scholarly journals Alterations in ACE and ACE2 Activities and Cardiomyocyte Signaling Underlie Improved Myocardial Function in a Rat Model of Repeated Remote Ischemic Conditioning

2021 ◽  
Vol 22 (20) ◽  
pp. 11064
Author(s):  
Beáta Bódi ◽  
Patrick M. Pilz ◽  
Lilla Mártha ◽  
Miriam Lang ◽  
Ouafa Hamza ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Troponin I ◽  
Systolic Function ◽  
Limb Ischemia ◽  
Left Ventricular ◽  
Converting Enzyme ◽  
Sprague Dawley ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Lv Remodeling

Post-ischemic left ventricular (LV) remodeling and its hypothetical prevention by repeated remote ischemic conditioning (rRIC) in male Sprague–Dawley rats were studied. Myocardial infarction (MI) was evoked by permanent ligation of the left anterior descending coronary artery (LAD), and myocardial characteristics were tested in the infarcted anterior and non-infarcted inferior LV regions four and/or six weeks later. rRIC was induced by three cycles of five-minute-long unilateral hind limb ischemia and five minutes of reperfusion on a daily basis for a period of two weeks starting four weeks after LAD occlusion. Sham operated animals served as controls. Echocardiographic examinations and invasive hemodynamic measurements revealed distinct changes in LV systolic function between four and six weeks after MI induction in the absence of rRIC (i.e., LV ejection fraction (LVEF) decreased from 52.8 ± 2.1% to 50 ± 1.6%, mean ± SEM, p < 0.05) and in the presence of rRIC (i.e., LVEF increased from 48.2 ± 4.8% to 55.2 ± 4.1%, p < 0.05). Angiotensin-converting enzyme (ACE) activity was about five times higher in the anterior LV wall at six weeks than that in sham animals. Angiotensin-converting enzyme 2 (ACE2) activity roughly doubled in post-ischemic LVs. These increases in ACE and ACE2 activities were effectively mitigated by rRIC. Ca2+-sensitivities of force production (pCa50) of LV permeabilized cardiomyocytes were increased at six weeks after MI induction together with hypophosphorylation of 1) cardiac troponin I (cTnI) in both LV regions, and 2) cardiac myosin-binding protein C (cMyBP-C) in the anterior wall. rRIC normalized pCa50, cTnI and cMyBP-C phosphorylations. Taken together, post-ischemic LV remodeling involves region-specific alterations in ACE and ACE2 activities together with changes in cardiomyocyte myofilament protein phosphorylation and function. rRIC has the potential to prevent these alterations and to improve LV performance following MI.

Angiotensin-converting enzyme inhibitor captopril prevents volume overload cardiomyopathy in experimental chronic aortic valve regurgitation

2004 ◽  
Vol 82 (3) ◽  
pp. 191-199 ◽  
Author(s):  
Eric Plante ◽  
Martin Gaudreau ◽  
Dominic Lachance ◽  
Marie-Claude Drolet ◽  
Élise Roussel ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitor ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Volume Overload ◽  
Left Ventricular ◽  
Lv Function ◽  
Mrna Levels ◽  
Converting Enzyme

The efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of chronic aortic regurgitation (AR) is not well established and remains controversial. The mechanisms by which ACEIs may protect against left-ventricular (LV) volume overload are not well understood, and clinical trials performed until now have yielded conflicting results. This study was therefore performed to assess the effectiveness of two different doses of the ACEI captopril in a rat model of chronic AR. We compared the effects of a 6-month low-dose (LD) (25 mg/kg) or higher dose (HD) (75 mg/kg) treatment with captopril on LV function and hypertrophy in Wistar rats with severe AR. Untreated animals developed LV eccentric hypertrophy and systolic dysfunction. LD treatment did not prevent hypertrophy and provided modest protection against systolic dysfunction. HD treatment preserved LV systolic function and dimensions and tended to slow hypertrophy. The cardiac index remained high and similar among all AR groups, treated or not. Tissue renin–angiotensin system (RAS) analysis revealed that ACE activity was increased in the LVs of AR animals and that only HD treatment significantly decreased angiotensin II receptor mRNA levels. Fibronectin expression was increased in the LV or AR animals, but HD treatment almost completely reversed this increase. The ACE inhibitor captopril was effective at high doses in this model of severe AR. These effects might be related to the modulation of tissue RAS and the control of fibrosis.Key words: aortic valve, insufficiency, rat, echocardiography, volume overload, ACE inhibitors.

scholarly journals Polymorphisms of the angiotensin-converting enzyme and angiotensinogen gene in patients with atrial fibrillation

2011 ◽  
Vol 12 (4) ◽  
pp. 549-556 ◽  
Author(s):  
Nurdan Papila Topal ◽  
Beste Ozben ◽  
Veysel Sabri Hancer ◽  
Azra Meryem Tanrikulu ◽  
Reyhan Diz-Kucukkaya ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Angiotensin Converting Enzyme ◽  
Left Atrium ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Ras Genes ◽  
Angiotensinogen Gene ◽  
M235t Polymorphism

Activation of the renin–angiotensin system (RAS) is associated with atrial fibrillation (AF). The aim of this study was to investigate the relation between AF and polymorphisms in RAS. One hundred and fifty patients with AF, 100 patients with no documented episode of AF and 100 healthy subjects were consecutively recruited into the study. The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and the M235T, A-20C, and G-6A polymorphisms of the angiotensinogen gene were genotyped. Patients with AF had significantly lower frequency of II genotype of ACE I/D and higher frequency of angiotensinogen M235T polymorphism T allele and TT genotype and G-6A polymorphism G allele and GG genotype compared with the controls. AF patients had significantly larger left atrium, higher left ventricular mass index (LVMI) and higher frequency of significant valvular pathology. ACE I/D polymorphism II genotype, angiotensinogen M235T polymorphism TT genotype and G allele and GG genotype of angiotensinogen G-6A polymorphism were still independently associated with AF when adjusted for left atrium, LVMI and presence of significant valvular pathology. Genetic predisposition might be underlying the prevalence of acquired AF. Patients with a specific genetic variation in the RAS genes may be more liable to develop AF.

scholarly journals Effect of angiotensin-converting enzyme gene polymorphism on left ventricular remodeling after anteroseptal infarction

1999 ◽  
Vol 22 (9) ◽  
pp. 587-590 ◽  
Author(s):  
Junzo Nagashima ◽  
Tomoyuki Kunishima ◽  
Sachihiko Nobuoka ◽  
Masahiro Murayama ◽  
Haruki Musha ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Angiotensin Converting Enzyme ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Angiotensin Converting Enzyme Gene ◽  
Converting Enzyme ◽  
Enzyme Gene

scholarly journals Association of Angiotensin Converting Enzyme Gene Polymorphisms with Left Ventricular Hypertrophy

2005 ◽  
Vol 28 (4) ◽  
pp. 345-349 ◽  
Author(s):  
Mohammad SAEED ◽  
Danish SALEHEEN ◽  
Sammer SIDDIQUI ◽  
Aisha KHAN ◽  
Zahid A. BUTT ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Angiotensin Converting Enzyme ◽  
Gene Polymorphisms ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Angiotensin Converting Enzyme Gene ◽  
Converting Enzyme ◽  
Enzyme Gene

scholarly journals Contractile protein phosphorylation predicts human heart disease phenotypes

2013 ◽  
Vol 304 (12) ◽  
pp. H1644-H1650 ◽  
Author(s):  
Lori A. Walker ◽  
David A. Fullerton ◽  
Peter M. Buttrick
Keyword(s):  
Heart Failure ◽  
Heart Disease ◽  
Protein Phosphorylation ◽  
Protein Phosphatase ◽  
Human Heart ◽  
Troponin I ◽  
Systolic Function ◽  
Left Ventricular ◽  
Control Group ◽  
Lv Function

Human heart failure has been associated with a low level of thin-filament protein phosphorylation and an increase in calcium sensitivity of contraction relative to both “control” human heart tissue and tissue from small animal models. However, diverse strategies of human tissue procurement and the reliance on tissue obtained from subjects with end-stage heart failure suggest this may be an incomplete characterization. Therefore, we evaluated cardiac left ventricular (LV) biopsy samples from patients with aortic stenosis undergoing valve replacement who presented either with LV hypertrophy and preserved systolic function (Hyp) or with LV dilation and reduced ejection fraction (Dil). In Hyp, total troponin I (TnI) phosphorylation was markedly increased and myosin light chain 2 (MLC2) phosphorylation was unchanged relative to a control group of patients with normal LV function. Conversely, in Dil, total TnI phosphorylation was significantly reduced compared with control subjects and MLC2 phosphorylation was increased. Site-specific analysis of TnI phosphorylation revealed phenotype-specific differences such that Hyp samples demonstrated significant increases in phosphorylation at serine 22/23 and Dil samples had significant decreases at serine 43. The ratio of phosphorylation at the two sites was biased toward serine 22/23 in Hyp and toward serine 43/45 in Dil. Western blot analysis showed that protein phosphatase-1 was reduced in Hyp and protein phosphatase-2 was reduced in Dil. These data suggest that posttranslational modifications of sarcomeric proteins, both singly and in combination, are stage specific. Defining these changes in progressive heart disease may provide important diagnostic and treatment information.

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