scholarly journals Matrix metalloproteinase‐2 co‐localizes with titin in cardiac myocytes and contributes to its proteolysis in ischemia‐reperfusion injury

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Mohammad Abdel‐Motaal Ali ◽  
Woo Jung Cho ◽  
Henk Granzier ◽  
Richard Schulz
Keyword(s):  
Matrix Metalloproteinase ◽  
Reperfusion Injury ◽  
Cardiac Myocytes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Matrix Metalloproteinase 2

scholarly journals Cardioprotective Effect of Novel Matrix Metalloproteinase Inhibitors

2020 ◽  
Vol 21 (19) ◽  
pp. 6990
Author(s):  
Kamilla Gömöri ◽  
Tamara Szabados ◽  
Éva Kenyeres ◽  
Judit Pipis ◽  
Imre Földesi ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Positive Control ◽  
Matrix Metalloproteinase 2 ◽  
Area At Risk ◽  
Triphenyltetrazolium Chloride

Background: We recently developed novel matrix metalloproteinase-2 (MMP-2) inhibitor small molecules for cardioprotection against ischemia/reperfusion injury and validated their efficacy in ischemia/reperfusion injury in cardiac myocytes. The aim of the present study was to test our lead compounds for cardioprotection in vivo in a rat model of acute myocardial infarction (AMI) in the presence or absence of hypercholesterolemia, one of the major comorbidities affecting cardioprotection. Methods: Normocholesterolemic adult male Wistar rats were subjected to 30 min of coronary occlusion followed by 120 min of reperfusion to induce AMI. MMP inhibitors (MMPI)-1154 and -1260 at 0.3, 1, and 3 µmol/kg, MMPI-1248 at 1, 3, and 10 µmol/kg were administered at the 25th min of ischemia intravenously. In separate groups, hypercholesterolemia was induced by a 12-week diet (2% cholesterol, 0.25% cholic acid), then the rats were subjected to the same AMI protocol and single doses of the MMPIs that showed the most efficacy in normocholesterolemic animals were tested in the hypercholesterolemic animals. Infarct size/area at risk was assessed at the end of reperfusion in all groups by standard Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining, and myocardial microvascular obstruction (MVO) was determined by thioflavine-S staining. Results: MMPI-1154 at 1 µmol/kg, MMPI-1260 at 3 µmol/kg and ischemic preconditioning (IPC) as the positive control reduced infarct size significantly; however, this effect was not seen in hypercholesterolemic animals. MVO in hypercholesterolemic animals decreased by IPC only. Conclusions: This is the first demonstration that MMPI-1154 and MMPI-1260 showed a dose-dependent infarct size reduction in an in vivo rat AMI model; however, single doses that showed the most efficacy in normocholesterolemic animals were abolished by hypercholesterolemia. The further development of these promising cardioprotective MMPIs should be continued with different dose ranges in the study of hypercholesterolemia and other comorbidities.

scholarly journals Matrix Metalloproteinase-2 Contributes to Ischemia-Reperfusion Injury in the Heart

Circulation ◽  
2000 ◽  
Vol 101 (15) ◽  
pp. 1833-1839 ◽  
Author(s):  
Po-Yin Cheung ◽  
Grzegorz Sawicki ◽  
Mieczyslaw Wozniak ◽  
Wenjie Wang ◽  
Marek W. Radomski ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Matrix Metalloproteinase 2

scholarly journals Distribution and activation of matrix metalloproteinase-2 in skeletal muscle fibers

2019 ◽  
Vol 317 (3) ◽  
pp. C613-C625 ◽  
Author(s):  
Xiaoyu Ren ◽  
Graham D. Lamb ◽  
Robyn M. Murphy
Keyword(s):  
Skeletal Muscle ◽  
Matrix Metalloproteinase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Intracellular Localization ◽  
Muscle Fibers ◽  
Matrix Metalloproteinase 2 ◽  
Absolute Amount ◽  
Skinned Muscle ◽  
Functional Relevance

A substantial intracellular localization of matrix metalloproteinase 2 (MMP2) has been reported in cardiomyocytes, where it plays a role in the degradation of the contractile apparatus following ischemia-reperfusion injury. Whether MMP2 may have a similar function in skeletal muscle is unknown. This study determined that the absolute amount of MMP2 is similar in rat skeletal and cardiac muscle and human muscle (~10–18 nmol/kg muscle wet wt) but is ~50- to 100-fold less than the amount of calpain-1. We compared mechanically skinned muscle fibers, where the extracellular matrix (ECM) is completely removed, with intact fiber segments and found that ~30% of total MMP2 was associated with the ECM, whereas ~70% was inside the muscle fibers. Concordant with whole muscle fractionation, further separation of skinned fiber segments into cytosolic, membranous, and cytoskeletal and nuclear compartments indicated that ~57% of the intracellular MMP2 was freely diffusible, ~6% was associated with the membrane, and ~37% was bound within the fiber. Under native zymography conditions, only 10% of MMP2 became active upon prolonged (17 h) exposure to 20 μM Ca2+, a concentration that would fully activate calpain-1 in seconds to minutes; full activation of MMP2 would require ~1 mM Ca2+. Given the prevalence of intracellular MMP2 in skeletal muscle, it is necessary to investigate its function using physiological conditions, including isolation of any potential functional relevance of MMP2 from that of the abundant protease calpain-1.

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