scholarly journals Value of miR-30d and miR-146a as Prognostic Biomarkers for Heart Failure Development Post Myocardial Infarction

2021 ◽  
pp. 1-7
Author(s):  
Ana S. Holley ◽  
Ana S. Holley ◽  
Kirsty M. Danielson ◽  
Scott A. Harding ◽  
Peter D. Larsen
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Left Ventricular ◽  
Post Myocardial Infarction ◽  
Regulatory Function ◽  
Roc Curve Analysis ◽  
Markers Of Inflammation ◽  
Early Predictors ◽  
Inflammatory Processes ◽  
Control Study

Introduction: The development of heart failure (HF) following an acute myocardial infarction (AMI) is common and associated with poor clinical outcomes. In this context, the early identification of left ventricular remodelling that ultimately leads to HF remains challenging, with current biomarkers underperforming, and plasma microRNAs (miRs) have been proposed as functional biomarkers. Fibrotic and inflammatory processes are implicated in pathogenic remodelling, and miR-30d and miR-146a are reported to have regulatory function in these processes. This study aimed to determine if circulating levels of these miRs could be early predictors of HF development post myocardial infarction. Method: We conducted a case-control study with 46 AMI patients who developed HF within 1 year (cases) matched with control AMI patients (1:2 ratio) who did not develop HF and measured plasma miRs via quantitative reverse transcription polymerase chain reaction. Results: miR-30d was significantly upregulated in cases compared to controls (p<0.05), whereas miR-146a was not significantly different (p=0.57). ROC curve analysis for miR-30d demonstrated a modest sensitivity and specificity for this prediction (AUC=0.61, p<0.05). However, once adjusted for confounding factors such as atrial fibrillation and markers of inflammation, miR-30d was not found to be independently associated with HF development post myocardial infarction (OR 1.12 95% CI 0.99-1.27, p=0.08). Conclusion: miR-30d and markers of inflammation were significantly elevated in patients who developed HF within 1 year of their AMI. Further research is needed to determine the regulatory role that miR-30d may play in HF and the utility it may have as a prognostic marker in this setting.

scholarly journals Role of P2X purinergic receptors in the rescue of ischemic heart failure

2008 ◽  
Vol 295 (3) ◽  
pp. H1191-H1197 ◽  
Author(s):  
Dmitry Sonin ◽  
Si-Yuan Zhou ◽  
Chunxia Cronin ◽  
Tatiana Sonina ◽  
Jeffrey Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Infarct Size ◽  
Purinergic Receptors ◽  
P2x Receptors ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Post Myocardial Infarction ◽  
Ischemic Heart Failure

Evidence is accumulating to support the presence of P2X purinergic receptors in the heart. However, the biological role of this receptor remains to be defined. The objectives here were to determine the role of cardiac P2X receptors in modulating the progression of post-myocardial infarction ischemic heart failure and to investigate the underlying mechanism. The P2X4 receptor (P2X4R) is an important subunit of native cardiac P2X receptors, and the cardiac-specific transgenic overexpression of P2X4R (Tg) was developed as a model. Left anterior descending artery ligation resulted in similar infarct size between Tg and wild-type (WT) mice ( P > 0.1). However, Tg mice showed an enhanced cardiac contractile performance at 7 days, 1 mo, and 2 mo after infarction and an increased survival at 1 and 2 mo after infarction ( P < 0.01). The enhanced intact heart function was manifested by a greater global left ventricular developed pressure and rate of contraction of left ventricular pressure in vitro and by a significantly increased fractional shortening and systolic thickening in the noninfarcted region in vivo ( P < 0.05). The salutary effects on the ischemic heart failure phenotype were seen in both sexes and were not the result of any difference in infarct size in Tg versus WT hearts. An enhanced contractile function of the noninfarcted area in the Tg heart was likely an important rescuing mechanism. The cardiac P2X receptor is a novel target to treat post-myocardial infarction ischemic heart failure.

Abstract 18592: Anti-arrhythmic Effect of a Novel Rycal, S44121 / Arm036, in a Post-myocardial Infarction Mouse Model of Heart Failure

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jerome Thireau ◽  
Charlotte Farah ◽  
Muriel Bouly ◽  
Jerome Roussel ◽  
Alain Lacampagne ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Mouse Model ◽  
Ryanodine Receptors ◽  
Left Ventricular ◽  
Cardiac Contraction ◽  
Post Myocardial Infarction ◽  
Coronary Artery Ligation ◽  
Artery Ligation

Introduction: Targeting leaky cardiac ryanodine receptors (RyR2) to prevent diastolic Ca2+ release from the sarcoplasmic reticulum (SR) is a promising pharmacological approach, to rescue the impaired cardiac contraction and prevent Ca2+-dependent arrhythmias in heart failure (HF) and disease. Hypothesis: Based on prior work from the Marks group, the Rycal S44121 (also known as ARM036) is an experimental small molecule stabilizer of RyR. We investigated the effects of S44121 in a post-myocardial infarction (PMI) mouse model of HF. Methods and results: Mice were randomly assigned to 3 groups: Sham, PMI (subjected to left coronary artery ligation), and PMI-S (treated for 3 weeks with S44121 by subcutaneous osmotic pumps on day 7 post-MI, 10 mg/kg/day). Intracellular Ca2+ was measured on single left ventricular myocytes. PMI mice exhibited a 4-fold increase in the frequency of spontaneous Ca2+ release events, Ca2+ sparks, as measured in quiescent cells using the fluorescent Ca2+ indicator Fluo-4. PMI mice also exhibited higher global diastolic Ca2+, measured with the ratiometric fluorescent probe, Indo-1 AM, and increased the occurrence of ectopic diastolic Ca2+ waves. Acute application of S44121 (10 μM for 15 min) reduced Ca2+ sparks frequency. Chronic treatment of mice with S44121 also normalized the frequency of Ca2+ sparks and of ectopic Ca2+ waves, and corrected diastolic cellular Ca2+ overload. Effects were maximal at 20 mg/kg/day. Furthermore, treatment with S44121 abolished Ca2+ waves promoted by β-adrenergic challenge (acute application of isoproterenol, 10 nM). The potential anti-arrhythmic benefit of S44121 was assessed in vivo using telemetric surface electrocardiograms. S44121 had no effect on ECG intervals and did not alter the heart rate. However, anti-arrhythmic effects were confirmed by observation of a dose-dependent reduction of spontaneous ventricular extrasystoles and ventricular tachycardia. Near maximum benefits were observed at 10 mg/kg/day, both in basal conditions or following a challenge with acute treatment of isoproterenol (0.5 mg/kg, dosed ip). Conclusion: In mice with post-ischemic HF, treatment with S44121 prevented the abnormal diastolic SR Ca2+ leak and ectopic Ca2+ waves, and reduced ventricular arrhythmias.

scholarly journals Prevention of left ventricular remodeling after myocardial infarction: efficacy of physical training

2016 ◽  
Vol 70 (2) ◽  
Author(s):  
Camillo Taglieri ◽  
Enrico Lombardo ◽  
Mauro Feola
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Physical Training ◽  
Angiotensin Receptor Blockers ◽  
Left Ventricular ◽  
Post Myocardial Infarction ◽  
Cardiac Remodelling ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Positive Effect

Post-myocardial infarction left ventricular remodelling should be considered an important therapeutic target in patients after an acute myocardial infarction, considering the heavy prognostic implication. The therapies used in these patients should reduce the progression of the left ventricular dysfunction to refractory heart failure. In order to prevent post-myocardial infarction cardiac remodelling, different therapies have been tested, and for ACE-inhibitors and betablockers a clear demonstration of efficacy has been obtained. Losartan and valsartan, two widely used angiotensin receptor blockers, demonstrated to be safe and equally useful compared to ACEI. The addition of spironolactone to the standard therapy for heart failure has a clear beneficial effect but the clinical use has been refrained by the risk of iperkaliemia. Aerobic physical training improves the left ventricular ejection fraction in patients with systolic dysfunction, reducing the progressive enlargement after myocardial infarction. The positive effect of aerobic training on cardiac remodelling might be related to the positive effect on neurhormonal assessment, to he improvement of microcirculatory myocardial perfusion and of endothelial function.

scholarly journals Exercise Training Stabilizes RyR2-Dependent Ca2+ Release in Post-infarction Heart Failure

2021 ◽  
Vol 7 ◽  
Author(s):  
Tore Kristian Danielsen ◽  
Mani Sadredini ◽  
Ravinea Manotheepan ◽  
Jan Magnus Aronsen ◽  
Michael Frisk ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Exercise Training ◽  
Radioligand Binding ◽  
Left Ventricular ◽  
Post Myocardial Infarction ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Ventricular Cardiomyocytes ◽  
Male Wistar Rats

Aim: Dysfunction of the cardiac ryanodine receptor (RyR2) is an almost ubiquitous finding in animal models of heart failure (HF) and results in abnormal Ca2+ release in cardiomyocytes that contributes to contractile impairment and arrhythmias. We tested whether exercise training (ET), as recommended by current guidelines, had the potential to stabilize RyR2-dependent Ca2+ release in rats with post-myocardial infarction HF.Materials and Methods: We subjected male Wistar rats to left coronary artery ligation or sham operations. After 1 week, animals were characterized by echocardiography and randomized to high-intensity interval ET on treadmills or to sedentary behavior (SED). Running speed was adjusted based on a weekly VO2max test. We repeated echocardiography after 5 weeks of ET and harvested left ventricular cardiomyocytes for analysis of RyR2-dependent systolic and spontaneous Ca2+ release. Phosphoproteins were analyzed by Western blotting, and beta-adrenoceptor density was quantified by radioligand binding.Results: ET increased VO2max in HF-ET rats to 127% of HF-SED (P &lt; 0.05). This coincided with attenuated spontaneous SR Ca2+ release in left ventricular cardiomyocytes from HF-ET but also reduced Ca2+ transient amplitude and slowed Ca2+ reuptake during adrenoceptor activation. However, ventricular diameter and fractional shortening were unaffected by ET. Analysis of Ca2+ homeostasis and major proteins involved in the regulation of SR Ca2+ release and reuptake could not explain the attenuated spontaneous SR Ca2+ release or reduced Ca2+ transient amplitude. Importantly, measurements of beta-adrenoceptors showed a normalization of beta1-adrenoceptor density and beta1:beta2-adrenoceptor ratio in HF-ET.Conclusion: ET increased aerobic capacity in post-myocardial infarction HF rats and stabilized RyR2-dependent Ca2+ release. Our data show that these effects of ET can be gained without major alterations in SR Ca2+ regulatory proteins and indicate that future studies should include upstream parts of the sympathetic signaling pathway.

Early Remodeling Strain Levels Can Predict the Progression of Remodeling of the Left Ventricle Post Myocardial Infarction

2010 ◽  
Author(s):  
Emily Engel ◽  
Zhongjun J. Wu ◽  
Bartley P. Griffith
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Left Ventricle ◽  
Surgical Intervention ◽  
Left Ventricular ◽  
Post Myocardial Infarction ◽  
Loading Conditions ◽  
Lv Dysfunction ◽  
Pumping Function

Over one million patients are affected with left ventricular (LV) injury annually after sustaining a myocardial infarction (MI). In order to compensate for the loss in pumping function, the heart undergoes changes meant to maintain homeostasis. This process actually leads to a remodeling process that is initially compensatory and later becomes maladaptive. Remodeling after MI often involves loss of contractility and hypertrophy of the LV in response to increased loading conditions. Some patients are able to recover with the use of medicine and surgical intervention. However, others experience a progression of the remodeling process which leads to LV dysfunction and heart failure as the heart becomes more spherical and loses its ability to effectively contract. [1]

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