scholarly journals Pharmacological Modulation of Cardiac Remodeling after Myocardial Infarction

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Wei Zhao ◽  
Jia Zhao ◽  
Jianhui Rong
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Drug Repositioning ◽  
Ischemia Reperfusion ◽  
Present Review ◽  
Functional Changes ◽  
Pharmacological Modulation ◽  
Complex Process ◽  
Cardiac Functions ◽  
Clinical Drugs

Cardiac remodeling describes a series of structural and functional changes in the heart after myocardial infarction (MI). Adverse post-MI cardiac remodeling directly jeopardizes the recovery of cardiac functions and the survival rate in MI patients. Several classes of drugs are proven to be useful to reduce the mortality of MI patients. However, it is an ongoing challenge to prevent the adverse effects of cardiac remodeling. The present review aims to identify the pharmacological therapies from the existing clinical drugs for the treatment of adverse post-MI cardiac remodeling. Post-MI cardiac remodeling is a complex process involving ischemia/reperfusion, inflammation, cell death, and deposition of extracellular matrix (ECM). Thus, the present review included two parts: (1) to examine the basic pathophysiology in the cardiovascular system and the molecular basis of cardiac remodeling and (2) to identify the pathological aspects of cardiac remodeling and the potential of the existing pharmacotherapies. Ultimately, the present review highlights drug repositioning as a strategy to discover effective therapies from the existing drugs against post-MI cardiac remodeling.

Abstract 327: Apelin-13 Increases Myocardial Progenitor Cells and Improves Myocardial Remodeling of Post-myocardial Infarction.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
lanfang Li ◽  
Heng Zeng ◽  
Jian-Xiong Chen
Keyword(s):  
Myocardial Infarction ◽  
Progenitor Cells ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cxcr4 Expression ◽  
Post Myocardial Infarction ◽  
Coronary Artery Ligation ◽  
Vascular Progenitor Cells

ABSTRACT: Apelin is an endogenous ligand for the angiotensin-like 1 receptor (APJ) and has beneficial effects against hypertension and myocardial ischemia/reperfusion injury. Little is known about the role of apelin in the homing of vascular progenitor cells (PCs) and cardiac remodeling post-myocardial infarction (MI). The present study investigates whether apelin affects PCs homing to the infarcted myocardium thereby mediating cardiac remodeling post-MI. Mice were infarcted by coronary artery ligation and apelin-13 (1 mg/kg.d) was injected for three days prior to MI and for either 24 hours or 14 days post MI. Homing of vascular progenitor cell (CD133 + /c-kit + /Sca1 + , CD133 + /SDF-1α + and CD133 + /CXCR4 + ) into the ischemic area were examined at 24 hours and 14 days post-MI. Myocardial Akt, eNOS, VEGF, Jagged1, Notch3, SDF-1α and CXCR4 expression were assessed. Functional analyses were performed at day 14 after MI. Mice receiving apelin-13 treatment demonstrated upregulation of SDF-1α/CXCR4 expression and dramatically increased the number of CD133 + /c-kit + /Sca1 + , CD133 + /SDF-1α + and c-kit + /CXCR4 + cells in the infarcted hearts. Apelin-13 also significantly increased Akt and eNOS phosphorylation and upregulated VEGF, Jagged1, Notch3 expression in the ischemic hearts. This was accompanied by a significant reduction of myocardial apoptosis. Further, treatment with apelin-13 promoted myocardial angiogenesis, attenuated cardiac fibrosis and hypertrophy together with a significant improvement of cardiac function at 14 days post-MI mice. Apelin-13 increases angiogenesis and improves cardiac remodeling by a mechanism involving upregulation of SDF-1α/CXCR4 and homing of vascular progenitor cells.

scholarly journals Swiprosin-1/EFhD-2 Expression in Cardiac Remodeling and Post-Infarct Repair: Effect of Ischemic Conditioning

2020 ◽  
Vol 21 (9) ◽  
pp. 3359
Author(s):  
Zoltán Giricz ◽  
András Makkos ◽  
Rolf Schreckenberg ◽  
Jochen Pöling ◽  
Holger Lörchner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Common Mechanism ◽  
Structural Adaptation ◽  
Infarct Zone ◽  
Rat Cardiomyocytes ◽  
Ischemic Conditioning

Swiprosin-1 (EFhD2) is a molecule that triggers structural adaptation of isolated adult rat cardiomyocytes to cell culture conditions by initiating a process known as cell spreading. This process mimics central aspects of cardiac remodeling, as it occurs subsequent to myocardial infarction. However, expression of swiprosin-1 in cardiac tissue and its regulation in vivo has not yet been addressed. The expression of swiprosin-1 was analyzed in mice, rat, and pig hearts undergoing myocardial infarction or ischemia/reperfusion with or without cardiac protection by ischemic pre- and postconditioning. In mouse hearts, swiprosin-1 protein expression was increased after 4 and 7 days in myocardial infarct areas specifically in cardiomyocytes as verified by immunoblotting and histology. In rat hearts, swiprosin-1 mRNA expression was induced within 7 days after ischemia/reperfusion but this induction was abrogated by conditioning. As in cultured cardiomyocytes, the expression of swiprosin-1 was associated with a coinduction of arrestin-2, suggesting a common mechanism of regulation. Rno-miR-32-3p and rno-miR-34c-3p were associated with the regulation pattern of both molecules. Moreover, induction of swiprosin-1 and ssc-miR-34c was also confirmed in the infarct zone of pigs. In summary, our data show that up-regulation of swiprosin-1 appears in the postischemic heart during cardiac remodeling and repair in different species.

Abstract 379: Inhibition of Bcl-x Phosphorylation Prevents Cardiomyocyte Death, Cardiac Remodeling and Heart Failure After Myocardial Infarction

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Michinari Nakamura ◽  
Peiyong Zhai ◽  
Dominic D Re ◽  
Junichi Sadoshima
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Remodeling ◽  
Ischemia Reperfusion ◽  
Resistant Mutant ◽  
Cardiac Contraction ◽  
Dependent Manner ◽  
Infarct Area

Cardiac remodeling promotes heart failure (HF). Cardiomyocyte (CM) death is one of the mechanisms to develop cardiac remodeling. We recently reported that Mst1 phosphorylates Bcl-xL at Ser14, which promotes apoptosis by inducing dissociation of Bcl-xL from Bax and consequent activation of Bax in CMs. Its phosphorylation is increased in response to ischemia-reperfusion (IR) in an Mst1-dependent manner. However, the functional significance of endogenous Bcl-xL phosphorylation remains unclear in vivo. To address this question, knock-in (KI) mice with alanine mutation at Ser14 in Bcl-x were generated. At baseline, cardiac function was similar between wild-type (WT) and heterozygous KI (HKI) mice (EF 76% and 79%, respectively). HKI mice exhibited smaller % infarct area (30%) than WT (43%) (p=0.016) upon IR, suggesting that phosphorylation of endogenous Bcl-xL at Ser14 plays an essential role in mediating IR injury. In order to test the role of Bcl-xL phosphorylation in the development of HF, HKI and WT mice were subjected to permanent ligation of LAD for 4 weeks. During progression of cardiac remodeling, Mst1 was activated in both WT and HKI mice. Phosphorylation of Bcl-xL and Bcl-xS, an alternative transcriptional variant of Bcl-x, both at Ser14, were increased in WT mice, which were abrogated in HKI mice. The infarct area evaluated with TTC staining at Day 1 was similar in WT and HKI mice (59.1% and 61.2%, p=0.65). Four weeks after myocardial infarction (MI), WT mice exhibited lower cardiac contraction (EF 46.5%) and higher LVEDP (10.8mmHg) than those in HKI mice (EF 68.9% and LVEDP 7.0mmHg) (both p<0.05). Scar area and TUNEL-positive CMs were greater in WT (49.0% and 1.6%, respectively) than in HKI mice (29.2% and 0.4%, respectively) (both p<0.05). Cleaved caspase 3 and 9 were significantly increased (3.2- and 5.7-fold, respectively) in WT but not in HKI mice. In vitro experiments with overexpression of phospho-mimicking mutant (Bcl-xS-S14D) showed 13% reduction in cell viability compared with that of phospho-resistant mutant (Bcl-xS-S14A) (p=0.01%). Our results suggest that phosphorylation of Bcl-xL and Bcl-xS at Ser14 contributes to CM death in response to IR and chronic MI in vivo, thereby promoting cardiac remodeling and HF.

scholarly journals Human Lysyl Oxidase Over-Expression Enhances Baseline Cardiac Oxidative Stress but Does Not Aggravate ROS Generation or Infarct Size Following Myocardial Ischemia-Reperfusion

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 75
Author(s):  
Laura Valls-Lacalle ◽  
Lídia Puertas-Umbert ◽  
Saray Varona ◽  
José Martínez-González ◽  
Cristina Rodríguez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Infarct Size ◽  
Cardiac Remodeling ◽  
Lysyl Oxidase ◽  
Ischemia Reperfusion ◽  
Ros Production ◽  
Over Expression ◽  
Myocardial Oxidative Stress ◽  
Myocardial Ischemia Reperfusion

Lysyl oxidase (LOX) is an enzyme critically involved in collagen maturation, whose activity releases H2O2 as a by-product. Previous studies demonstrated that LOX over-expression enhances reactive oxygen species (ROS) production and exacerbates cardiac remodeling induced by pressure overload. However, whether LOX influences acute myocardial infarction and post-infarct left ventricular remodeling and the contribution of LOX to myocardial oxidative stress following ischemia-reperfusion have not been analyzed. Isolated hearts from transgenic mice over-expressing human LOX in the heart (TgLOX) and wild-type (WT) littermates were subjected to global ischemia and reperfusion. Although under basal conditions LOX transgenesis is associated with higher cardiac superoxide levels than WT mice, no differences in ROS production were detected in ischemic hearts and a comparable acute ischemia-reperfusion injury was observed (infarct size: 56.24 ± 9.44 vs. 48.63 ± 2.99% of cardiac weight in WT and TgLOX, respectively). Further, similar changes in cardiac dimensions and function were observed in TgLOX and WT mice 28 days after myocardial infarction induced by transient left anterior descending (LAD) coronary artery occlusion, and no differences in scar area were detected (20.29 ± 3.10 vs. 21.83 ± 2.83% of left ventricle). Our data evidence that, although LOX transgenesis induces baseline myocardial oxidative stress, neither ROS production, infarct size, nor post-infarction cardiac remodeling were exacerbated following myocardial ischemia-reperfusion.

scholarly journals Xenon and Isoflurane Reduce Left Ventricular Remodeling after Myocardial Infarction in the Rat

2013 ◽  
Vol 118 (6) ◽  
pp. 1385-1394 ◽  
Author(s):  
Anna B. Roehl ◽  
Sandra Funcke ◽  
Michael M. Becker ◽  
Andreas Goetzenich ◽  
Christian Bleilevens ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Troponin I ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Ischemia Reperfusion ◽  
Capillary Density ◽  
Left Ventricular ◽  
Acute Injury ◽  
Perioperative Myocardial Infarction

Abstract Background: Xenon and isoflurane are known to have cardioprotective properties. We tested the hypothesis that these anesthetics positively influence myocardial remodeling 28 days after experimental perioperative myocardial infarction and compared their effects. Methods: A total of 60 male Sprague–Dawley rats were subjected to 60min of coronary artery occlusion and 120min of reperfusion. Prior to ischemia, the animals were randomized for the different narcotic regimes (0.6 vol% isoflurane, 70 vol% xenon, or intraperitoneal injection of s-ketamine). Acute injury was quantified by echocardiography and troponin I. After 4 weeks, left ventricular function was assessed by conductance catheter to quantify hemodynamic compromise. Cardiac remodeling was characterized by quantification of dilatation, hypertrophy, fibrosis, capillary density, apoptosis, and expression of fetal genes (α/β myosin heavy chains, α-skeletal actin, periostin, and sarco/endoplasmic reticulum Ca2+-ATPase). Results: Whereas xenon and isoflurane impeded the acute effects of ischemia-reperfusion on hemodynamics and myocardial injury at a comparable level, differences were found after 4 weeks. Xenon in contrast to isoflurane or ketamine anesthetized animals demonstrated a lower remodeling index (0.7±0.1 vs. 0.9±0.3 and 1.0±0.3g/ml), better ejection fraction (62±9 vs. 49±7 and 35±6%), and reduced expression of β-myosin heavy chain and periostin. The effects on hypertrophy, fibrosis, capillary density, and apoptosis were comparable. Conclusions: Compared to isoflurane and s-ketamine, xenon limited progressive adverse cardiac remodeling and contractile dysfunction 28 days after perioperative myocardial infarction.

RELATION OF THE MARKERS OF MYOCARDIAL DYSFUNCTION AND SYSTEMIC INFLAMMATION WITH STRUCTURAL AND FUNCTIONAL PARAMETERS OF THE LUNGS IN MYOCARDIAL INFARCTION PATIENTS

2018 ◽  
Vol 17 (2) ◽  
pp. 24-28
Author(s):  
O. M. Polikutina ◽  
Y. S. Slepynina ◽  
E. D. Bazdyrev ◽  
V. N. Karetnikova ◽  
O. L. Barbarach
Keyword(s):  
Myocardial Infarction ◽  
Systemic Inflammation ◽  
Myocardial Dysfunction ◽  
Control Group ◽  
Chronic Obstructive ◽  
Lung Pathology ◽  
Functional Changes ◽  
Functional Parameters ◽  
Lung Capacity ◽  
Copd Patients

Aim. To evaluate the structural and functional changes in the lungs of ST elevation myocardial infarction (STEMI) patients with absence or presence of chronic obstructive lung disease (COPD), and the relation with myocardial dysfunction and systemic inflammation.Material and methods. Totally, 189 STEMI patients included: group 1 — STEMI with COPD of moderate and mild grade, 2 — STEMI with no lung pathology. Groups were comparable by clinical and anamnestic parameters. Assessment of lung function and blood collection were done at 10­12 day of STEMI. For comparison of the parameters representing structural and functional changes in the lungs and comparison of C­reactive protein (CRP), N­terminal pro­brain natriuretic peptide (NT­proBNP) concentration, a control group was formed with no pulmonary pathology, comparable by age and sex with the STEMI patients.Results. In COPD patients, higher values revealed of the parameters representing the part of residual volumes in pulmonary structure. Higher residual volume (RV) was found also in STEMI and no COPD comparing to controls, however the relation RV/TLC (total lung capacity) was not higher than normal range. In both groups there were lower values of diffusion lung capacity (DLCO) comparing to controls. The lowest DLCO found in COPD patients. Concentration of NT­proBNP (H=41,6; p<0,001) and CRP (H=38,6; p<0,001) in COPD was significantly higher in STEMI with no COPD patients than in controls. The negative correlations found for NT­proBNP and CRP with forced expiratory volume 1 sec, FEV/FVC1, DLCO, and positive — with the values of thoracic volume, RV/TLC.Conclusion. In STEMI patients the increase revealed of residual lung volumes. Mostly the level of residual volumes is high in STEMI and COPD patients. There are associations of NT­proBNP and CRP with structural and functional parameters of the lungs regardless of COPD.

PHENOTYPIC HETEROGENEITY OF CARDIAC MACROPHAGES DURING WOUND HEALING FOLLOWING MYOCARDIAL INFARCTION: PERSPECTIVES IN CLINICAL RESEARCH

2018 ◽  
Vol 33 (2) ◽  
pp. 70-76 ◽  
Author(s):  
A. E. Gombozhapova ◽  
Yu. V. Rogovskaya ◽  
M. S. Rebenkova ◽  
J. G. Kzhyshkowska ◽  
V. V. Ryabov
Keyword(s):  
Myocardial Infarction ◽  
Wound Healing ◽  
Cardiac Remodeling ◽  
Phenotypic Heterogeneity ◽  
Macrophage Infiltration ◽  
Myocardial Regeneration ◽  
Control Group ◽  
M2 Macrophage ◽  
Inflammatory Phase ◽  
Regenerative Phase

Purpose. Myocardial regeneration is one of the most ambitious goals in prevention of adverse cardiac remodeling. Macrophages play a key role in transition from inflammatory to regenerative phase during wound healing following myocardial infarction (MI). We have accumulated data on macrophage properties ex vivo and in cell culture. However, there is no clear information about phenotypic heterogeneity of cardiac macrophages in patients with MI. The purpose of the project was to assess cardiac macrophage infiltration during wound healing following myocardial infarction in clinical settings taking into consideration experimental knowledge.Material and Methods. The study included 41 patients with fatal MI type 1. In addition to routine analysis, macrophages infiltration was assessed by immunohistochemistry. We used CD68 as a marker for the cells of the macrophage lineage, while CD163, CD206, and stabilin-1 were considered as M2 macrophage biomarkers. Nine patients who died from noncardiovascular causes comprised the control group.Results. The intensity of cardiac macrophage infiltration was higher during the regenerative phase than during the inflammatory phase. Results of immunohistochemical analysis demonstrated the presence of phenotypic heterogeneity of cardiac macrophages in patients with MI. We noticed that numbers of CD68+, CD163+, CD206+, and stabilin-1+ macrophages depended on MI phase.Conclusion. Our study supports prospects for implementation of macrophage phenotyping in clinic practice. Improved understanding of phenotypic heterogeneity might become the basis of a method to predict adverse cardiac remodeling and the first step in developing myocardial regeneration target therapy.

Sign in / Sign up

Export Citation Format

Share Document