Extracellular matrix accumulation and expression of gelatinases and their tissue inhibitors in a mechanically unloaded heart model / 中国应用生理学杂志

ABSTRACT

<p><b>AIM</b>To investigate the relationship between the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 and ECM accumulation in rat left ventricle in a mechanical unloaded heart model.</p><p><b>METHODS</b>12-week-old male Lewis rats were subjected to abdominal heterotopic heart transplantation to achieve pressure and volume unloading(mechanical unloading). Age and sex matched in situ heart of Lewis rats were used as control. Collagen volume fraction(CVF) was analyzed by picrosiris-red staining plus polarized microscopy. MMP-2 and -9 gelatinolytic activity were measured by gelatin-zymography. mRNA level of MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured by real-time quantitative PCR. TIMP-1 and TIMP-2 protein level were measured by immunoblotting.</p><p><b>RESULTS</b>Myocardial cross-sectional area of transplanted heart was significantly reduced, and accompanied by excessive ECM deposition (CVF 5.22% +/- 1.6% vs. 2.21% +/- 0.9%, P < 0.05) compared to in situ heart. MMP-2 and MMP-9 activity were significantly increased, as well as mRNA level of MMP-2, MMP-9, TIMP-1 and TIMP-2 compared to in situ heart. TIMP-1 and TIMP-2 protein level in mechanically unloaded heart were significantly upregulated compared to in situ heart, especially for TIMP-1.</p><p><b>CONCLUSION</b>Mechanical unloading of left ventricle may lead to excessive ECM deposition, accompanied by imbalance between MMPs and TIMPs system, especially the upregulation of TIMPs.</p>