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Myocardial infarction (Mi) still remains a leading cause of mortality throughout the world. An adverse cardiac remodeling, such as hypertrophy and fibrosis, in non-infarcted area leads to uncompensated heart failure with cardiac dysfunction. We previously demonstrated that canstatin, a c-terminus fragment of type IV collagen α2 chain, exerted anti-remodeling effect against isoproterenolinduced cardiac hypertrophy model rats. In the present study, we examined whether a long-term administration of recombinant canstatin exhibits a cardioprotective effect against the adverse cardiac remodeling in Mi model rats. Left anterior descending artery of male Wistar rats was ligated and recombinant mouse canstatin (20 μg/kg/day) was intraperitoneally injected for 28 days. Long-term administration of canstatin improved survival rate and significantly inhibited left ventricular dilatation and dysfunction after MI. Canstatin significantly inhibited scar thinning in the infarcted area and significantly suppressed cardiac hypertrophy, nuclear translocation of nuclear factor of activated T-cells, interstitial fibrosis and increase of myofibroblasts in the non-infarcted area. Canstatin significantly inhibited transforming growth factor-β1-induced differentiation of rat cardiac fibroblasts into myofibroblasts. The present study for the first time demonstrated that long-term administration of recombinant canstatin exerts cardioprotective effects against adverse cardiac remodeling in MI model rats. Myocardial infarction (MI), an ischemic heart disease, induced by occlusion of coronary artery remains a leading cause of mortality throughout the world 1,2. Ischemic injury by coronary arterial occlusion evokes massive cardiomyocyte death, which in turn forms an infarcted area 3,4. In the early phase of MI, cardiac fibroblasts contribute to repair the infarcted area through the activation of biological functions, such as proliferation, migration and differentiation into myofibroblasts 5. Myofibroblasts characterized by an abundant expression of α-smooth muscle actin (α-SMA) play a pivotal role during scar formation in the infarcted area through the synthesis of structural extracellular matrix (ECM) proteins 3. Although maturation of scar tissue is important to maintain cardiac structure and function 6 , insufficient scar formation causes scar thinning, cardiac dysfunction and/or cardiac rupture 3. The infarct size is an important in prognosis and mortality in MI patients 7. On the other hand, the degree of cardiac remodeling in non-infarcted ventricles is also crucial in the prognosis of MI 4. An adaptive cardiac hypertrophy in the non-infarcted area compensates the reduction of cardiac contractility 8. In the chronic phase of MI, an interstitial fibrosis in the non-infarcted area is mainly induced by activated myofibroblasts, which increases ventricular stiffness 9. The interstitial fibrosis and pathological cardiac hypertrophy result in eccentric hypertrophy with left ventricular (LV) wall thinning and dilatation 4,9. The scar thinning in...

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