The Role Of Tissue Transglutaminase In Small Intramyocardial Coronary Arteries Remodeling Of Spontaneously Hypertensive Rats

ObjectiveTo explore the role of tissue transglutaminase(tTG)in the progression of Small Intramyocardial Coronary Arteries (SIMCA) remodeling and study the effects and possibile mechanisms of cystamine.Methods12-week-old male SHRs were randomized to 3 groups (all n=8), including untreated SHR group,cystamine high dose(CysH) group,cystamine low dose(CysL) group.Rats of CysH and CysL received cystamine 112mg/kg·d,28mg/kg·d by intraperitoneal injection respectively. Age and sex matched Wistar Kyoto rats were served as control group (WKY,n=8).Systolic blood pressure of rats (SBP) was measured every 2 weeks.After 12 weeks intervention,hemodynamics index of rats were measured before rats being sacrificed. Morphological characteristics were evaluated with HE, Sirus-red,elasticity fibrin and collagen fibrin double staining (P/VB).Wall area (WA), lumen area (LA), and percent wall area (%WA) of SIMCA were assessed with the compute-assisted image analysis system. Immunohisto- chemistry staining was performed to lable tTG and GGEL. TTG was extracted and measured by western blot analysis.Results1 After 12 weeks intervention,SBP of CysH,CysL and SHR groups are all higher than WKY group,there was no difference among CysH,CysL and SHR groups.2 Compared to WKY group, WA and %WA of SIMCA increased and LA decreased in SHR group (P<0.01 for each). WA and %WA in CysH group were lower, but LA was higher than SHR group (P<0.01 for each). Compared to SHR group, %WA and WA were reduced in CysL(P<0.01 for each), but LA was no difference between them.3 The integrated optical density(IOD) of tTG and GGEL in SIMCA of SHR group were remarkably higher than those of WKY group(P<0.01 for each). The IOD of tTG and GGEL of CysH and CysL groups were remarkably lower than those of SHR group(P<0.01 for each),which were higher compared to WKY (P<0.01 for each). Western Blot detected tTG, Group SHR was higher than WKY(P<0.01),after 12-week treatment, tTG was remarkably lower than SHR(P<0.01).4 LVM/BW in SHR group were all higher than WKY. LVM/BW in CysH and CysL were lower than SHR group (P<0.01 for each).5 Mean arterial pressure(MAP),left ventricular systolic pressure(LVSP),left ventri- cular end-diastolic pressure(LVEDP) in Group SHR,CysH and CysL were higher significantly than WKY. MAP, LVSP, and dp/dtmax of CysH and CysL groups were not significantly decreased compared to those of SHR group,except LVEDP (P<0.05).6 CREA and ALT of CysH and CysL groups were much higher than those of WKY and SHR group(P<0.01 for each),though they were both still in normal range. However, ALT, CREA, TC, TG and GLU were no difference between SHR and WKY groups , CysH and CysL groups(P<0.05 for each).Conclusions1 With remodeling of 24-week-old SHR SIMCA,the tTG involved grew, after treatment of inhibitor of cystamine, the remodeling decreased, and the level of tTG went down,the change of GGEL is the same to tTG, Which demonstrated that tTG played a crucial role of SIMCA remodeling in SHR.2 Cys could attenuate myocardial hypertrophy significantly and improve left ventricle diastolic function in SHR.3 CREA and ALT of CysH and CysL groups were much higher than those of WKY and SHR groups(P<0.01 for each),they were both still in normal range. Cys was safe for SHR.