Differential Expression of Matrix Metalloproteinases 1 and 9 and Tissue Inhibitors 1 and 2 in Mitral Valve Disease—Indicators for Progression of the Disease?

Objective: Several previous studies suggested a potent role of matrix metalloproteinase (MMP) as underlying mechanism in native heart valve degeneration. Pathological mechanism and causes of mitral valve insufficiency (MI) despite infective endocarditis remain unclear, but expression of MMP and Tissue Inhibitors (TIMP) could result in a staging for progression of MI. In an immunohistological study, the expression of MMPs 1 and 9 and TIMPs 1 and 2 were studied, as well.

Methods: Thirty-three patients with reduced ejection fraction (mean age 67.8; male/female ratio 1.2 (54.5% and female 45.5%) with mitral valve disease of different origin undergoing mitral valve reconstructive surgery. Herein, 8 with endocarditis and 25 with degenerative myxoid (n = 14)/sclerotic valve disease (n = 10). Immunohistochemical staining of mitral valve samples was performed for protein expression of MMP 1 (Clone MAB 3307, Merck Millipore), MMP 9 (Clone 15W2, Novocastra Inc.) and the TIMP 1 (Clone VT7, Dako) and TIMP 2 (Clone 46E5, Novocastra Inc.). Microscopic evaluation was performed by a staining score from 1 to 3. Statistic procedure was performed according rank-sum test (U-test).

Results: Myxoid and sclerotic subgroups exposed lower marker expression. In case of endocarditis, the expression of MMP 1 (2.88 ± 0.33; p = 0.009), MMP 9 (2.77 ± 0.44; p = 0.005), and TIMP 1 (2.33 ± 0.86; p = 0.001) were increased to degenerative valve alterations (MMP 1—1.71 ± 0.61; MMP 9—1.78 ± 0.70; TIMP1—0.57 ± 0.85). Markers’ expression varies with the progression of the MI disease.

Conclusion: Apoptosis of endocardial valve cells, the degradation of elastin, and increased collagen synthesis by MMPs may play a key role in valve remodeling and degeneration. The results show that MMP 1 and MMP 9, and TIMP 1 participate in valve disease. MMP 9 appears an indicator for progression of the disease. The lack of mitral TIMP 2 expression is suggested to be associated with the severity of the patients’ health conditions indicated for mitral valve surgery as previously found by other studies.