Regulation of matrix metalloproteinases and their inhibitors in the left ventricular myocardium of patients with aortic stenosis

Fielitz, Jens; Leuschner, Manuela; Zurbrügg, H. R.; Hannack, Britta; Pregla, Reinhard; Hetzer, Roland; Regitz‐Zagrosek, Vera

doi:10.1007/s00109-004-0606-4

Cited by 68 publications

(50 citation statements)

References 49 publications

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“…This finding suggests that the cell therapy has no effect on the mechanisms of inflammation or else, other sources of hyperproduction of these substances are not affected by the utilized technique. It is interesting to register, however, that MMP-2 levels increased after BMCT, which might correlate with increased collagen turnover 36,37 .…”

Section: Bnp (Pg/ml)mentioning

confidence: 98%

Transplante de células da medula óssea na insuficiência cardíaca chagásica: relato da primeira experiência humana

Vilas-Boas¹,

Feitosa²,

Soares³

et al. 2011

Arq. Bras. Cardiol.

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Section: Bnp (Pg/ml)mentioning

confidence: 98%

Transplante de células da medula óssea na insuficiência cardíaca chagásica: relato da primeira experiência humana

Vilas-Boas¹,

Feitosa²,

Soares³

et al. 2011

Arq. Bras. Cardiol.

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“…85 For instance, pressure overload is associated with increased levels of TIMPs during the compensated phase, whereas a relative increase in MMPs is observed in parallel with the development of LV systolic dysfunction. [86][87][88] The family of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) proteinases is another group of extracellular metalloproteinases with roles in ECM degradation. 89 Their ability to cleave procollagens and proteoglycans 89,90 suggests that they may influence on cardiac ECM integrity and function during heart failure progression.…”

Section: Fibrosismentioning

confidence: 99%

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

et al. 2013

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Sustained pressure overload induces heart failure, the main cause of mortality in the Western world. Increased understanding of the underlying molecular mechanisms is essential to improve heart failure treatment. Despite important functions in other tissues, cardiac proteoglycans have received little attention. Syndecan‐4, a transmembrane heparan sulfate proteoglycan, is essential for pathological remodeling, and we here investigated its expression and shedding during heart failure. Pressure overload induced by aortic banding for 24 h and 1 week in mice increased syndecan‐4 mRNA, which correlated with mRNA of inflammatory cytokines. In cardiac myocytes and fibroblasts, tumor necrosis factor‐α, interleukin‐1β and lipopolysaccharide through the toll‐like receptor‐4, induced syndecan‐4 mRNA. Bioinformatical and mutational analyses in HEK293 cells identified a functional site for the proinflammatory nuclear factor‐κB transcription factor in the syndecan‐4 promoter, and nuclear factor‐κB regulated syndecan‐4 mRNA in cardiac cells. Interestingly, tumor necrosis factor‐α, interleukin‐1β and lipopolysaccharide induced nuclear factor‐κB‐dependent shedding of the syndecan‐4 ectodomain from cardiac cells. Overexpression of syndecan‐4 with mutated enzyme‐interacting domains suggested enzyme‐dependent heparan sulfate chains to regulate shedding. In cardiac fibroblasts, lipopolysaccharide reduced focal adhesion assembly, shown by immunohistochemistry, suggesting that inflammation‐induced shedding affects function. After aortic banding, a time‐dependent cardiac recruitment of T lymphocytes was observed by measuring CD3, CD4 and CD8 mRNA, which was reduced in syndecan‐4 knockout hearts. Finally, syndecan‐4 mRNA and shedding were upregulated in failing human hearts. Conclusively, our data suggest that syndecan‐4 plays an important role in the immune response of the heart to increased pressure, influencing cardiac remodeling and failure progression.

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“…Several MMPs are upregulated in cardiac hypertrophy and an imbalance between MMPs and their endogenous inhibitors (tissue inhibitor of metalloproteinases-TIMPs) may underlie the transition of compensated LVH to dilated LVH. [3][4][5][6][7] In addition, experimental evidence suggests that nonspecific inhibition of MMPs, especially MMP-2, ameliorates hypertensive cardiovascular remodelling. 8 MMPs activities are regulated at different levels including transcription, activation of latent forms of MMPs and inhibition by TIMPs 5,9 In this respect, genetic polymorphisms in MMP-2 gene may also affect MMP-2 expression or activity, as shown in several disease conditions.…”

Section: Introductionmentioning

confidence: 99%

Common matrix metalloproteinase 2 gene haplotypes may modulate left ventricular remodelling in hypertensive patients

et al. 2011

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Matrix metalloproteinases (MMPs) are involved in cardiac remodelling. We examined whether MMP-2 genetic polymorphisms are associated with hypertension and left ventricular (LV) remodelling in hypertensive patients. We studied 160 hypertensive patients and 123 healthy controls. Echocardiography was performed in all patients and the C À1306 T (rs243865) and C À735 T (rs 2285053) MMP-2 polymorphisms were analysed. Haplo.stats analysis was used to evaluate whether MMP-2 haplotypes are associated with hypertension and with extremes in LV mass index (LVMI). Multiple linear regression analysis was performed to assess whether MMP-2 genotypes or haplotypes affect LVMI and other echocardiography parameters. The C À1306 T 'CC' genotype was associated with reduced LVMI and LV end-diastolic diameter (EDD) (P ¼ 0.0365 and P ¼ 0.0438, respectively). The haplotype 'C, C' was associated with reduced LVMI and EDD (P ¼ 0.0278 and P ¼ 0.0322, respectively). The comparison of upper and lower extremes of the LVMI phenotype showed that the 'C, C' haplotype was more common in the lower LVMI group (P ¼ 0.0060), whereas the 'T, C' haplotype was more common in the higher quartile of LVMI (P ¼ 0.0187), and this haplotype was associated with increased risk of higher LVMI values (odds ratio ¼ 3.5121, 95% confidence interval ¼ 1.3193-9.3494). The findings suggest that MMP-2 polymorphisms affect hypertension-induced LV remodelling.

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Regulation of matrix metalloproteinases and their inhibitors in the left ventricular myocardium of patients with aortic stenosis

Cited by 68 publications

References 49 publications

Transplante de células da medula óssea na insuficiência cardíaca chagásica: relato da primeira experiência humana

Transplante de células da medula óssea na insuficiência cardíaca chagásica: relato da primeira experiência humana

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

Common matrix metalloproteinase 2 gene haplotypes may modulate left ventricular remodelling in hypertensive patients

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