1.Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-beta1 expression and fibrosis in minipigs with ischemia-reperfusion injury.
Lin LU ; Qi ZHANG ; Yan XU ; Zheng-bin ZHU ; Liang GENG ; Ling-jie WANG ; Cao JIN ; Qiu-jing CHEN ; Ann Marie SCHMIDT ; Wei-feng SHEN
Chinese Medical Journal 2010;123(5):594-598
BACKGROUNDThe cardioprotective effects of soluble receptor for advanced glycation end-products (sRAGE) have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion (I/R) injury.
METHODSTen male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE (sRAGE group, n = 5) or saline (control group, n = 5). Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor (TGF)-beta1 was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining.
RESULTSAs compared with the baseline values in the control animals, left ventricular end-diastolic volume (from (19.5 +/- 5.1) to (32.3 +/- 5.6) ml, P < 0.05) and end-systolic volume (from (8.3 +/- 3.2) to (15.2 +/- 4.1) ml, P< 0.05) were significantly increased, whereas ejection fraction was decreased (from (61.6 +/- 13.3)% to (50.2 +/- 11.9)%, P < 0.05). No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-beta1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group (both P< 0.01). Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals (P < 0.05).
CONCLUSIONIntra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-beta1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.
Animals ; Echocardiography ; Fibrosis ; Humans ; Male ; Myocardial Infarction ; etiology ; Myocardium ; metabolism ; pathology ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; administration & dosage ; Reperfusion Injury ; Swine ; Swine, Miniature ; Transforming Growth Factor beta1 ; genetics ; Ventricular Remodeling
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