Matrix Metalloproteinase-2 Inhibition in Acute Ischemia-Reperfusion Heart Injury—Cardioprotective Properties of Carvedilol

Skrzypiec-Spring, Monika; Urbaniak, Joanna; Sapa-Wojciechowska, Agnieszka; Orda, Alina; Karolko, Bożena; Danielewicz, Regina; Bil‐Lula, Iwona; Woźniak, Mieczysław; Schulz, Richard; Szeląg, Adam

doi:10.3390/ph14121276

Cited by 10 publications

(7 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MMP-2 also cleaves and activates GSK-3

in the cytosol, which may contribute to cardiac damage [ 125 ]. Consequently, inhibiting intracellular MMP-2 activities in hearts during ischemia/reperfusion was found to exert cardioprotective effects [ 126 , 127 ]. It is worth mentioning that TIMP-4 was also found within thin myofilaments inside cardiomyocytes, which indicates a potential regulatory role of TIMPs inside cells [ 128 ].…”

Section: Novel Role In Cardiac Dysfunctionmentioning

confidence: 99%

Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu

Maybee

Ink

Ali

2022

IJMS

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) are critical enzymes involved in a variety of cellular processes. MMPs are well known for their ability to degrade the extracellular matrix (ECM) and their extracellular role in cell migration. Recently, more research has been conducted on investigating novel subcellular localizations of MMPs and their intracellular roles at their respective locations. In this review article, we focus on the subcellular localization and novel intracellular roles of two closely related MMPs: membrane-type-1 matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase-2 (MMP-2). Although MT1-MMP is commonly known to localize on the cell surface, the protease also localizes to the cytoplasm, caveolae, Golgi, cytoskeleton, centrosome, and nucleus. At these subcellular locations, MT1-MMP functions in cell migration, macrophage metabolism, invadopodia development, spindle formation and gene expression, respectively. Similar to MT1-MMP, MMP-2 localizes to the caveolae, mitochondria, cytoskeleton, nucleus and nucleolus and functions in calcium regulation, contractile dysfunction, gene expression and ribosomal RNA transcription. Our particular interest lies in the roles MMP-2 and MT1-MMP serve within the nucleus, as they may provide critical insights into cancer epigenetics and tumor migration and invasion. We suggest that targeting nuclear MT1-MMP or MMP-2 to reduce or halt cell proliferation and migration may lead to the development of new therapies for cancer and other diseases.

show abstract

“…MMP-2 also cleaves and activates GSK-3

Section: Novel Role In Cardiac Dysfunctionmentioning

confidence: 99%

Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu

Maybee

Ink

Ali

2022

IJMS

View full text Add to dashboard Cite

show abstract

Section: Use Of Nonspecific and Specific Inhibitors For Mmp-2 In Hfmentioning

confidence: 99%

“…Drugs used in the treatment of hypertension, such as verapamil, carvedilol and trimetazidine, have shown positive effects on cardiac function and remodeling associated with decreased activity and expression of MMP-2 [ 107 , 108 , 109 ]. Low-dose carvedilol is cardioprotective and inhibits MMP-2 activity in an ischemia/reperfusion model [ 109 ]. Verapamil has been shown to reduce MMP-2 activity by decreasing oxidative stress and calpain-1 that regulates MMP-2 activity in a model of HF induced by hypertension [ 108 ].…”

Section: Use Of Nonspecific and Specific Inhibitors For Mmp-2 In Hfmentioning

confidence: 99%

Matrix Metalloproteinase 2 as a Pharmacological Target in Heart Failure

et al. 2022

View full text Add to dashboard Cite

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.

show abstract

“…MMP-2 also cleaves and activates GSK-3 in the cytosol which may contribute to cardiac damage [1]. Consequently, inhibiting intracellular MMP-2 activities in hearts during ischemia/reperfusion was found to exert cardioprotective effects [82,83]. It is worth mentioning that TIMP-4 was also found within thin myofilaments inside cardiomyocytes which indicate a potential regulatory role of TIMPs inside cells [84].…”

Section: Novel Roles Of Mmp-2 Inside Cellsmentioning

confidence: 99%

Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu

Maybee¹,

Ink²,

Ali³

2022

Preprint

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) are critical enzymes involved in a variety of cellular processes. MMPs are well known for their ability to degrade the extracellular matrix (ECM) and their extracellular role in cell migration. Recently, more research has been conducted on investigating novel subcellular localizations of MMPs and their intracellular roles at the respective locations. In this review article, we focus on the subcellular localization and novel intracellular roles of two MMPs closely related: membrane-type-1 matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase-2 (MMP-2). Although MT1-MMP is commonly known to localize on the cell surface, the protease also localizes to the cytoplasm, caveolae, Golgi, cytoskeleton, centrosome, and nucleus. At these subcellular locations, MT1-MMP functions in cell migration, macrophage metabolism, invadopodia development, spindle formation and genes expression, respectively. Similar to MT1-MMP, MMP-2 localizes to the caveolae, mitochondria, cytoskeleton, nucleus and nucleolus, and functions in calcium regulation, contractile dysfunction, genes expression and ribosomal RNA transcription. Our particular interest lies in the role MMP-2 and MT1-MMP serve within the nucleus, as it may provide critical insights into cancer epigenetics and tumor migration and invasion. We suggest that targeting nuclear MT1-MMP or MMP-2 to reduce or halt cell proliferation and migration may lead to the development of new therapies in cancer and other diseases.

show abstract

Matrix Metalloproteinase-2 Inhibition in Acute Ischemia-Reperfusion Heart Injury—Cardioprotective Properties of Carvedilol

Cited by 10 publications

References 31 publications

Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu

Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu

Matrix Metalloproteinase 2 as a Pharmacological Target in Heart Failure

Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu

Contact Info

Product

Resources

About