Elevated MMP9 expression contributes to extracellular matrix degradation, activates a proteinase-activated receptor-1 signaling cascade, and contributes to cardiomyocyte dysfunction and heart failure in single ventricle cases [422]; MMP2, MMP9, MMP14 variants associated with unicommissural aortic valves characterized by congenital fusion of adjacent cusps of two commissures [419]; MMP9 variants associated with ascending aortic aneurysm, thoracic aortic dissection [423] and aortic stenosis [424] (human). This evidence concerns the gene F2R and heart failure.