scholarly journals Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Georg D. Duerr ◽  
Daniela Dewald ◽  
Eva J. Schmitz ◽  
Luise Verfuerth ◽  
Katharina Keppel ◽  
...  
Keyword(s):  
Antioxidative Enzymes ◽  
Left Ventricular Dysfunction ◽  
Ischemic Cardiomyopathy ◽  
Ventricular Dysfunction ◽  
Interstitial Fibrosis ◽  
Myosin Heavy Chain Isoforms ◽  
Left Ventricular ◽  
Adverse Remodeling ◽  
Cardioprotective Effects

Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model ofI/R.Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT-/-)-mice (n= 8–10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies.Results. Expression of MT1/2 mRNA was transiently induced during repetitiveI/Rin WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT-/--hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2-/--hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT-/--hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2-/--hearts.Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling.

Unipolar Voltage Abnormality is Associated with Greater Left Ventricular Dysfunction in Ischemic Cardiomyopathy

2013 ◽  
Vol 25 (3) ◽  
pp. 293-298 ◽  
Author(s):  
BASHAR ALDHOON ◽  
DAVID S. FRANKEL ◽  
MATHEW D. HUTCHINSON ◽  
DAVID J. CALLANS ◽  
ANDREW E. EPSTEIN ◽  
...  
Keyword(s):  
Left Ventricular Dysfunction ◽  
Ischemic Cardiomyopathy ◽  
Ventricular Dysfunction ◽  
Left Ventricular

scholarly journals The Role of Arrhythmia and Left Ventricular Dysfunction in Patients with Acute Myocardial Infarction and Bundle Branch Block.

1993 ◽  
Vol 34 (2) ◽  
pp. 145-157 ◽  
Author(s):  
Ahmet ALPMAN ◽  
Muharrem GÜLDAL ◽  
Çetin EROL ◽  
Günes AKGÜN ◽  
Celal KERVANCIOGLU ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Left Ventricular Dysfunction ◽  
Ventricular Dysfunction ◽  
Left Ventricular ◽  
Bundle Branch Block

scholarly journals Cardioprotective Effects of Osteopontin-1 during Development of Murine Ischemic Cardiomyopathy

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Georg D. Duerr ◽  
Bettina Mesenholl ◽  
Jan C. Heinemann ◽  
Martin Zoerlein ◽  
Peter Huebener ◽  
...  
Keyword(s):  
Ischemic Cardiomyopathy ◽  
Ventricular Dysfunction ◽  
Cardiac Fibroblasts ◽  
Hibernating Myocardium ◽  
Matricellular Protein ◽  
Ischemia And Reperfusion ◽  
Myocardial Contractile ◽  
Cardioprotective Effects ◽  
Lower Expression

Repetitive brief ischemia and reperfusion (I/R) is associated with ventricular dysfunction in pathogenesis of murine ischemic cardiomyopathy and human hibernating myocardium. We investigated the role of matricellular protein osteopontin-1 (OPN) in murine model of repetitive I/R. One 15-min LAD-occlusion followed by reperfusion was performed daily over 3, 5, and 7 consecutive days in C57/Bl6 wildtype- (WT-) and OPN−/−-mice (n=8/group). After echocardiography hearts were processed for histological and mRNA-studies. Cardiac fibroblasts were isolated, cultured, and stimulated with TGF-β1. WT-mice showed an early, strong, and cardiomyocyte-specific osteopontin-expression leading to interstitial macrophage infiltration and consecutive fibrosis after 7 days I/R in absence of myocardial infarction. In contrast, OPN−/−-mice showed small, nontransmural infarctions after 3 days I/R associated with significantly worse ventricular dysfunction. OPN−/−-mice had different expression of myocardial contractile elements and antioxidative mediators and a lower expression of chemokines during I/R. OPN−/−-mice showed predominant collagen deposition in macrophage-rich small infarctions. We found lower induction of tenascin-C, MMP-9, MMP-12, and TIMP-1, whereas MMP-13-expression was higher in OPN−/−-mice. Cultured OPN−/−-myofibroblasts confirmed these findings. In conclusion, osteopontin seems to modulate expression of contractile elements, antioxidative mediators, and inflammatory response and subsequently remodel in order to protect cardiomyocytes in murine ischemic cardiomyopathy.

Sign in / Sign up

Export Citation Format

Share Document