[Myocardial matrix metalloproteinases activities in mice with viral myocarditis and their relationship with cardiac function and myocardial collagen amount].
OBJECTIVE
To investigate the dynamic changes of myocardial matrix metalloproteinases (MMPs) activities in mice with viral myocarditis (VM) and their relationships with cardiac function and myocardial collagen amount and to explore the role of MMPs in the pathologic lesion of VM.


METHODS
Sixty-five six-week-old male DBA/2 mice were obtained from the Chinese Academy of Medical Sciences. They were divided into two groups randomly. Mice in infected group (n=50) were inoculated intraperitoneally with 0.14 ml of coxsackievirus B3 (CVB3, Nancy strain). Control mice (n=15) were inoculated intraperitoneally with 0.14 ml of Eagle's solution. Eight infected mice were sacrificed on day 3, 7, 10, 21 and 30, respectively and fifteen control mice were killed on day 30 after inoculation. Total protein concentration was determined according to the method of Bradford, while MMPs activities were measured with SDS-PAGE type substrate gels embedded with type I gelatin (zymography). Echocardiographic studies were performed under anesthesia with 3% chloralhydrate intraperitoneally (0.01-0.015 ml/g). Cardiac systolic function indexes, such as peak velocity of aorta (Vp) and flow velocity integral of aorta (Vi) were determined by echocardiography. Histological cross sections of hearts were stained with hematoxylin-eosin and myocardial histopathologic scores were counted under optical microscope. Myocardial collagen amount was measured by determination of hydroxyproline quantification.


RESULTS
In virus-infected mice, both MMP-2 and MMP-9 activities were increased significantly compared with those in controls and reached the peak on day 10 (P < 0.01). On day 10, cardiac systolic function indexes (Vp and Vi) were all significantly lower than those at other stages after virus inoculation and in control group (P < 0.05). There was no obvious elevation in myocardial collagen amount in mice with VM at acute stage (P > 0.05). While the myocardial collagen amount in infected group at recovery stage (on day 21 and 30) increased significantly compared with controls. MMP-2 and MMP-9 activities positively correlated with myocardial histopathological scores, respectively (r =0.801, 0.821 P < 0.01), while they negatively correlated with Vp (r = -0.649, -0.683, P < 0.01) and Vi, respectively (r = -0.711, -0.755, P < 0.01). However, Vp and Vi negatively correlated with myocardial histopathological scores (r = -0.756, -0.584, P < 0.01).


CONCLUSIONS
In mice with VM, the activities of myocardial MMP-2 and MMP-9 at acute stage increased significantly, then myocardial collagen amount elevated in recovery stage. These changes were associated with myocardial remodeling and cardiac dysfunction. Myocardial MMP activities are important markers of myocardial pathologic lesion. They are of value in the evaluation of the severity of myocardial damage and cardiac dysfunction in mice with VM.
Meng
Xiao-Hui
XH
Shangdong Provincial Hospital, Jinan 250021, China.
Wang
Yi
Y
Zhuang
Jian-Xin
JX
Chen
Yao
Y
Jin
You-Peng
YP
Han
Xiu-Zhen
XZ
Wang
Yu-Lin
YL
D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003384:Coxsackievirus Infections / Q000150:complications; D004195:Disease Models, Animal; D004452:Echocardiography; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D009205:Myocarditis / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D013599:Systole; D018754:Ventricular Dysfunction / Q000000981:diagnostic imaging / Q000503:physiopathology; D020257:Ventricular Remodeling
D003094:Collagen; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9