El-Armouche, Ali

[["dc.bibliographiccitation.firstpage","1150"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Circulation Research"],["dc.bibliographiccitation.lastpage","U215"],["dc.bibliographiccitation.volume","107"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Fluschnik, Nina"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Ort, Katharina R."],["dc.contributor.author","Neef, Stefan"],["dc.contributor.author","Schulte, Timo"],["dc.contributor.author","Wittkoepper, Katrin"],["dc.contributor.author","Renner, André"],["dc.contributor.author","Schmitto, Jan D."],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:45:15Z"],["dc.date.available","2017-09-07T11:45:15Z"],["dc.date.issued","2010"],["dc.description.abstract","Rationale: Heart failure (HF) is known to be associated with increased Ca2+/calmodulin-dependent protein kinase (CaMK)II expression and activity. There is still controversial discussion about the functional role of CaMKII in HF. Moreover, CaMKII inhibition has never been investigated in human myocardium. Objective: We sought to investigate detailed CaMKII delta expression in end-stage failing human hearts (dilated and ischemic cardiomyopathy) and the functional effects of CaMKII inhibition on contractility. Methods and Results: Expression analysis revealed that CaMKII delta, both cytosolic delta(C) and nuclear delta(B) splice variants, were significantly increased in both right and left ventricles from patients with dilated or ischemic cardiomyopathy versus nonfailing. Experiments with isometrically twitching trabeculae revealed significantly improved force frequency relationships in the presence of CaMKII inhibitors (KN-93 and AIP). Increased postrest twitches after CaMKII inhibition indicated an improved sarcoplasmic reticulum (SR) Ca2+ loading. This was confirmed in isolated myocytes by a reduced SR Ca2+ spark frequency and hence SR Ca2+ leak, resulting in increased SR Ca2+ load when inhibiting CaMKII. Ryanodine receptor type 2 phosphorylation at Ser2815, which is known to be phosphorylated by CaMKII thereby contributing to SR Ca2+ leak, was found to be markedly reduced in KN-93-treated trabeculae. Interestingly, CaMKII inhibition did not influence contractility in nonfailing sheep trabeculae. Conclusions: The present study shows for the first time that CaMKII inhibition acutely improves contractility in human HF where CaMKII delta expression is increased. The mechanism proposed consists of a reduced SR Ca2+ leak and consequently increased SR Ca2+ load. Thus, CaMKII inhibition appears to be a possible therapeutic option for patients with HF and merits further investigation. (Circ Res. 2010;107:1150-1161.)"],["dc.identifier.doi","10.1161/CIRCRESAHA.110.220418"],["dc.identifier.gro","3142840"],["dc.identifier.isi","000283583400015"],["dc.identifier.pmid","20814023"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6154"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/288"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0009-7330"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Inhibition of Elevated Ca2+/Calmodulin-Dependent Protein Kinase II Improves Contractility in Human Failing Myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","621"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Circulation Heart Failure"],["dc.bibliographiccitation.lastpage","627"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Ouchi, Noriyuki"],["dc.contributor.author","Tanaka, Komei"],["dc.contributor.author","Doros, Gheorghe"],["dc.contributor.author","Wittkoepper, Katrin"],["dc.contributor.author","Schulze, Thomas"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Walsh, Kenneth"],["dc.contributor.author","Sam, Flora"],["dc.date.accessioned","2018-11-07T08:52:26Z"],["dc.date.available","2018-11-07T08:52:26Z"],["dc.date.issued","2011"],["dc.description.abstract","Background-Follistatin-like 1 (FSTL1) is an extracellular glycoprotein found in human serum. Recent work suggests that FSTL1 is secreted in response to ischemic injuries and that its overexpression is protective in the heart and vasculature. Methods and Results-We examined serum FSTL1 levels in patients with chronic heart failure with left ventricular (LV) ejection fraction <40% (n=86). The sample was separated into three tertiles of patients with low, medium, and high FSTL1 levels. Serum FSTL1 was increased 56% above age-and sex-matched healthy controls. Diabetes mellitus, brain natriuretic peptide level, left atrial size, LV posterior wall thickness, LV end-diastolic diameter, and LV mass were significant determinants of FSTL1 serum levels by bivariate analysis. After controlling for significant covariates, FSTL1 levels predicted LV hypertrophy (as measured by LV mass index) by multivariate linear regression analysis (P<0.001). Unadjusted survival analysis demonstrated increased mortality in patients with increasing FSTL1 levels (P=0.09). After adjusting for significant parameters, patients with increased FSTL1 remained at the highest risk of death (hazard ratio, 1.028; 95% CI, 0.98 to 1.78; P=0.26). To determine whether elevated FSTL1 levels may be derived from the myocardium, FSTL1 protein expression was measured in explanted failing (n=18) and nonfailing (n=7) human hearts. LV failing hearts showed 2.5-fold higher FSTL1 protein levels over nonfailing control hearts (P<.05). Conclusions-Elevated serum FSTL1 in patients with heart failure was associated with LV hypertrophy. Further studies on the role of FSTL1 as a biomarker in chronic systolic heart failure are warranted. (Circ Heart Fail. 2011;4:621-627.)"],["dc.description.sponsorship","National Heart, Lung, and Blood Institute [HL102631, HL079099]"],["dc.identifier.doi","10.1161/CIRCHEARTFAILURE.110.960625"],["dc.identifier.isi","000295035000015"],["dc.identifier.pmid","21622850"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8227"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22163"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1941-3289"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Follistatin-Like 1 in Chronic Systolic Heart Failure A Marker of Left Ventricular Remodeling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","569"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.lastpage","571"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Wittkoepper, Katrin"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2018-11-07T08:39:30Z"],["dc.date.available","2018-11-07T08:39:30Z"],["dc.date.issued","2010"],["dc.identifier.doi","10.1007/s00395-010-0107-2"],["dc.identifier.isi","000280647500001"],["dc.identifier.pmid","20526608"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/4984"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19012"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","0300-8428"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Phosphatase-1-inhibitor-1: amplifier or attenuator of catecholaminergic stress?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]