin and attenuates vascular calcification via the cAMP/PKA signaling pathway

“…OPN is a potent physiological inhibitor of mineralization − it prevents ectopic calcium deposition and is a potent inducible inhibitor of VC [42] . Previous studies have shown that there are increased OPN protein levels in patients with signs of VC and in several VC models in vivo and in vitro [15,[17][18][19]43] ; additionally, a decrease in OPN expression enhances VC both in vivo and in vitro [21,22] . Furthermore, re-expression of OPN in OPN -/-VSMCs rescues the calcification phenotype of these cells [22] .…”

“…During VC, as VSMCs switch to an osteoblast-like phenotype that expresses BMPs, some proteins, such as OPN and cMGP, are important inhibitors of VC [12][13][14][15] . OPN is a potent physiological inhibitor of mineralization − it prevents ectopic calcium deposition and is a potent inducible inhibitor of VC [42] .…”

“…The VSMCs were fixed, permeabilized, blocked as previously described [15] , and subsequently stained with an anti-alphaactin antibody (1:400 mouse anti-rat alpha-actin, Sigma).…”

“…This osteoblast-like phenotype is characterized by increased alkaline phosphatase (ALP) activity, matrix vesicle formation, and overexpression of bone morphogenetic proteins (BMPs), such as BMP-2, as well as bone matrix proteins, such as osteopontin (OPN), osteonectin, and osteocalcin [4,[7][8][9][10][11] . However, some BMPs, such as OPN and gamma-carboxyglutamic acid (Gla) protein (cMGP), are endogenous inhibitors of VC [12][13][14][15] . OPN is a phosphorylated glycoprotein generated or secreted by osteoblasts, osteoclasts, macrophages, T cells, hematopoietic cells, VSMCs, fibroblasts, and myocardial cells [16] .…”

“…Recent studies have also demonstrated that paracrine/autocrine factors help maintain circulatory homeostasis and mediate the pathogenesis of cardiovascular disease. Among these factors, vasoactive peptides, such as adrenomedullin (ADM), intermedin, ghrelin, parathyroid hormone-related peptide, and C-type natriuretic peptide, are endogenous factors that inhibit VC [15,[24][25][26][27] . However, endothelin and angiotensin II have opposite effects [28,29] .…”