Epxression of matrix metalloproteinases, their inhibitors, and lysyl oxidase in hearts from dogs with end-stage systemic and cardiac diseases

Objective—To compare the degree of transcription of mRNA for matrix metalloproteinases (MMPs), tissue inhibitors (TIMPs), and lysyl oxidase in myocardial samples from dogs with cardiac and systemic diseases and from healthy control dogs.
Sample—Myocardial samples from atria, ventricles, and septum of 8 control dogs, 6 dogs with systemic diseases, 4 dogs with dilated cardiomyopathy (DCM), and 5 dogs with other cardiac diseases.
Procedures—mRNA transcription for MMP-1, -2, -3, -9, and -13; TIMP-1, -2, -3, and -4; and lysyl oxidase was measured via quantitative real-time PCR assay. Histologic examination of the hearts was performed to identify pathological changes.
Results—mRNA transcription in myocardial samples from control dogs, only TIMP-3 and TIMP-4 mRNA was detected, with a significantly higher degree in male versus female dogs. In dogs with systemic and cardiac diseases, all investigated markers were expressed, with a significantly higher degree of mRNA transcription than in control dogs. Furthermore, the degree of transcription for MMP-2, TIMP-1, and TIMP-2 was significantly higher in dogs with DCM than in dogs with systemic diseases and cardiac diseases other than DCM. Transcription was generally greater in atrial than in ventricular tissue, specifically for MMP-2, MMP-13, and lysyl oxidase in atrial tissue from dogs with atrial fibrillation.
Conclusions and Clinical Relevance—The degree of myocardial MMP, TIMP, and lysyl oxidase expression was higher in dogs with heart and systemic diseases than in healthy dogs, suggesting that transcription of these markers is a nonspecific consequence of end-stage diseases. Selective differences in the expression of some markers might reflect specific pathogenic mechanisms and might play a role in disease progression, morbidity and mortality rates, and treatment response.