title: Matrix metalloproteinase expression in the ascending aorta and aortic valve.
abstract: Extracellular matrix degradation and increased proteolytic enzyme (matrix metalloproteinase (MMP)) activity characterise abdominal aortic aneurysm formation. Post-stenotic dilatation of ascending aorta is associated with aortic stenosis and regurgitation, haemodynamically normal bicuspid aortic valve (BAV) and following AV replacement. We aimed to determine an association between ascending aortic pathology and abnormal AV, with particular reference to MMPs, and ascertain differences between BAV and tricuspid (TAV) AV. Subset of the study population (n=19) with a preoperative ascending aorta of >4 cm was analysed. Samples of ascending aorta and AV were obtained from 82 patients (TAV, n=54, BAV, n=28) undergoing surgery. Gene expression of MMP-1, -2, -9 and tissue inhibitor of metalloproteinase (TIMP)-1 and -2 was quantified by real-time RT-PCR. No significant difference was seen in gene expression level of MMPs, TIMPs and ratio of MMPs/TIMPs in ascending aorta and AV between patients with BAV and TAV. MMP-2/TIMP-1 in ascending aorta was greater in BAV, in the subset of patients with preoperative aortic dilatation (P<0.05). No difference exists in gene expression of MMPs in ascending aorta and AV between patients with BAV and TAV. However, patients with larger aortic diameters have increased MMP-2/TIMP-1. Modifying MMP expression may have a role in development of aneurysms.
authors.affiliation: Department of Cardiac Surgery and Cardiac and Vascular Sciences, St. George's Hospital, University of London, London, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Wilton
authors.forename: Martin
authors.initials: M
authors.lastname: Bland
authors.forename: Matthew
authors.initials: M
authors.lastname: Thompson
authors.forename: Marjan
authors.initials: M
authors.lastname: Jahangiri
mesh_terms: D000368:Aged; D001013:Aorta, Thoracic / Q000201:enzymology*; D017545:Aortic Aneurysm, Thoracic / Q000201:enzymology* / Q000503:physiopathology / Q000601:surgery; D019917:Blood Vessel Prosthesis Implantation / Q000379:methods; D018450:Disease Progression; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006349:Heart Valve Diseases / Q000201:enzymology* / Q000503:physiopathology / Q000601:surgery; D019918:Heart Valve Prosthesis Implantation / Q000379:methods; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D008943:Mitral Valve / Q000201:enzymology*; D011379:Prognosis; D011446:Prospective Studies; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D012313:RNA; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1