Ramasamy Ravichandran, Schmidt Ann Marie
Diabetes Research Program, Division of Endocrinology, Department of Medicine, NYU School of Medicine, 550 First Avenue, Smilow 901, New York, NY, 10016, USA.
Curr Heart Fail Rep. 2012 Jun;9(2):107-16. doi: 10.1007/s11897-012-0089-5.
The receptor for advanced glycation end products (RAGE) is expressed in the heart in cardiomyocytes, vascular cells, fibroblasts, and in infiltrating inflammatory cells. Experiments in murine, rat, and swine models of injury suggest that RAGE and the ligands of RAGE are upregulated in key injuries to the heart, including ischemia/reperfusion injury, diabetes, and inflammation. Pharmacological antagonism of RAGE or genetic deletion of the receptor in mice is strikingly protective in models of these stresses. Data emerging from human studies suggest that measurement of levels of RAGE ligands or soluble RAGEs in plasma or serum may correlate with the degree of heart failure. Taken together, the ligand-RAGE axis is implicated in heart failure and we predict that therapeutic antagonism of RAGE might be a unique target for therapeutic intervention in this disorder.
晚期糖基化终末产物受体（RAGE）在心脏的心肌细胞、血管细胞、成纤维细胞以及浸润的炎性细胞中表达。在小鼠、大鼠和猪的损伤模型中进行的实验表明，在心脏的关键损伤（包括缺血/再灌注损伤、糖尿病和炎症）中，RAGE及其配体的表达上调。在这些应激模型中，对小鼠进行RAGE的药理学拮抗或受体的基因敲除具有显著的保护作用。来自人体研究的数据表明，测量血浆或血清中RAGE配体或可溶性RAGE的水平可能与心力衰竭的程度相关。综上所述，配体-RAGE轴与心力衰竭有关，我们预测RAGE 的治疗性拮抗可能是针对这种疾病进行治疗干预的独特靶点。
