Matrix Metalloproteinase Polymorphisms in Patients with Floppy Mitral Valve/Mitral Valve Prolapse (FMV/MVP) and FMV/MVP Syndrome

Cardiology ◽  
2017 ◽  
Vol 138 (3) ◽  
pp. 179-185 ◽  
Author(s):  
Sarah M. Lima ◽  
Antonios A. Pitsis ◽  
Timotheos G. Kelpis ◽  
Mohamed H. Shahin ◽  
Taimour Y. Langaee ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Matrix Metalloproteinase ◽  
Mitral Valve Prolapse ◽  
Odds Ratio ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Matrix Metalloproteinase 2 ◽  
Nucleotide Polymorphisms ◽  
Collagen Turnover ◽  
Single Nucleotide

Background: It has been suggested that collagen abnormalities of the mitral valve are present in patients with floppy mitral valve (FMV)/mitral valve prolapse (MVP). Genetic factors determining collagen synthesis and degradation have not been well defined in these patients. This study was undertaken to determine whether selective polymorphisms of matrix metalloproteinase-2 (MMP2) or transforming growth factor-β (TGFβ), with known or putative effects on collagen turnover, are more frequent in FMV/MVP. Methods: Single nucleotide polymorphisms (SNPs) in select genes related to collagen turnover, including MMP2 rs2285053, MMP2 rs243865, TGFβ1 rs1800469, and TGFβ2 rs900, were determined in 98 patients with FMV/MVP who had severe mitral regurgitation and compared to 99 controls. Results:MMP2 rs243865 was the only SNP significantly associated with FMV/MVP as compared to the control (odds ratio 2.07, 95% CI 1.23-3.50, p = 0.006). MMP2 rs228503 was the only SNP significantly associated with the FMV/MVP syndrome as compared to patients with FMV/MVP without the syndrome (odds ratio 2.41, 95% CI 1.08-5.40, p = 0.032). Conclusion: The frequency of certain MMP2 polymorphisms is higher in patients with the FMV/MVP syndrome and patients with FMV/MVP without the syndrome. The data suggest that a genetic predisposition that alters collagen turnover may play a role in the pathogenesis and development of FMV/MVP.

scholarly journals Cardiomyopathy in young adults with classic mitral valve prolapse

2013 ◽  
Vol 24 (4) ◽  
pp. 694-701 ◽  
Author(s):  
Eduard Malev ◽  
Svetlana Reeva ◽  
Lyubov Vasina ◽  
Eugeny Timofeev ◽  
Asiyet Pshepiy ◽  
...  
Keyword(s):  
Young Adults ◽  
Growth Factor ◽  
Mitral Valve ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Mitral Valve Prolapse ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Left Ventricular ◽  
Control Group

AbstractBackground: In some inherited connective tissue diseases with involvement of the cardiovascular system, for example, Marfan syndrome, early impairment of left ventricular function, which have been described as Marfan-related cardiomyopathy has been reported. Our aim was to evaluate the left ventricular function in young adults with mitral valve prolapse without significant mitral regurgitation using two-dimensional strain imaging and to determine the possible role of the transforming growth factor-β pathway in its deterioration. Methods: We studied 78 young adults with mitral valve prolapse without mitral regurgitation in comparison with 80 sex-matched and age-matched healthy individuals. Longitudinal strain and strain rates were defined using spackle tracking. Concentrations of transforming growth factor-β1 and β2 in serum were determined by enzyme-linked immunosorbent assays. Results: In 29 patients, classic relapse was identified with a leaflet thickness of ≥ 5 mm; 49 patients had a non-classic mitral valve prolapse. Despite the similar global systolic function, a significant reduction in global strain was found in the classic group (−15.5 ± 2.9%) compared with the non-classic group (−18.7 ± 3.8; p = 0.0002) and the control group (−19.6 ± 3.4%; p < 0.0001). In young adults with non-classic prolapse, a reduction in longitudinal deformation was detected only in septal segments. Transforming growth factor-β1 and β2 serum levels were elevated in patients with classic prolapse as compared with the control group and the non-classic mitral valve prolapse group. Conclusions: These changes in the deformations may be the first signs of deterioration of the left ventricular function and the existence of primary cardiomyopathy in young adults with mitral valve prolapse, which may be caused by increased transforming growth factor-β signalling.

High Glucose Decreases Matrix Metalloproteinase-2 Activity in Rat Mesangial Cells via Transforming Growth Factor-β1

2001 ◽  
Vol 9 (4) ◽  
pp. 249-257 ◽  
Author(s):  
Rekha Singh ◽  
Ruo Hua Song ◽  
Nahid Alavi ◽  
Alfredo A. Pegoraro ◽  
Ashok K. Singh ◽  
...  
Keyword(s):  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Transforming Growth Factor Β ◽  
Matrix Metalloproteinase 2

The Control of Matrix Metalloproteinase-2 Expression in Normal and Keratoconic Corneal Keratocyte Cultures

2000 ◽  
Vol 10 (4) ◽  
pp. 276-285 ◽  
Author(s):  
B.T. Parkin ◽  
V.A. Smith ◽  
D.L. Easty
Keyword(s):  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Early Phase ◽  
Transforming Growth Factor ◽  
Polyacrylamide Gel Electrophoresis ◽  
Transforming Growth Factor Β ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Dot Blot ◽  
Corneal Keratocytes

Purpose Early phase keratoconic comeas and their cultured keratocytes abnormally produce the Mr 62,000 form of the matrix metalloproteinase-2 (MMP-2). It is known that platelet derived growth factor (PDGF) and transforming growth factor-β (TGF-β) are involved in the regulation of MMP activity and tissue inhibitor of metalloproteinase (TIMP) production in non-ocular tissues. The purpose of this enquiry was to determine whether these growth factors also play a role in the activity and/or production of corneal MMP-2 and TIMP, and whether their activity could account for the existence of the Mr 62,000 form of MMP-2 in keratoconic corneas. Methods Confluent cultures of normal and early-phase keratoconic corneal keratocytes were established and incubated in serum-free media in the presence or absence of PDGF and TGF-β. The proteins secreted by these cells over periods of 7 days were harvested for analysis. The total protein produced was determined spectrophotometrically. MMP-2 was visualised by SDS-gelatin polyacrylamide gel electrophoresis and assayed using radiolabelled type IV collagen as substrate. The enzyme inhibitors, TIMP-1 and TIMP-2, were quantified by dot blot immunoassay. Results The addition of PDGF or TGF-β to the culture medium of keratoconic corneal keratocytes had no significant effect on overall protein production, MMP-2 activity or on the amounts of TIMP-1 and TIMP-2 secreted. These observations also applied to normal corneal keratocytes, with the exception that PDGF induced expression of the Mr 62,000 species of MMP-2. Conclusions PDGF may be involved in the production of the Mr 62,000 species of MMP-2 that is abnormally produced by early-phase keratoconic corneal keratocytes.

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