title: Role of matrix metalloproteinases and their tissue inhibitor of metalloproteinases in myxomatous change of cardiac floppy valves.
abstract: To clarify the underlying cause of myxomatous changes in cardiac floppy valves, the expression of the matrix metalloproteinases (MMP) and the tissue inhibitors of metalloproteinases (TIMP) was investigated in cardiac valves. Valves were obtained from nine patients with floppy valves, from 13 patients with other valvular disease types, and from four patients with normal valves. Immunohistochemical analyses for MMP-2, MMP-9, TIMP-1, and TIMP-2, and gelatin zymography for MMP-2 and MMP-9 were performed. Compared with the spongiosa of normal valves, the myxomatous area of floppy valves had stronger immunohistochemical reaction to MMP-2 and MMP-9, and weaker reaction to TIMP-2. Activated MMP-2 and MMP-9 were detected in eight out of nine cases of floppy valves. Activated MMP-2 was detected at low levels in two cases of normal valves showing mild expansion of the spongiosa without macroscopic floppiness. The ratio of active/total MMP-2 and MMP-9 increased in floppy valves compared with normal valves. These results suggest that the imbalance between MMP and TIMP and the increased activity of MMP-2 and MMP-9 may correlate with myxomatous changes observed in floppy valves. Valves with a slight myxomatous change and activated MMP-2 may develop into floppy valves with increases in the activity of MMP.
authors.affiliation: Department of Analytic Human Pathology, Nippon Medical School, and Division of Surgical Pathology, Nippon Medical School Hospital, Tokyo, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Togashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Tamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Nitta
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ishizaki
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugisaki
authors.forename: Yuh
authors.initials: Y
authors.lastname: Fukuda
mesh_terms: D000368:Aged; D018450:Disease Progression; D005260:Female; D006338:Heart Neoplasms / Q000378:metabolism / Q000473:pathology*; D006351:Heart Valves / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D009232:Myxoma / Q000378:metabolism / Q000473:pathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism* / Q000502:physiology
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9