Abstract MP215: Endothelial Colony Forming Cell Derived Exosomes Promote Angiogenesis And Cardiac Repair Post Myocardial Infarction

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Karina P Gomes ◽  
Anshul S Jadli ◽  
Ananya Parasor ◽  
Noura N Ballasy ◽  
Monica Surti ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Endothelial Cells ◽  
Ejection Fraction ◽  
Cardiac Remodeling ◽  
Cardiac Repair ◽  
Negative Regulator ◽  
Bioinformatics Analyses ◽  
Colony Forming Cell ◽  
Fractional Shortening

Background: Despite improvements in therapeutics, ischemic heart disease remains a leading cause of death. Cardiac remodeling after myocardial infarction (MI), predominantly due to loss of cardiomyocytes and coronary vasculature, leads to a progressive decline in cardiac function resulting in heart failure. Current therapies for cardiac repair and heart failure are of limited benefit. Cell transplantation therapy upon MI is a very promising therapeutic strategy to replace dead myocardium, reducing scarring and improving cardiac performance. Methods and Results: Our research focuses on endothelial colony-forming cell-derived exosomes (ECFC-exosomes), which are actively secreted endocytic nanovesicles (30-100 nm) that transport functional miRNAs, proteins, mRNAs, and lipids, playing a key role in paracrine intercellular communication. We identified a novel ability of ECFC-exosomes to promote angiogenesis and cardiac tissue repair. Administration of ECFCs to mice following experimental end-organ ischemia resulted in ECFC-exosome-dependent increase in angiogenesis. ECFC-derived exosomes were taken up by endothelial cells leading to their proliferation and migration, tube formation, and formation of new vessels. Administration of ECFC-exosome to a murine model of MI prevented cardiac remodeling and heart failure. The acute MI resulted in severely decreased left ventricle ejection fraction (Sham 71.2% ± 5 .87, MI+Saline 32.9% ± 2.32) and fractional shortening (Sham 29.5% ± 3.20, MI+Saline 13.6% ± 2.87), and the administration of ECFC-exosomes prevented MI-induced cardiac dysfunction (ejection fraction: MI+ECFC-Exo 64.3% ± 8.74; fractional shortening: MI+ECFC-Exo: 26.4% ± 3.13). Next generation sequencing and bioinformatics analyses identified 136 miRNAs present in ECFC-exosome cargo, and factor inhibiting HIF-1α and PTEN as their potential targets in endothelial cells. Increased nuclear HIF-1α levels in response to ECFC-exosome administration, which may aid in the transcriptional function of HIF-1α, corroborated the role of exosomal miRNA in myocardial angiogenesis. We also found decreased levels of PTEN in response to ECFC-exosome treatment, which is a key negative regulator of PI3K/Akt pathways, survival pathways of heart. We also identified the relative angiogenesis expression profile of the peri-infarcted area in response to ECFC-exosome treatment. The ECFC-exosome administration upregulated the levels of VEGF, IGFBP-1 and PDGF, among others proangiogenic factors, and downregulated the levels of angiostatic factors as IP-10 and Thrombospondin-2. Conclusion: Our findings support the view that the ECFC-exosomes represent a novel therapeutic approach to improve cardiac repair after MI.

scholarly journals Cardiac-Specific Overexpression of miR-222 Induces Heart Failure and Inhibits Autophagy in Mice

2016 ◽  
Vol 39 (4) ◽  
pp. 1503-1511 ◽  
Author(s):  
Ming Su ◽  
Zhiguo Chen ◽  
Changxin Wang ◽  
Lei Song ◽  
Yubao Zou ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Mtor Pathway ◽  
Negative Regulator ◽  
Internal Diameter ◽  
Specific Expression ◽  
Autophagy Inhibition ◽  
Fractional Shortening

Background: MicroRNAs play a crucial role in the regulation of pathological cardiac remodeling and heart failure. Previously, we found that overexpression of miR-221 induces heart failure in mice. The miR-222 and miR-221 share the same gene cluster, however, the role of miR-222 in the regulation of cardiac function remained ill-defined. Methods and Results: Transgenic mice with cardiac-specific expression of miR-222 (Tg-miR-222) mice were generated. The Tg-miR-222 mice developed significantly enlarged hearts at 4 weeks of age. Transthoracic echocardiograph data indicated that the hearts of Tg-miR-222 mice exhibited an increased left ventricular end-diastolic internal diameter and decreased fractional shortening. We observed that the LC3-II in Tg-miR-222 mice was decreased accompanied with the upregulation of p62, indicating the autophagy inhibition in the hearts of Tg-miR-222 mice. The mTOR pathway, a negative regulator of autophagy, was activated in the hearts of Tg-miR-222 mice. The expression of p27 was downregulated by miR-222 overexpression. Conclusion: Our data indicate that miR-222 overexpression induces heart failure in mice. The downregulation of p27 and the activation of mTOR pathway may be involved in miR-222-induced heart failure and autophagy inhibition. Thus, targeting miR-222 expression may be a therapeutic strategy against pathological cardiac remodeling.

Echocardiographic Evaluation of Cardiac Remodeling After Surgical Closure of Ventricular Septal Defect in Different Age Group

2017 ◽  
Vol 2 (2) ◽  
pp. 69-74
Author(s):  
Mohammad Aminullah ◽  
Fahmida Akter Rima ◽  
Asraful Hoque ◽  
Mokhlesur Rahman Sazal ◽  
Prodip Biswas ◽  
...  
Keyword(s):  
Ventricular Septal Defect ◽  
Ejection Fraction ◽  
Cardiac Remodeling ◽  
Septal Defect ◽  
Left Ventricular ◽  
Age Group ◽  
Surgical Closure ◽  
Group A ◽  
Group B ◽  
Fractional Shortening

Background: Cardiac remodeling is important issue after surgical closure of ventricular septal defect.Objective: The purpose of the present study was to evaluate cardiac remodeling by echocardiography by measuring the ejection fraction, fractional shortening, left ventricular internal diameter during diastole (LVIDd) and left ventricular internal diameter during systole (LVIDs) after surgical closure of ventricular septal defect in different age group. Methodology: This prospective cohort studies was conducted in the Department of Cardiac Surgery at National Institute of Cardiovascular Disease (NICVD), Dhaka. Patient with surgical closure of VSD were enrolled into this study purposively and were divided into 3 groups according to the age. In group A (n=10), patients were within the age group of 2.0 to 6.0 years; age of group B (n=8) patients were 6.1-18.0 years and the group C (n=6) aged range was 18.1-42.0 years. Echocardiographic variables such as ejection fraction, fractional shortening, LVIDd, LVIDs were taken preoperatively and at 1st and 3rd month of postoperative values. Result: A total number of 24 patients was recruited for this study. The mean ages of all groups were 12.60±12.09. After 1 month ejection fraction were decreased by 5.97%, 6.71% and 5.66% in group A, group B and group C respectively. After 3 months ejection fraction were increased by 6.13%, 5.13% and 5.14% in group A, group B and group C respectively. After 1 month fractional shortening were decreased by 13.55%, 9.30% and 9.09% in group A, group B and group C respectively. After 3 months fractional shortening were increased by 7.23%, 7.35% and 4.55% in group A, group B and group C respectively. After 1 month LVIDd were increased by 1.97%, 1.91% and 1.32% in group A, group B and group C respectively. After 3 months LVIDd were decreased by 10.84%, 9.89% and 7.34% in group A, group B and group C respectively. After 1 month LVIDs were increased by 2.19%, 2.86% and 1.98% in group A, group B and group C respectively. After 3 months LVIDs were decreased by 11.68%, 10.97% and 8.87% in group A, group B and group C respectively.Conclusion: Cardiac remodeling occurred after surgical closure of ventricular septal defect and remodeling were more significant in younger age group. Journal of National Institute of Neurosciences Bangladesh, 2016;2(2):69-74

scholarly journals Contemporary Trends in Heart Failure With Reduced and Preserved Ejection Fraction After Myocardial Infarction: A Community Study

2013 ◽  
Vol 178 (8) ◽  
pp. 1272-1280 ◽  
Author(s):  
Y. Gerber ◽  
S. A. Weston ◽  
C. Berardi ◽  
S. M. McNallan ◽  
R. Jiang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Community Study ◽  
Preserved Ejection Fraction

Risk of Heart Failure in Myocardial Infarction with Reduced, mid Range and Preserved Ejection Fraction

2017 ◽  
Vol 23 (10) ◽  
pp. S37
Author(s):  
Hiroyuki Okura ◽  
Toru Kataoka ◽  
Yoshihiko Saito ◽  
Kiyoshi Yoshida
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Preserved Ejection Fraction

scholarly journals Generation of Cardiomyocytes From Vascular Adventitia-Resident Stem Cells

2018 ◽  
Vol 123 (6) ◽  
pp. 686-699 ◽  
Author(s):  
Subba Rao Mekala ◽  
Philipp Wörsdörfer ◽  
Jochen Bauer ◽  
Olga Stoll ◽  
Nicole Wagner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Stem Cells ◽  
Endothelial Cells ◽  
Aortic Wall ◽  
Fluorescent Protein ◽  
Therapeutic Option ◽  
Cardiac Regeneration ◽  
Cardiac Progenitors ◽  
Resident Stem Cells

Rationale: Regeneration of lost cardiomyocytes is a fundamental unresolved problem leading to heart failure. Despite several strategies developed from intensive studies performed in the past decades, endogenous regeneration of heart tissue is still limited and presents a big challenge that needs to be overcome to serve as a successful therapeutic option for myocardial infarction. Objective: One of the essential prerequisites for cardiac regeneration is the identification of endogenous cardiomyocyte progenitors and their niche that can be targeted by new therapeutic approaches. In this context, we hypothesized that the vascular wall, which was shown to harbor different types of stem and progenitor cells, might serve as a source for cardiac progenitors. Methods and Results: We describe generation of spontaneously beating mouse aortic wall-derived cardiomyocytes without any genetic manipulation. Using aortic wall-derived cells (AoCs) of WT (wild type), αMHC (α-myosin heavy chain), and Flk1 (fetal liver kinase 1)-reporter mice and magnetic bead-associated cell sorting sorting of Flk1 + AoCs from GFP (green fluorescent protein) mice, we identified Flk1 + CD (cluster of differentiation) 34 + Sca-1 (stem cell antigen-1)-CD44 − AoCs as the population that gives rise to aortic wall-derived cardiomyocytes. This AoC subpopulation delivered also endothelial cells and macrophages with a particular accumulation within the aortic wall-derived cardiomyocyte containing colonies. In vivo, cardiomyocyte differentiation capacity was studied by implantation of fluorescently labeled AoCs into chick embryonic heart. These cells acquired cardiomyocyte-like phenotype as shown by αSRA (α-sarcomeric actinin) expression. Furthermore, coronary adventitial Flk1 + and CD34 + cells proliferated, migrated into the myocardium after mouse myocardial infarction, and expressed Isl-1 + (insulin gene enhancer protein-1) indicative of cardiovascular progenitor potential. Conclusions: Our data suggest Flk1 + CD34 + vascular adventitia-resident stem cells, including those of coronary adventitia, as a novel endogenous source for generating cardiomyocytes. This process is essentially supported by endothelial cells and macrophages. In summary, the therapeutic manipulation of coronary adventitia-resident cardiac stem and their supportive cells may open new avenues for promoting cardiac regeneration and repair after myocardial infarction and for preventing heart failure.

Abstract P394: Angiotensin-(1-7) Attenuates Diastolic Dysfunction And Cardiac Remodeling In Murine Model Of Heart Failure With Preserved Ejection Fraction

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Pariya Edalat ◽  
Karina Gomes ◽  
Noura N Ballasy ◽  
Anshul S Jadli ◽  
Darrell D Belke ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Hypertrophy ◽  
Diastolic Dysfunction ◽  
Murine Model ◽  
Cardiac Remodeling ◽  
Control Group ◽  
Chow Diet ◽  
Preserved Ejection Fraction ◽  
Phosphorylation Level

Background: Heart failure with preserved ejection fraction (HFpEF) is a global public health epidemic that accounts for half of the heart failure cases. Various therapeutic approaches have been tested to block the activation of the Renin-Angiotensin System (RAS), including AT1R blockers (ARBs), Angiotensin-Converting Enzyme (ACE) inhibitors (ACEi), and direct renin inhibitors (DRIs) with modest to negligible benefits. The discovery of ACE2, a novel homolog of ACE, has advanced our understanding of the RAS. ACE2 is a monocarboxypeptidase that degrades Ang II into Ang-(1-7), which works via the activation of the Mas receptor. It has been well understood that the actions of Ang-(1-7) attenuate cardiac remodeling, production of ROS, and cardiac fibrosis. Objective: To determine the therapeutic role of Ang-(1-7) in HFpEF and identify the molecular mechanism related to its action. Methods and Results: To generate a murine model of HFpEF, male WT mice (n=24) were subjected to HFD in addition to eNOS inhibition with L-NAME (0.5 g l-1 in drinking water), as previously described. The control group (n=12) received chow diet and normal tap water. The murine model of HFpEF was validated using the non-invasive transthoracic echocardiography and invasive pressure-volume (PV) loop analyses, which exhibited diastolic dysfunction as well as cardiac hypertrophy. To evaluate the effects of Ang-(1-7) on HFpEF, animals were administered with either saline (n=12) or Ang-(1-7) (n=12) (24 μg/kg/day) for four weeks. Ang-(1-7) treatment improved diastolic function by reducing LVEDP (Ctrl: 8.267±1.254; HFD+L-NAME: 17.64±1.925; Ang-(1-7): 9.100±1.578) and Tau value (Ctrl: 7.365±0.5752; HFD+L-NAME: 9.224±0.3569; Ang-(1-7): 7.381±0.3041). Furthermore, Ang-(1-7) reduced cardiac hypertrophy by reducing the phosphorylation level of MAPK ERK 1/2 (Ctrl: 0.9074±0.1088; HFD+L-NAME: 1.212±0.1369; Ang-(1-7): 0.5615±0.1502) and increasing the phosphorylation level of AMPK (Ctrl: 0.1502±0.1502; HFD+L-NAME: 0.6127±0.06414; Ang-(1-7): 0.7852±0.1006). Ang-(1-7) treatment also reduces cardiomyocytes’ size and decreases interstitial fibrosis, as indicated by WGA and PSR staining. Conclusion: Ang-(1-7) treatment attenuated the development of HFD+L-NAME-induced HFpEF, reduced cardiac hypertrophy, and improved metabolic function.

Abstract 17371: In-Hospital Outcomes of Ablation for Ventricular Tachycardia in Heart Failure With Reduced Ejection Fraction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Raj Patel ◽  
Dipesh Ludhwani ◽  
Harsh P Patel ◽  
Samarthkumar J Thakkar ◽  
Love shah ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ventricular Tachycardia ◽  
Catheter Ablation ◽  
Ejection Fraction ◽  
Reference Group ◽  
Coronary Bypass ◽  
Reference Population ◽  
Reduced Ejection Fraction ◽  
Vt Ablation

Introduction: Ventricular tachycardia (VT) is a significant cause of morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF). Hypothesis: Data on efficacy, safety, and outcomes of catheter ablation for VT in HFrEF have not been studied well. Methods: The 2002-2014 Nationwide Inpatient Sample (NIS) was used to identify all hospitalizations with a principle diagnosis of VT (International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] code 427.1) and a secondary diagnosis of HFrEF. Patients who underwent catheter ablation were identified using ICD-9-CM procedure code 37.34. Results: Of 228,557 patients with HFrEF & VT, 5845 (2.56%) underwent catheter ablation. The prevalence of Diabetes Mellitus (DM) and Chronic Kidney disease (CKD) was higher in the reference population contrary to a higher prevalence of prior myocardial infarction (MI), coronary bypass and AICD in those undergoing CA. The frequency of complications in the ablation group was 19.47%, the most common being post-operative hemorrhage (8.3%). This was followed by myocardial infarction (5.34%), pericardial complications (3.38%), and neurological complications (2.14%) (Figure 1.). The odds of in-hospital mortality were lower in the CA group compared to the reference group (5.08% vs 9.42%, p<0.05). Conclusions: Compared to medical therapy, VT ablation in HFrEF is associated with lower mortality though with significant complication rate. This suggests a need for future studies identifying the safety measures in VT ablations and instituting appropriate interventions to improve overall VT ablation outcomes.

Abstract MP153: TET2 Regulates Type I Interferon Signaling in the Hematopoietic Response to Myocardial Infarction

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Claire Zhang ◽  
David M Calcagno ◽  
Avinash Toomu ◽  
Kenneth M Huang ◽  
Zhenxing Fu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Bone Marrow ◽  
Cardiac Remodeling ◽  
Type I Interferon ◽  
Myeloid Cells ◽  
Type I ◽  
Type I Ifn ◽  
Clonal Hematopoiesis ◽  
Hematopoietic Response

Myocardial infarction (MI) elicits a rapid and vigorous reaction from the bone marrow hematopoietic compartment, inducing a massive efflux of myeloid first responders into the bloodstream. These cells traffic to the infarct, where they mediate cardiac remodeling and repair through inflammatory signaling and recruitment of additional immune cells to the injured myocardium. A hyperinflammatory myeloid compartment, as is produced by mutations in epigenetic regulator TET2 associated with clonal hematopoiesis, can thus drive adverse cardiac remodeling after MI and accelerate progression to heart failure. Whether loss of TET2 alters the transcriptional landscape of MI-induced myelopoiesis remains to be investigated in an unbiased fashion. Here, we performed single-cell RNA sequencing of >16,000 bone marrow myeloid cells isolated from wild-type and Tet2 -/- mice after MI to characterize the emergency hematopoietic response in the presence and absence of TET2. Our data capture distinct transitional states of myeloid lineage commitment and maturation, originating from myeloid progenitors and progressing along divergent granulocytic and monocytic differentiation trajectories. Additionally, we delineate a subpopulation of interferon (IFN)-activated myeloid progenitors, monocytes, and neutrophils characterized by the concerted upregulation of various Type I IFN-stimulated genes, and find the fraction of IFN-activated cells, as well as the degree of activation, to be markedly higher in Tet2 -/- mice. We have previously described activation of this pathway after MI in mice, and demonstrated cardioprotective effects of its genetic or pharmacological inhibition. Our findings reveal heightened activation of the antiviral Type I interferon response among bone marrow myeloid cells of Tet2 -/- mice during MI-induced emergency hematopoiesis. This highlights IFN signaling as a potential candidate driver of cardiovascular pathologies (including atherosclerosis, myocardial infarction, and heart failure) associated with TET2-mediated clonal hematopoiesis. Further studies are necessary to investigate whether Tet2 -/- mice exhibit enhanced response to blockade of Type I IFN signaling after MI, and to determine whether myeloid cells of TET2 -mutant humans are similarly activated.

scholarly journals P738 Association of galectin-3 and soluble ST2, and their changes, with echocardiographic parameters and development of heart failure after ST-segment elevation myocardial infarction

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A Tyminska ◽  
A Kaplon-Cieslicka ◽  
K Ozieranski ◽  
M Budnik ◽  
A Wancerz ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ejection Fraction ◽  
St Segment Elevation ◽  
St Segment ◽  
Lv Mass ◽  
Galectin 3 ◽  
Echocardiographic Parameters ◽  
One Year

Abstract Background The occurrence of HF (heart failure) with preserved ejection fraction (HFpEF) has risen significantly over the past decade. Galectin-3 (Gal-3) and soluble ST2 (sST2) are involved in inflammatory processes and fibrosis and might be useful in estimation of the risk of HFpEF development after myocardial infarction (MI).Purpose: To investigate the association of Gal-3 and sST2, and their follow-up changeswith echocardiographic parameters of systolic and diastolic dysfunctionin patients (pts) with ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention (pPCI). Methods:A prospective, observational study, BIOSTRAT (NCT03735719), enrolled 117 pts. Gal-3 and sST2 serum collection and echocardiography were performed twice (during index hospitalization and on a control visit at one-year follow-up). Assessedat baseline and at one-year echocardiographic indices included left ventricular ejection fraction (LVEF), atrial and ventricular size, LV posterior wall and septal thickness, LV hypertrophy based on LV mass index, mitral inflow velocities, and early diastolic tissue velocities at the lateral and medial mitral annulus. Results:Mean baseline concentrations of Gal-3 and sST2 (7.5 and 26.4 ng/mL, respectively) were increased at one-year follow-up (8.5 ng/mL, p &lt; 0.001 and 31.4 ng/mL, p = 0.001, respectively). Fifty of 105 pts (48%) developed HF and 30% of the study population had LVEF &lt;50% at one-year. There were no significant differences between pts with LVEF &lt;50% and ≥50% in terms of baseline, follow-up, nor changes in Gal-3 and sST2 concentrations from baseline to the one-year visit. Gal-3 and sST2 concentrations at baseline, after one-year, and their changes were correlated with echocardiographic parameters. Correlation analysis revealed that higher baseline Gal-3 concentrations correlated inversely only with LV end-diastolic volume at one-year. There were no other significant correlations of baseline, follow-up, nor changes in Gal-3 concentration with echocardiographic parameters. Baseline sST2 values correlated positively with LV end-diastolic diameter, LV end-systolic volume, LV mass index, and inversely with LVEF at one-year, but not with baseline echocardiographic parameters. Changes in sST2 concentration correlated positively only with LVEF at one-year. There were no significant correlations of sST2 concentrations at follow-up with echocardiographic parameters. Only pts with a higher sST2 baseline level had lower LVEF at baseline and after one-year, and pts with higher concentrations of both Gal-3 and sST2 at baseline were more likely to have LV hypertrophy initially and after one-year. There was no clear association of rising biomarkers’ quartiles with other echocardiographic parameters. Conclusions:There was no clear association between both biomarkers and echocardiographic parametersof diastolic dysfunction. Increasing levels of Gal-3 and sST2 do not reflect the HFpEF development in pts after STEMI.

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