Advanced glycation end-product Nɛ-carboxymethyl-Lysine accelerates progression of atherosclerotic calcification in diabetes

High Glucose Concentration Does Not Modulate the Formation of Arterial Medial Calcification in Experimental Uremic Rats

“…4). Expression of RAGE was examined by immunohistochemistry, because the AGE-RAGE axis has been shown to play an important role in vascular calcification in type 2 diabetes [10,11,12,13]. As shown in figure 3, RAGE expression was increased in the aorta of hyperglycemic, uremic/hyperglycemic and uremic rats, but not in the aorta of control rats.…”

“…Overexpression of RAGE has been shown to not only induce osteogenic differentiation, but also decrease SMC differentiation marker genes in cultured SMCs [12]. In addition, daily injections of N ε -carboxymethyl-lysine, a major immunogen of AGEs, accelerated the progression of atherosclerotic calcification in diabetic mice fed a high-fat diet [13]. Results of these studies suggest an importance of the AGE-RAGE axis for arterial medial calcification.…”

Balanced Mineralization in the Arterial System

“…21, 22 A recent study has also shown that carboxymethyl-lysine, a major immunogen of AGEs, accelerates atherosclerotic calcification under high-lipid conditions through increased osteogenic differentiation of aortic smooth muscle cells (SMCs) with upregulation of bone-related genes. 23 Furthermore, AGEs induce the phosphorylation of p38 MAPK through the receptor for AGE and accelerate the calcification of vascular SMCs (VSMCs). 24 A receptor activator of the nuclear factor κ B ligand (RANKL)-RANK/osteoprotegerin (OPG) signaling has also been shown to play a major role in arterial calcification.…”

Advanced glycation end products promote human aortic smooth muscle cell calcification in vitro via activating NF-κB and down-regulating IGF1R expression

“…Recent data have demonstrated that AGEs accelerate the progression of diabetic atherosclerosis and vascular calcification [20][21][22] . AGEs act through their receptor RAGE, and increase apoptosis and the induction of alkaline phosphatase (ALP) and osteogenic genes [12,23] , including CBFα1, a key regulatory transcription factor critical for osteoblast differentiation, and osteocalcin, which is a very specific protein indicative of osteoblast activity. CBFα1 knockout mice fail to form mineralized bone [24] and exhibit low ALP activity and osteocalcin expression.…”