Remodeling in the ischemic heart: the stepwise progression for heart

Mill, José Geraldo; Stefanon, Ivanita; Santos, Leonardo dos; Baldo, Marcelo Perim

doi:10.1590/s0100-879x2011007500096

Cited by 70 publications

(47 citation statements)

References 57 publications

(62 reference statements)

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“…Cardiomyocyte apoptosis and fibrosis initiated by an infarct result in continuing adverse remodeling of the myocardium, which leads to eventual heart failure [2,3]. Current therapies for MI focus mostly on disease management and prevention of MI recurrence.…”

Section: Introductionmentioning

confidence: 99%

Temporary, Systemic Inhibition of the WNT/β-Catenin Pathway promotes Regenerative Cardiac Repair following Myocardial Infarct

Bastakoty

Saraswati

Joshi

et al. 2016

Cell Stem Cells Regen Med

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Aims The WNT/β-catenin pathway is temporarily activated in the heart following myocardial infarction (MI). Despite data from genetic models indicating both positive and negative roles for the WNT pathway depending on the model used, the effect of therapeutic inhibition of WNT pathway on post-injury outcome and the cellular mediators involved are not completely understood. Using a newly available, small molecule, GNF-6231, which averts WNT pathway activation by blocking secretion of all WNT ligands, we sought to investigate whether therapeutic inhibition of the WNT pathway temporarily after infarct can mitigate post injury cardiac dysfunction and fibrosis and the cellular mechanisms responsible for the effects. Methods and Results Pharmacologic inhibition of the WNT pathway by post-MI intravenous injection of GNF-6231 in C57Bl/6 mice significantly reduced the decline in cardiac function (Fractional Shortening at day 30: 38.71 ± 4.13% in GNF-6231 treated vs. 34.89 ± 4.86% in vehicle-treated), prevented adverse cardiac remodeling, and reduced infarct size (9.07 ± 3.98% vs. 17.18 ± 4.97%). WNT inhibition augmented proliferation of interstitial cells, particularly in the distal myocardium, inhibited apoptosis of cardiomyocytes, and reduced myofibroblast proliferation in the peri-infarct region. In vitro studies showed that WNT inhibition increased proliferation of Sca1+ cardiac progenitors, improved survival of cardiomyocytes, and inhibited collagen I synthesis by cardiac myofibroblasts. Conclusion Systemic, temporary pharmacologic inhibition of the WNT pathway using an orally bioavailable drug immediately following MI resulted in improved function, reduced adverse remodeling and reduced infarct size in mice. Therapeutic WNT inhibition affected multiple aspects of infarct repair: it promoted proliferation of cardiac progenitors and other interstitial cells, inhibited myofibroblast proliferation, improved cardiomyocyte survival, and reduced collagen I gene expression by myofibroblasts. Our data point to a promising role for WNT inhibitory therapeutics as a new class of drugs to drive post-MI repair and prevent heart failure.

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Section: Introductionmentioning

confidence: 99%

Temporary, Systemic Inhibition of the WNT/β-Catenin Pathway promotes Regenerative Cardiac Repair following Myocardial Infarct

Bastakoty

Saraswati

Joshi

et al. 2016

Cell Stem Cells Regen Med

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“…A major goal for cardiovascular medicine is to develop improved approaches to prevent electrical remodeling and arrhythmias, which are characteristic of ischemic heart disease [50,51].…”

Section: Arrhythmiamentioning

confidence: 99%

Cardinal roles of miRNA in cardiac development and disease

Feng

2011

Sci. China Life Sci.

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MicroRNAs (miRNAs) are small noncoding RNAs that are emerging as pivotal modulators in virtually all aspects of cardiac biology, from cardiac development to cardiomyocyte survival and hypertrophy. The miRNA profiling, following gain-and loss-of-function studies using in vitro and in vivo models, has identified wide-ranging functions for miRNAs in the heart, providing new perspectives on their contributions to cardiac pathogenesis, and revealing potential therapeutic targets and diagnostic biomarkers. This review summarizes current progress in regulation of miRNAs in heart development and disease. miRNA, cardiac, development, disease Citation:Feng Y L, Yu X Y. Cardinal roles of miRNA in cardiac development and disease.

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“…Acute MI causes a reduction in the pumping capacity of the heart, which reduces the cardiac output and blood pressure (BP). These changes are directly related to the area of the left ventricle affected by the ischemic damage (2,3). …”

Section: Introductionmentioning

confidence: 99%

“…Within the first hours after coronary occlusion, ischemic cardiac tissue undergoes cell death due to necrosis and apoptosis (2,4). Cardiac cells from the ischemic region become unable to exert their contractile function.…”

Section: Introductionmentioning

confidence: 99%

Time course of changes in heart rate and blood pressure variability in rats with myocardial infarction

Aires

Pimentel

Forechi

et al. 2017

Braz J Med Biol Res

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Our aim was to determine the time course of changes in autonomic balance in the acute (1 and 3 days), sub-acute (7 days) and chronic (28 days) phases of myocardial infarction (MI) in rats. Autonomic balance was assessed by temporal and spectral analyses of blood pressure variability (BPV) and heart rate variability (HRV). Pulsatile blood pressure (BP) recordings (30 min) were obtained in awake and unrestrained male Wistar rats (N = 77; 8-10 weeks old) with MI (coronary ligature) or sham operation (SO). Data are reported as means±SE. The high frequency (HF) component (n.u.) of HRV was significantly lower in MI-1- (P<0.01) and MI-3-day rats (P<0.05) than in their time-control groups (SO-1=68±4 vs MI-1=35.3±4.3; SO-3=71±5.8 vs MI-3=45.2±3.8), without differences thereafter (SO-7=69.2±4.8 vs MI-7=56±5.8; SO-28=73±4 vs MI-28=66±6.6). A sharp reduction (P<0.05) of BPV (mmHg2) was observed in the first week after MI (SO-1=8.55±0.80; SO-3=9.11±1.08; SO-7=7.92±1.10 vs MI-1=5.63±0.73; MI-3=5.93±0.30; MI-7=5.30±0.25). Normal BPV, however, was observed 4 weeks after MI (SO-28=8.60±0.66 vs MI-28=8.43±0.56 mmHg2; P>0.05). This reduction was mainly due to attenuation of the low frequency (LF) band of BPV in absolute and normalized units (SO-1=39.3±7%; SO-3=55±4.5%; SO-7=46.8±4.5%; SO-28=45.7±5%; MI-1=13±3.5%; MI-3=35±4.7%; MI-7=25±2.8%; MI-28=21.4±2.8%). The results suggest that the reduction in HRV was associated with decrease of the HF component of HRV suggesting recovery of the vagal control of heartbeats along the post-infarction healing period. The depression of BPV was more dependent on the attenuation of the LF component, which is linked to the baroreflex modulation of the autonomic balance.

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Remodeling in the ischemic heart: the stepwise progression for heart

Cited by 70 publications

References 57 publications

Temporary, Systemic Inhibition of the WNT/β-Catenin Pathway promotes Regenerative Cardiac Repair following Myocardial Infarct

Temporary, Systemic Inhibition of the WNT/β-Catenin Pathway promotes Regenerative Cardiac Repair following Myocardial Infarct

Cardinal roles of miRNA in cardiac development and disease

Time course of changes in heart rate and blood pressure variability in rats with myocardial infarction

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