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Chymase Inhibition Prevents Fibronectin And Myofibrillar Loss And Improves Cardiomyocyte Function And Lv Torsion Angle In Dogs With Isolated Mitral Regurgitation., Betty Pat, Yuanwen Chen, Cheryl Killingsworth, James D Gladden, Ke Shi, Junying Zheng, Pamela C Powell, Greg Walcott, Mustafa I Ahmed, Himanshu Gupta, Ravi Desai, Chih-Chang Wei, Naoki Hase, Tsunefumi Kobayashi, Abdelkarim Sabri, Henk Granzier, Thomas Denney, Michael Tillson, A Ray Dillon, Ahsan Husain, Louis J Dell'italia
Chymase Inhibition Prevents Fibronectin And Myofibrillar Loss And Improves Cardiomyocyte Function And Lv Torsion Angle In Dogs With Isolated Mitral Regurgitation., Betty Pat, Yuanwen Chen, Cheryl Killingsworth, James D Gladden, Ke Shi, Junying Zheng, Pamela C Powell, Greg Walcott, Mustafa I Ahmed, Himanshu Gupta, Ravi Desai, Chih-Chang Wei, Naoki Hase, Tsunefumi Kobayashi, Abdelkarim Sabri, Henk Granzier, Thomas Denney, Michael Tillson, A Ray Dillon, Ahsan Husain, Louis J Dell'italia
Ravi V Desai MD
BACKGROUND: The left ventricular (LV) dilatation of isolated mitral regurgitation (MR) is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix. In addition to profibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases and kallikrein and degrades fibronectin. Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR.
METHODS AND RESULTS: We studied dogs with 4 months of untreated MR (MR; n=9) or MR treated with CI (MR+CI; n=8). Cine MRI demonstrated a >40% increase in LV end-diastolic volume in both groups, consistent with …