Matrix Metalloproteinases MMP-1 and MMP-9 and Their Inhibitor TIMP-1 as Markers of Dilated Cardiomyopathy in Patients of Different Age

Аntonov, I. B.; Козлов, К Л; Paltseva, E. M.; Polyakova, O. V.; Linkova, N. S.

doi:10.1007/s10517-018-4030-0

Cited by 15 publications

(14 citation statements)

References 9 publications

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“…Mmp9 deletion may attenuate age-related myocardial fibrosis and diastolic dysfunction [49]. Circulating MMP-9 has also been shown to be an effective marker of heart failture and dilated cardiomyopathy [42,50]. Therefore, higher expression of mmp9 in adcy9 morphant zebrafish observed in our study may be involved the impairment of extracellular matrix, and cause cardiac abnormalities in zebrafish.…”

Section: Mmp9 In Cardiac Abnormalities In Adcy9 Morphant Zebrafishmentioning

confidence: 58%

Role of the ADCY9 gene in cardiac abnormalities of the Rubinstein-Taybi syndrome

Xia

et al. 2020

Orphanet J Rare Dis

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Background: Rubinstein-Taybi syndrome (RTS) is a rare, congenital, plurimalformative, and neurodevelopmental disorder. Previous studies have reported that large deletions contribute to more severe RTS phenotypes than those caused by CREBBP point mutations, suggesting a concurrent pathogenetic role of flanking genes, typical of contiguous gene syndromes, but the detailed genetics are unclear. Results: This study presented a rare case of Rubinstein-Taybi (RT) syndrome with serious cardiac abnormalities. Based on the clinical and genetic analysis of the patient, the ADCY9 gene deletion was highlighted as a plausible explanation of cardiac abnormalities. In adcy9 morphant zebrafish, cardiac malformation was observed. Immunofluorescence study disclosed increased macrophage migration and cardiac apoptosis. RNA sequencing in zebrafish model highlighted the changes of a number of genes, including increased expression of the mmp9 gene which encodes a matrix metalloproteinase with the main function to degrade and remodel extracellular matrix. Conclusions: In this study, we identified a plausible new candidate gene ADCY9 of CHD through the clinical and genetic analysis of a rare case of Rubinstein-Taybi (RT) syndrome with serious cardiac abnormalities. By functional study of zebrafish, we demonstrated that deletion of adcy9 is the causation for the cardiac abnormalities. Cardiac apoptosis and increased expression of the MMP9 gene are involved in the pathogenesis.

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Section: Mmp9 In Cardiac Abnormalities In Adcy9 Morphant Zebrafishmentioning

confidence: 58%

Role of the ADCY9 gene in cardiac abnormalities of the Rubinstein-Taybi syndrome

Xia

et al. 2020

Orphanet J Rare Dis

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“…Hence, various biomarkers have been investigated in the literature to predict fibrosis. MMPs and their inhibitors (TIMP) are promising candidates for the treatment of patients with HF ( 16 , 17 ). Our study reported that MMP-9 was significantly elevated in HF patients with ischemic cardiomyopathy who had cardiac fibrosis on CMR, and this increase positively correlated with the amount of fibrosis detected by CMR.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Serum Matrix Metalloproteinase and Myocardial Fibrosis Detected with Cardiac MRI in Heart Failure Patients with Reduced Ejection Fraction

Çelik¹

2020

Anatol J Cardiol

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Objective: A strong correlation exists between myocardial fibrosis and heart failure (HF). Myocardial fibrosis can be detected by cardiac magnetic resonance (CMR), which is a crucial noninvasive imaging method with high specificity and sensitivity. Matrix metalloproteinases (MMPs) are primary proteases responsible for the degradation of extracellular matrix (ECM) components, and they play a vital role in maintaining the balance between anabolism and catabolism of ECM. This study aims to investigate the correlation between cardiac fibrosis detected on CMR and serum MMP-9 levels in patients with HF. Methods: We enrolled 53 patients (age: ≥18 years) with left ventricular ejection fraction (LVEF) ≤40%, who received CMR because of various indications. All patients were divided into two groups-with cardiac fibrosis (n=32) and without cardiac fibrosis (n=21)-detected by CMR with late-Gadolinium. Both groups were then compared according to MMP-9 levels. Results: MMP-9 levels were significantly higher in patients with cardiac fibrosis than those without fibrosis (p<0.01). A correlation was determined between the diffusiveness of fibrosis and serum MMP-9 levels. Besides, a statistically significant correlation was determined between MMP-9 measurements and the number of segments with fibrosis (p<0.05). In the group with cardiac fibrosis, LVEF measurements by CMR were significantly lower (p<0.01), with left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) measurements significantly higher (p<0.01), than the other group. Furthermore, we found a statistically significant correlation between MMP-9 levels and LVEDV and LVESV. Conclusion: MMP-9 levels correlate with cardiac remodeling in patients with HF and could be useful in predicting left ventricular fibrosis. In clinical practice, the use of serum MMP-9 could provide early consideration of therapies for structural and functional pathology of the heart in patients with HF.

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“…Both MMPs and TIMPs can directly impact ECM turnover and homeostasis. Alterations in cardiac expression levels of MMPs and TIMPs have been found in patients with different types of heart disease [27], including idiopathic dilated cardiomyopathy [28,29]. While it was initially thought that MMP activity would limit cardiac fibrosis through ECM protein degradation, new insights have shown that MMPs and TIMPs can directly induce ECM deposition and ECM remodeling based on the type of micro-environment [30].…”

Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

Krebber

Dijk

Vernooij

et al. 2020

IJMS

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Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are pivotal regulators of extracellular matrix (ECM) composition and could, due to their dynamic activity, function as prognostic tools for fibrosis and cardiac function in left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF). We conducted a systematic review on experimental animal models of LVDD and HFpEF published in MEDLINE or Embase. Twenty-three studies were included with a total of 36 comparisons that reported established LVDD, quantification of cardiac fibrosis and cardiac MMP or TIMP expression or activity. LVDD/HFpEF models were divided based on underlying pathology: hemodynamic overload (17 comparisons), metabolic alteration (16 comparisons) or ageing (3 comparisons). Meta-analysis showed that echocardiographic parameters were not consistently altered in LVDD/HFpEF with invasive hemodynamic measurements better representing LVDD. Increased myocardial fibrotic area indicated comparable characteristics between hemodynamic and metabolic models. Regarding MMPs and TIMPs; MMP2 and MMP9 activity and protein and TIMP1 protein levels were mainly enhanced in hemodynamic models. In most cases only mRNA was assessed and there were no correlations between cardiac tissue and plasma levels. Female gender, a known risk factor for LVDD and HFpEF, was underrepresented. Novel studies should detail relevant model characteristics and focus on MMP and TIMP protein expression and activity to identify predictive circulating markers in cardiac ECM remodeling.

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Matrix Metalloproteinases MMP-1 and MMP-9 and Their Inhibitor TIMP-1 as Markers of Dilated Cardiomyopathy in Patients of Different Age

Cited by 15 publications

References 9 publications

Role of the ADCY9 gene in cardiac abnormalities of the Rubinstein-Taybi syndrome

Role of the ADCY9 gene in cardiac abnormalities of the Rubinstein-Taybi syndrome

Relationship Between Serum Matrix Metalloproteinase and Myocardial Fibrosis Detected with Cardiac MRI in Heart Failure Patients with Reduced Ejection Fraction

Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

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