Abstract 648: Heme-oxygenase-1 Gene Expression Ameliorates Cardiac Dysfunction Following Myocardial Infarction In C57 Mice By Recruitment Of Angiogenic Factors And Angiogenesis In C57 Mice

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
David Sacerdoti ◽  
Sumit R Monu ◽  
Paola Pesce ◽  
Stephen J Peterson ◽  
Komal Sodhi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Cardiac Function ◽  
Heme Oxygenase ◽  
Angiogenic Factors ◽  
Heme Oxygenase 1 ◽  
Artery Ligation ◽  
Capillary Formation ◽  
Beneficial Effects ◽  
Angiogenic Proteins

Rational: Angiogenesis is essential in order to increase blood circulation in infarcted tissue of MI (Myocardial infarction). Increased Heme-Oxygenase (HO)-1 gene expression increases angiogenic proteins, e.g. VEGF, bFGF, EGF, angiopoietin and adiponectin. Objective: To investigate whether increased levels of HO-1, after the occurrence of a MI, improves angiogenesis and capillary formation in ischemic myocardium, thereby improving cardiac function. METHODS: Experimental MI was induced by LAD (Left anterior descending artery) ligation. C57BL6 mice were divided into 4 groups: Sham; MI; 5 days after MI treated with the HO-1 inducer, cobalt protoporphyrinIX (CoPP); and, CoPP in the presence of the HO activity inhibitor, Stannous Mesoporphyrin (SnMP). HO-1 downstream signaling proteins were determined including VEGF, CD31 and adiponectin. Echocardiography was performed weekly for 4 weeks after surgery. Results: 5 days after MI, CoPP treatment significantly increased VEGF (p<0.05 vs.MI), CD31 (p<0.05 vs.MI), and adiponectin levels (p<0.05 vs.MI). These findings were associated with a significant increase in capillary formation and blood flow in CoPP-treated animals (p<0.05 vs.MI). Echocardiography showed that left ventricle dilatation, measured as end diastolic area (EDA), was significantly reduced in CoPP- treated animals compared to MI groups (EDA: MI: 0.216±0.02cm2; MI+CoPP: 0.172±0.03 cm2; (-13%) p<0.01). This was associated with a significant decrease in apoptosis and fibrosis (P<0.05). These beneficial effects were reversed by SnMP administration. Conclusion: HO-1 improved cardiac function and enhanced angiogenesis via the recruitment of pro-angiogenic factors.

Abstract 272: RBPJ Controls the Angiogenic Response of Mouse Adult Cardiomyocytes

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Ramon Diaz Trelles ◽  
Maria Cecilia Scimia ◽  
Pilar Ruiz Lozano ◽  
Mark Mercola
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Cardiac Function ◽  
Target Genes ◽  
Notch Pathway ◽  
Oxygen Demand ◽  
Angiogenic Factors ◽  
Angiogenic Factor ◽  
Angiogenic Response ◽  
Adult Cardiomyocytes

Cardiac microvasculature density is critical for a correct cardiac function under normal and stress conditions. We found that the transcription factor RBPJ, downstream of the Notch signalling, can regulate angiogenic factors gene expression by repression (normal homeostasis) or activation (stress) and also by modulating the hypoxia induced angiogenic response. Accordingly, in normal conditions cardiomyocyte specific RBPJ KO adult mice hearts show a denser microvasculature. Isolated mouse adult cardiomyocytes show increased gene expression and promoter hyperacetylation and hypermethylation of angiogenic factors and Notch target genes (like HES1). Stress induced by myocardial infarction (MI) or cardiac overload (TAC) activate an angiogenic response to compensate the increased oxygen demand. Notch pathway is activated and RBPJ accumulated in the nucleus after MI and TAC. After TAC, deletion of RBPJ did not block hypertrophy induction, but prevented the increase in angiogenic factor production and microvessel density that normally occurs in response to increased workload. Remarkably, the KO preserved cardiac function and reduced cell death and fibrosis after myocardial infarction. Thus, RBPJ acts in cardiomyocytes as a master factor orchestrating homeostatic and disease-induced angiogenesis, and modulating RBPJ protects against ischemic injury.

Products of heme oxygenase and their potential therapeutic applications

2006 ◽  
Vol 290 (3) ◽  
pp. F563-F571 ◽  
Author(s):  
Kristin A. Kirkby ◽  
Christopher A. Adin
Keyword(s):  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Inexpensive Method ◽  
Waste Products ◽  
Biliverdin Reductase ◽  
Therapeutic Applications ◽  
Beneficial Effects ◽  
Tissue Protection ◽  
Organ Systems ◽  
Dose Dependent

Heme oxygenase 1 (HO-1) is induced in response to cellular stress and is responsible for converting the prooxidant heme molecule into equimolar quantities of biliverdin (BV), carbon monoxide (CO), and iron. BV is then converted to bilirubin (BR) by the enzyme biliverdin reductase. Experimental evidence suggests that induction of the HO system is an important endogenous mechanism for cytoprotection and that the downstream products of heme degradation, CO, BR, and BV, may mediate these powerful beneficial effects. These molecules, which were once considered to be toxic metabolic waste products, have recently been shown to have dose-dependent vasodilatory, antioxidant, and anti-inflammatory properties that are particularly desirable for tissue protection during organ transplantation. In fact, recent work has demonstrated that administration of exogenous CO, BR, or BV may offer a simple, inexpensive method to substitute for the cytoprotective effects of HO-1 in a variety of clinically applicable models. This review will attempt to summarize the relevant biochemical and cytoprotective properties of CO, BR, and BV, and will discuss emerging studies involving the therapeutic applications of these molecules in the kidney and other organ systems.

scholarly journals Garcinoic Acid Improves Cardiac Function and Enhances Angiogenesis Following Myocardial Infarction

2021 ◽  
Author(s):  
Hongyao Hu ◽  
Wei Li ◽  
Yanzhao Wei ◽  
Hui Zhao ◽  
Zhenzhong Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Vehicle Group ◽  
Potential Mechanism ◽  
Garcinia Kola ◽  
Angiogenic Proteins

Abstract Cardiac ischemia impairs angiogenesis in response to hypoxia, resulting in ventricular remodeling. Garcinoic acid (GA), the extraction from the plant garcinia kola, is validated to attenuate inflammatory response. However, the role of GA in heart failure (HF) and neovascularization after myocardial infarction (MI) is incompletely understood. The present study is striving to explore the role of GA and the potential mechanism of which in cardiac function after MI. SD rats were randomized into sham group, MI+vehicle group, and MI+GA group in vivo. Human umbilical endothelial cells (HUVECs) were cultured in vehicle or GA, and then additionally exposed to 2% hypoxia environment in vitro. MI rats displayed a dramatically reduced myocardial injury, cardiac function and vessel density in the peri-infarcted areas. GA delivery markedly improved cardiac performance and promoted angiogenesis. In addition, GA significantly enhanced tube formation in HUVECs under hypoxia condition. Furthermore, the expressions of pro-angiogenic factors HIF-1α, VEGF-A and bFGF, and pro-angiogenic proteins phospho-VEGFR2Tyr1175 and VEGFR2, as well as phosphorylation levels of Akt and eNOS were increased by GA treatment. In conclusion, GA preserved cardiac function after MI probably via promoting neovascularization. And the potential mechanism may be partially through upregulating the expressions of HIF-1α, VEGF-A, bFGF, phospho-VEGFR2Tyr1175 and VEGFR2 and activating the phosphorylations of Akt and eNOS.

Abstract 15610: The Infusion of Mesenchymal Stromal Cells Post Myocardial Infarction Increases Myocardial S100A6, Attenuates Myocyte Hypertrophy, Reduces Myocyte Apoptosis and Improves Cardiac Function

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
James Tsoporis ◽  
Shehla Izhar ◽  
Jean-Francois Desjardins ◽  
Gerald Proteau ◽  
Gustavo Yannarelli ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Fold Increase ◽  
Coronary Artery Ligation ◽  
Myocyte Hypertrophy ◽  
Beneficial Effects ◽  
Infarcted Myocardium ◽  
Donor Cells

The beneficial effects originally attributed to the ability of bone-marrow derived mesenchymal stromal cells (BM-MSCs) to differentiate into cardiomyocytes have been questioned due to the transient presence of donor cells at injury site following myocardial infarction (MI) suggesting that the MSC-induced improvement in hemodynamic function may be attributable to paracrine effects. We showed that S100A6, a 20 kDa EF-hand calcium-binding dimer, is upregulated and secreted following MI and forced expression post-MI was beneficial to the preservation of cardiac function. The aim of this study was to determine whether the beneficial effects of infused BM-MSCs may be related to the autocrine secretion of S100A6. Balb/c murine cultured green fluorescence protein (GFP)-marked BM-MSCs express S100A6 at baseline and in response to hypoxia (5%C02/95% N2) for 1 hr increase S100A6 mRNA and protein (2-3 fold, and release S100A6 (1 nM) in the culture media, responses inhibited in BM-MSCs transfected with S100A6 siRNA. Treatment of neonatal Balb/c cardiac myocytes with human recombinant S100A6 (1nM) for 1-24 hrs attenuated baseline apoptosis (30 per cent decrease in BAX/BCL2 ratio), induced cyclin-dependent kinase 1(CDK1) mRNA 1.5 fold, miR199a 2 fold and myocyte proliferation 2.5 fold, the latter inhibited by anti-miR 199a. In 12 week old Balb/c mice, saline or GFP-marked BM-MSCs transfected with either a scrambled or S100A6 siRNA were infused intravenously 3-4 hrs post coronary artery ligation. After 3-4 days the GFP-marked cells were confined to ischemic areas and represented approximately 10% of total cellularity and co-expressed collagen type IV and myosin heavy chain, characteristic of MSCs and cardiomyocytes, respectively, and were CD45(-). Despite the absence of donor cells in the infarcted myocardium 21 days after infusion, mice that have received MSCs alone compared to MSCs transfected with an S100A6 siRNA or saline alone showed a 6-fold increase in S100A6 mRNA and protein, 3-fold increase in miR199a in peri-infarcted myocardium, attenuated myocyte hypertrophy, decreased fibrosis and apoptosis, and preservation of cardiac function. In conclusion, the secretion of S100A6 by infused BM-MSCs may contribute in limiting adverse LV remodeling post-MI.

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