Profile and localization of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in human heart valves.
OBJECTIVE
Tissue turnover is one of many factors involved in the operational longevity of heart valves. An understanding of how valves remodel their matrix in response to the hemodynamic environment in health and disease is crucial to the design and biological responsiveness of tissue-engineered valve substitutes. Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in matrix remodeling in several tissues, and include interstitial collagenase (MMP-1, MMP-13), the gelatinases (MMP-2, MMP-9) and stromelysin (MMP-3).


METHODS
Expression of MMPs and their tissue inhibitors (TIMPs) in human aortic, mitral, tricuspid and pulmonary valves from unused donor or transplant recipient hearts was determined by immunohistochemical staining using antibodies against human MMP-1, MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1, TIMP-2, TIMP-3. Cell identification was achieved using antibodies against CD31(endothelial cells), smooth muscle alpha-actin (microfilaments) and CD68 (macrophages).


RESULTS
MMP-1 was expressed in all valves, whereas MMP-2 was only expressed in aortic and pulmonary leaflets. MMP-3 and MMP-9 were not expressed. TIMP-1 and TIMP-2 were expressed in all leaflets, whereas TIMP-3 was observed only in tricuspid leaflets.


CONCLUSIONS
Valves have a specific pattern of expression of MMPs and TIMPs, which appears to vary in different heart valves. The functional implications and central mechanisms responsible require further study. These findings have important implications in understanding the dynamic nature of valve remodeling and in aiding the development of tissue-engineered valves.
Dreger
Sally A
SA
Division of Cardiothoracic Surgery, National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology and Medicine at Harefield Hospital, Heart Science Centre, UK.
Taylor
Patricia M
PM
Allen
Sean P
SP
Yacoub
Magdi H
MH
D000199:Actins / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001021:Aortic Valve / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D008875:Middle Aged; D008943:Mitral Valve / Q000378:metabolism; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011664:Pulmonary Valve / Q000378:metabolism; D012016:Reference Values; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis*; D014261:Tricuspid Valve / Q000378:metabolism; D000097382:CD68 Molecule
D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D020782:Matrix Metalloproteinases; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019714:Tissue Inhibitor of Metalloproteinases; C067980:CD68 antigen, human; D000097382:CD68 Molecule