AIMS: Aortic valve diseases are characterized by pathological remodelling of valvular tissue but the cellular and molecular effectors involved in these processes are not well known. The role of matrix metalloproteinase (MMP)-2, MMP-9, MMP-3, MMP-7, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 are investigated here. METHODS AND RESULTS: Histological analysis of pathological valves [aortic stenosis (AS) (n=49), aortic regurgitation (AR) (n=23)] and control valves (n=8) was performed. The main tissue abnormalities (calcification, inflammatory cells, and capillaries) observed in AS were less severe or absent in AR. However, both groups of pathological valves displayed similar histological signs of extracellular matrix (ECM) remodelling. Biochemical analysis of MMPs and TIMPs (gelatin and casein zymography and ELISA) was performed on valve extracts. MMP-2 activity was not significantly different in control and pathological valves. Increases in MMP-9 and MMP-3 in AS demonstrated an inflammatory state. Finally, there was a four- to seven-fold increase of TIMP-1 in pathological valves. TIMP-1, TIMP-2, and MMP-2 were synthesized by the valvular interstitial cells in primary culture. CONCLUSION: This study demonstrates the involvement of the MMP/TIMP system in ECM remodelling of both AS and AR. These findings provide evidence of inflammatory injury more severe in AS than in AR and involvement of mesenchymal cell response.
AIMS: Aortic valve diseases are characterized by pathological remodelling of valvular tissue but the cellular and molecular effectors involved in these processes are not well known. The role of matrix metalloproteinase (MMP)-2, MMP-9, MMP-3, MMP-7, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 are investigated here. METHODS AND RESULTS: Histological analysis of pathological valves [aortic stenosis (AS) (n=49), aortic regurgitation (AR) (n=23)] and control valves (n=8) was performed. The main tissue abnormalities (calcification, inflammatory cells, and capillaries) observed in AS were less severe or absent in AR. However, both groups of pathological valves displayed similar histological signs of extracellular matrix (ECM) remodelling. Biochemical analysis of MMPs and TIMPs (gelatin and casein zymography and ELISA) was performed on valve extracts. MMP-2 activity was not significantly different in control and pathological valves. Increases in MMP-9 and MMP-3 in AS demonstrated an inflammatory state. Finally, there was a four- to seven-fold increase of TIMP-1 in pathological valves. TIMP-1, TIMP-2, and MMP-2 were synthesized by the valvular interstitial cells in primary culture. CONCLUSION: This study demonstrates the involvement of the MMP/TIMP system in ECM remodelling of both AS and AR. These findings provide evidence of inflammatory injury more severe in AS than in AR and involvement of mesenchymal cell response.
Authors: Jae-Joon Jung; Mahmoud Razavian; Azariyas A Challa; Lei Nie; Reza Golestani; Jiasheng Zhang; Yunpeng Ye; Kerry S Russell; Simon P Robinson; Donald D Heistad; Mehran M Sadeghi Journal: J Nucl Med Date: 2015-04-23 Impact factor: 10.057
Authors: Donal MacGrogan; Guillermo Luxán; Anita Driessen-Mol; Carlijn Bouten; Frank Baaijens; José Luis de la Pompa Journal: Cold Spring Harb Perspect Med Date: 2014-11-03 Impact factor: 6.915
Authors: Vishal Patel; Katrina Carrion; Andrew Hollands; Andrew Hinton; Thomas Gallegos; Jeffrey Dyo; Roman Sasik; Emma Leire; Gary Hardiman; Salah A Mohamed; Sanjay Nigam; Charles C King; Victor Nizet; Vishal Nigam Journal: FASEB J Date: 2015-01-28 Impact factor: 5.191
Authors: Salma Ayoub; Giovanni Ferrari; Robert C Gorman; Joseph H Gorman; Frederick J Schoen; Michael S Sacks Journal: Compr Physiol Date: 2016-09-15 Impact factor: 9.090