Heart Remodelation: Role of MMPs

Pytliak, Marek; Vaník, Viliam; Bojčík, Peter

doi:10.5772/intechopen.71662

Cited by 4 publications

(4 citation statements)

References 69 publications

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“…In addition, fibroblasts surround cardiomyocytes, and the myocyte function depends on the fibroblast. In pathological processes, cytokines and growth factors alter the fibroblast phenotype by increasing the secretion of ECM proteins that lead to fibrosis [ 25 , 26 , 27 ]. Fibroblasts and myofibroblasts are the central MMP-secreting cells in the heart and are indicated as a therapeutic target for the treatment of myocardial infarction, hypertension and HF [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinase 2 as a Pharmacological Target in Heart Failure

et al. 2022

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Heart failure (HF) is an acute or chronic clinical syndrome that results in a decrease in cardiac output and an increase in intracardiac pressure at rest or upon exertion. The pathophysiology of HF is heterogeneous and results from an initial harmful event in the heart that promotes neurohormonal changes such as autonomic dysfunction and activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, and inflammation. Cardiac remodeling occurs, which is associated with degradation and disorganized synthesis of extracellular matrix (ECM) components that are controlled by ECM metalloproteinases (MMPs). MMP-2 is part of this group of proteases, which are classified as gelatinases and are constituents of the heart. MMP-2 is considered a biomarker of patients with HF with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). The role of MMP-2 in the development of cardiac injury and dysfunction has clearly been demonstrated in animal models of cardiac ischemia, transgenic models that overexpress MMP-2, and knockout models for this protease. New research to minimize cardiac structural and functional alterations using non-selective and selective inhibitors for MMP-2 demonstrates that this protease could be used as a possible pharmacological target in the treatment of HF.

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Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinase 2 as a Pharmacological Target in Heart Failure

et al. 2022

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“…From the numerous MMPs characterized and identified, gelatinases (MMP-2 and MMP-9) play a role in remodeling of the cardiac infrastructure. They have been reported to play a role in inflammation-induced imbalance of extracellular matrix turnover in the heart ( Pytliak et al, 2017 ). It has been demonstrated that non-toxic cadmium stimulates MMP-9 and MMP-2 expression in the cardiovascular system inducing vascular inflammation and promoting atherosclerosis ( Knoflach et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Chronic Cadmium Exposure Alters Cardiac Matrix Metalloproteinases in the Heart of Sprague-Dawley Rat

et al. 2021

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The aim of this study was to evaluate the role of chronic cadmium exposure in modulating cardiac matrix metalloproteinases (MMPs) in the heart of rats. Adult male Sprague-Dawley rats were exposed to 15 ppm CdCl2 in drinking water for 10 weeks followed by withdrawal of cadmium treatment for 4 weeks. Following the completion of the treatment, gene expression of inflammatory mediators (IL-1β, IL-6, IL-10, TNF-α and NF-κB), protein expression of MMP-2, MMP-9 and their respective inhibitors- TIMP-1 and TIMP-2, and gelatinolytic activity of MMP-2 and MMP-9 were determined. At the protein level, cadmium incites a differential effect on the expression and activity of gelatinases and their endogenous inhibitors in an exposure-dependent manner. Results also show that the administered cadmium dose elicits an inflammatory response until week 10 that slightly diminishes after 4 weeks. This study provides evidence of cadmium-induced imbalance in the MMP-TIMP system in the cardiac tissue. This imbalance may be mediated by cadmium-induced inflammation that could contribute to various cardiovascular pathologies.

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“…The diversified evolution of cardiac damage mediated by ROS further emerges through the demonstration that their concentration can also variously modulate the action of the different isoforms of MMP-2. Particularly, it has been proved that, in the setting of an acute redox injury, a considerable part of newly synthesized MMP-2 is activated, thus remaining within the cell associated with the sarcomeric proteins and determining the cleavage of several crucial components of the contractile apparatus [ 11 , 45 ]. On the other hand, under persistent oxidative stress and the subsequent activation of an alternative intronic promoter, the expression of the NT-MMP-2 isoform occurs, promoting the following: the induction of specific mitochondrial-nuclear stress signaling, the impairment of cardiomyocyte function, and finally ventricular hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats

Gliozzi

Scarano

Musolino

et al. 2020

IJMS

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Clinical management of diabetic cardiomyopathy represents an unmet need owing to insufficient knowledge about the molecular mechanisms underlying the dysfunctional heart. The aim of this work is to better clarify the role of matrix metalloproteinase 2 (MMP-2) isoforms and of translocator protein (TSPO)/voltage-dependent anion-selective channel 1 (VDAC1) modulation in the development of hyperglycaemia-induced myocardial injury. Hyperglycaemia was induced in Sprague-Dawley rats through a streptozocin injection (35 mg/Kg, i.p.). After 60 days, cardiac function was analysed by echocardiography. Nicotinamide Adenine Dinucleotide Phosphate NADPH oxidase and TSPO expression was assessed by immunohistochemistry. MMP-2 activity was detected by zymography. Superoxide anion production was estimated by MitoSOX™ staining. Voltage-dependent anion-selective channel 1 (VDAC-1), B-cell lymphoma 2 (Bcl-2), and cytochrome C expression was assessed by Western blot. Hyperglycaemic rats displayed cardiac dysfunction; this response was characterized by an overexpression of NADPH oxidase, accompanied by an increase of superoxide anion production. Under hyperglycaemia, increased expression of TSPO and VDAC1 was detected. MMP-2 downregulated activity occurred under hyperglycemia and this profile of activation was accompanied by the translocation of intracellular N-terminal truncated isoform of MMP-2 (NT-MMP-2) from mitochondria-associated membrane (MAM) into mitochondria. In the onset of diabetic cardiomyopathy, mitochondrial impairment in cardiomyocytes is characterized by the dysregulation of the different MMP-2 isoforms. This can imply the generation of a “frail” myocardial tissue unable to adapt itself to stress.

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Heart Remodelation: Role of MMPs

Cited by 4 publications

References 69 publications

Matrix Metalloproteinase 2 as a Pharmacological Target in Heart Failure

Matrix Metalloproteinase 2 as a Pharmacological Target in Heart Failure

Chronic Cadmium Exposure Alters Cardiac Matrix Metalloproteinases in the Heart of Sprague-Dawley Rat

Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats

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