The accelerated post-infarction progression of cardiac remodelling is associated with genetic changes in an untreated streptozotocin-induced diabetic rat model.
OBJECTIVE
The mechanism by which diabetes mellitus exacerbates myocardial injury and the incidence of heart failure after acute myocardial infarction (AMI), remains unclear. We studied the severity of cardiac dysfunction and time-dependent gene expression in a hyperglycaemic rat model with AMI.


RESULTS
The diabetic model was produced by injection of streptozotocin in Sprague-Dawley rats. Ten weeks after induction of diabetes, AMI was induced by ligation of the left anterior descending coronary artery. Cardiac function and left ventricular (LV) dimensions were evaluated using two-dimensional echocardiography. Structural changes were assessed by histological examination. Gene expression profile was documented by using affymetrix genechip U230 2.0 array and real time-PCR. During 56 days post-AMI, lower survival rates, worse LV function, more severe fibrosis, and larger LV diameters were identified in diabetic rats compared with non-diabetic rats. A total 1221 genes involved in processes, such as glucose metabolism, fatty acid metabolism, extracellular matrix, and apoptosis, were found to be differentially expressed between diabetic and non-diabetic rats, of these 770 were up-regulated and 451 down-regulated. Up-regulation of the genes was found 1-2 weeks earlier in diabetic rats than in non-diabetic rats.


CONCLUSIONS
The present data suggest that hyperglycaemia up-regulates remodelling-related genes, which may be responsible for the worse outcomes in diabetics than in non-diabetics after AMI.
Center of Coronary Heart Disease, Cardiovascular Institute and Fu-Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100037, PR China.
Guang-Yuan
GY
Song
Yong-Jian
YJ
Wu
Yue-Jin
YJ
Yang
Jian-Jun
JJ
Li
Hong-Liang
HL
Zhang
Han-Jun
HJ
Pei
Zhen-Yan
ZY
Zhao
Zeng-Hua
ZH
Zeng
Ru-Tai
RT
Hui
D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D015150:Echocardiography, Doppler; D005355:Fibrosis / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D046228:Microarray Analysis; D046529:Microscopy, Electron, Transmission; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D009218:Myosins / Q000235:genetics* / Q000378:metabolism; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin; D016019:Survival Analysis; D015854:Up-Regulation; D020257:Ventricular Remodeling / Q000235:genetics* / Q000502:physiology
D000199:Actins; D013311:Streptozocin; D009218:Myosins