Relationship between collagen Ⅰ,MMP-2 and TIMP-2 gene expression and atrial fibrosis and fibrillation during heart failure in dogs / 中华老年医学杂志

ABSTRACT

Objective To study the relationship between Couagen Ⅰ,MMP-2,TIMP-2 gene expression and atrial fibrosis during heart failure(HF)in dog.Methods Fourteen dogs were used and randomized into HF induced by ventricular tachypacing and control group.Burst atrial pacing was used to induce atrial fibrillation(AF).And the mRNA and protein level of collagen Ⅰ,MMP-2 and TIMP-2 were detected by RT-PCR and immunohistochemical technique.Tissue samples were stained with Mallory trichrome.Results Left ventricular ejection fraction (LVEF) decreased from (67.4? 6.0)% to (29.2?7.8)%,the inducible rate of AF(7/7 vs 2/7) and sustained AF(5/7 vs 0/7) increased and duration of AF stabeatrial fibrillation(SAF) [(462.12?181.43)s vs(0.57?0.57) s] prolonged significantly in HF group.Atrial fibrous tissue content and atrial size of HF group were significantly greater than the controls dogs(268.8% in lefe atria and 190.3% in right atria).The mRNA and protein level of collagen Ⅰ(56.2% and 132.2% in lefe atria,37.4% and 78.0% in right atria)and MMP-2 (100.0% and 115.7% in lefe atria,65.7% and 96.8% in right atria) increased evidently in both lefe atria and right atria,TIMP-2 mRNA decreased 46.3% in lefe atria and had no change in right atria and that its protein had no change in both atrium,whereas the ratio of MMP-2/ TIMP-2 of mRNA and protein increased markedly in both lefe atria (285.3% and 148.8%)and right atria (106.1% and 134.7%)of HF group.SAF had a positive correlation with fibrosis and the gene level of collagen Ⅰ in lefe atria,the ratio of MMP-2/TIMP-2 had a positive correlation with fibrosis and collagen Ⅰ gene level in lefe atria during HF.Conclusions The changes of collagen Ⅰ,MMP-2 and TIMP-2 gene expression appear to be a molecular mechanism of AF, and the molecular remodeling of collagen Ⅰ induced by regulation unbalance of MMP-2/TIMP-2 appears to be an important mechanism of atrial fibrosis during HF.