Collagen Synthesis Is Upregulated in Mitral Valves Subjected to Altered Stress

Mitral regurgitation (MR) and abnormal ventricular wall motion (AVWM) are two cardiac conditions that may increase mitral valve (MV) stresses. Theoretically, increased stress could induce damaging MV tissue alterations. These alterations may impair the preferred option of repair, and mandate replacement. It is hypothesized that MV collagen synthesis is upregulated in response to MR and AVWM. To test this hypothesis in a pilot study, an ischemic sheep model (n = 8) was employed. Four sheep underwent selective coronary artery ligation to infarct a papillary muscle, which resulted in MR. Two other sheep underwent similar coronary ligation to create AVWM. As controls, two sheep underwent sham surgery (no ligation), Sheep were killed 4 or 8 weeks post operatively and their MVs were sectioned. Sections were stained with an antibody (SP1.D8, University of lowa) to procollagen I (precursor to collagen I). The percent area of procollagen stain present was measured by image analysis (Optimas Corporation) and used as an indicator of collagen synthesis. Procollagen results indicated that MV collagen synthesis was upregulated by a factor of 1.8 in both the MR and AVWM groups versus controls. In addition, results showed greater upregulation in anterior leaflets compared with posterior leaflets in both infarct groups. These results indicate that MV collagen synthesis is upregulated in response to MR and AVWM.