angiogenin and Myocardial-Infarction

Left ventricular (LV) systolic function is a significant prognostic factor in patients after myocardial infarction (MI). Multiple angiogenic and inflammatory factors are involved in postinfarction LV remodelling process. In addition, CD34+progenitor cells mobilised from bone marrow and tissue niches participate in regeneration of the infarcted myocardium.. To examine relationships between LV ejection fraction (LVEF) and wall motion score index (WMSI) and the number of CD34+ cells and plasma levels of vascular endothelial growth factor (VEGF), angiogenin and such inflammatory factors as interleukin 6 (IL-6), interleukin 8 (IL-8), and high-sensitivity C-reactive protein (hsCRP) in patients with ST-elevation MI (STEMI).. The study group included 61 patients with STEMI treated with primary percutaneous coronary intervention (PCI)involving bare metal stent implantation. Plasma levels of the evaluated angiogenic and inflammatory factors were measured by flow cytometry at 4 time points (just before PCI, 24 h later, at hospital discharge, and 30 days after STEMI). LVEF and WMSI were measured by echocardiography at hospital discharge, 1 month later, and 6 months later. We compared angiogenic and inflammatory factor levels in patients with no improvement of the LV systolic function during the follow-up (group 1, n = 22)vs. those with improved LV systolic function (group 2, n = 39).. No differences in the levels of VEGF, angiogenin, IL-6, IL-8, and hsCRP, and the number of CD34+ cells were observed between the two groups. Despite this, we found significant negative correlations between hsCRP level and LVEF,and positive correlations between hsCRP level and WMSI in both patient groups, but these correlations were much stronger in group 1. We also found a significant negative correlation between WMSI at 6 months and the number of CD34+ cells measured 24 h after PCI.. 1. Evaluation of plasma VEGF, angiogenin, IL-6, IL-8, and hsCRP levels and the number of CD34+ cells at different time points in patients with STEMI did not allow predicting the direction of changes in LVEF and WMSI. 2. Observed significant correlations between hsCRP level and LVEF and WMSI may suggest a harmful effect of inflammation on postinfarction myocardial remodelling. 3. A significant negative correlation between the number of CD34+ and WMSI suggests that increased mobilisation of these cells might have a beneficial effect on systolic function after MI.

Topics: Antigens, CD34; C-Reactive Protein; Female; Follow-Up Studies; Hematopoietic Stem Cell Mobilization; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Ribonuclease, Pancreatic; Stroke Volume; Ultrasonography; Vascular Endothelial Growth Factor A

Although stem cell-derived exosomes have been recognized as new candidates for cell-free treatment in myocardial infarction (MI), the challenge to improve the exosome retention in ischemic tissue remains. Our previous research indicated that islet-1(ISL1) overexpression enhances the paracrine function of mesenchymal stem cells (MSCs) and promotes angiogenesis in a model of MI. In this study, genetically engineered ISL1-MSC-derived exosomes (ISL1-MSCs-Exo) were collected, and the contents were analyzed by exosomal RNA sequencing. Next, we investigated if ISL1-MSCs-Exo could exert therapeutic effects and their incorporation into a new angiogenin-1 hydrogel (Ang-1 gel) could boost the retention of exosomes and further enhance their protective effects. Our results demonstrated that ISL1-MSCs-Exo could play a therapeutic role in vitro and in vivo, which might be due to changed exosomal contents. Ang-1 gel increased the retention and enhanced the anti-apoptosis, proliferation, and angiogenic capacity of ISL1-MSCs-Exo in endothelial cells. Echocardiography revealed that Ang-1 gel significantly augment the therapeutic effects of ISL1-MSCs-Exo for MI. The main mechanism might result from increased retention of ISL1-MSCs-Exo, herein enhanced pro-angiogenetic effects in an ischemic heart. Taken together, our findings indicated that ISL1-MSCs-Exo had endothelium-protective and pro-angiogenic abilities alone and Ang-1 gel could notably retain ISL1-MSCs-Exo at ischemic sites, which improved the survival and angiogenesis of endothelial cells and accelerated the recovery of MI. These results not only shed light on the therapeutic mechanism of ISL1-MSCs-Exo incorporated with Ang-1 gel but also offer a promising therapeutic option for ischemic disease.

Topics: Endothelial Cells; Exosomes; Humans; Hydrogels; Mesenchymal Stem Cells; Myocardial Infarction; Neovascularization, Pathologic; Ribonuclease, Pancreatic

This study aimed to develop a gene delivery system using ultrasound-targeted microbubbles destruction (UTMD) combined with nuclear localization signal (NLS) and investigate its efficacy and safety for therapeutic angiogenesis in canine myocardial infarction (MI) model.. Fifty MI dogs were randomly divided into 5 groups and transfected with Ang-1 gene plasmid: (i) group A: only injection of microbubbles and Ang-1 plasmid; (ii) group B: only UTMD mediated gene transfection; (iii) group C: UTMD combined with classical NLS mediated gene transfection; (iv) group D: UTMD combined with mutational NLS mediated transfection; and (v) group E: UTMD combined with classical NLS in the presence of a nucleus transport blocker. The mRNA and protein expression of Ang-1 gene, microvessel density (MVD) cardiac troponin I (cTnI), and cardiac function were determined after transfection.. The expression of mRNA and protein of Ang-1 gene in group C was significantly higher than that of the other groups (all. The gene delivery system composed of UTMD and NLS is efficient and safe.

Topics: Animals; Dog Diseases; Dogs; Gene Expression Regulation; Gene Transfer Techniques; Microbubbles; Myocardial Infarction; Ribonuclease, Pancreatic; RNA, Messenger; Troponin I; Ultrasonic Waves

An inflammatory response plays a crucial role in myocardial damage after an acute myocardial infarction.. To measure serum concentrations of several mediators in patients with an acute myocardial infarction (STEMI) and to assess their potential relationship with a risk of coronary instability.. The 33 patients with STEMI and 19 healthy volunteers were analyzed. The clinical data were obtained; as well serum concentrations of tryptase, endothelin (ET-1), angiogenin, soluble c-kit, and PDGF were measured.. Patients with STEMI had higher serum tryptase and ET-1 than healthy volunteers (2,5 ± 0,4 ng/mL versus 1,1 ± 0,4 ng/mL and 0,7 ± 0,1 ng/mL versus 0,3 ± 0,1 ng/mL, resp.). Subjects with significant lesion in left anterior descending artery (LAD) had lower serum ET-1 compared to those with normal LAD (0,6 ± 0,2 pg/mL versus 0,9 ± 0,4 pg/mL). Patients with three-vessel coronary artery disease (CAD) had higher level of soluble c-kit compared to those with one- or two-vessel CAD: 19,9 ± 24,1 ng/mL versus 5,6 ± 1,9 ng/mL.. Elevated serum tryptase and ET-1 may be markers of increased coronary instability; some cytokines may be related to the extension of CAD.

Topics: Aged; Endothelins; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet-Derived Growth Factor; Prospective Studies; Proto-Oncogene Proteins c-kit; Ribonuclease, Pancreatic; Tryptases

Previous studies have demonstrated that biological aging has a negative influence on the therapeutic effects of mesenchymal stem cells (MSCs)-based therapy. Using a rat myocardial infarction (MI) model, we tested the hypothesis that silent mating type information regulation 2 homolog 1 (SIRT1) may ameliorate the phenotype and improve the function of aged MSCs and thus enhance the efficacy of aged MSCs-based therapy.. Sixty female rats underwent left anterior descending coronary artery ligation and were randomly assigned to receiving: intramyocardial injection of cell culture medium (DMEM group); SIRT1 overexpression vector-treated aged MSCs (SIRT1-aged MSCs group) obtained from aged male SD rats or empty vector-treated aged MSCs (vector-aged MSCs group). Another 20 sham-operated rats that underwent open-chest surgery without coronary ligation or any other intervention served as controls.. SIRT1-aged MSC group exhibited enhanced blood vessel density in the border zone of MI hearts, which was associated with reduced cardiac remodeling, leading to improved cardiac performance. Consistent with the in vivo data, our in vitro experiments also demonstrated that SIRT1 overexpression ameliorated aged MSCs senescent phenotype and recapitulated the pro-angiogenesis property of MSCs and conferred the anti-stress response capabilities, as indicated by increases in pro-angiogenic factors, angiopoietin 1 (Ang1) and basic fibroblast growth factor (bFGF), expressions and a decrease in anti-angiogenic factor thrombospondin-1 (TBS1) at mRNA levels, and increases in Bcl-2/Bax ratio at protein level.. Up-regulating SIRT1 expression could enhance the efficacy of aged MSCs-based therapy for MI as it relates to the amelioration of senescent phenotype and hence improved biological function of aged MSCs.

Topics: Animals; Biomarkers; Cell- and Tissue-Based Therapy; Cells, Cultured; Cellular Senescence; Disease Models, Animal; Echocardiography; Female; Fibroblast Growth Factor 2; Heart; Hemodynamics; Male; Mesenchymal Stem Cell Transplantation; Myocardial Infarction; Phenotype; Rats; Rats, Sprague-Dawley; Ribonuclease, Pancreatic; Sirtuin 1; Treatment Outcome; Up-Regulation

To examine the effects of angiogenin modified mesenchymal stem cells (MSCs) on ventricular remodeling and cardiac function in a rat model of acute myocardial infarction.. MSCs were transfected with adenoviral vectors carrying either angiogenin (MSC(AdANG)) or EGFP (MSC(AdEGFP)). Angiogenin gene amplification, protein expression and cell death were assayed after hypoxic treatment. DiI labeled MSC(AdANG) and MSC(AdEGFP) were injected into infracted heart. Six weeks after cell transplantation, echocardiography and histological study were performed.. After hypoxia treatment, angiogenin modified MSCs effectively expressed angiogenin for at least 14 days. The death of MSC(AdANG) was one-third of MSCAd(EGFP), and 50% of untreated MSCs. In the infracted myocardium, the number of DiI labeling cells in MSC(AdANG) group with high angiogenin expression was three-fold that in MSC(AdEGFP) group. Echocardiograms suggested that angiogenin modified MSCs significantly improved left ventricular (LV) systolic and diastolic function. Histological study confirmed that ventricular remodeling was attenuated significantly in MSC(AdANG) group. Furthermore, vasculogenesis was enhanced significantly in MSC(AdANG) group as measured by both factor VIII and alpha-SMA staining.. Angiogenin modified MSCs enhanced the tolerance of engrafted MSCs to hypoxia injury in vitro and improved their viability in infracted hearts, thus helping preserve the LV contractile function and attenuate LV remodeling through vasculogenesis.

Topics: Actins; Adenoviridae; Angiogenic Proteins; Animals; Antigens, CD; Capillaries; Cell Hypoxia; Cell Survival; Collagen; Gene Expression; Genetic Vectors; HLA-DR Antigens; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Myocardial Infarction; Myocardium; Neovascularization, Physiologic; Rats; Rats, Inbred Lew; Ribonuclease, Pancreatic; Transfection; Ventricular Function, Left; Ventricular Remodeling; Vimentin

In vitro studies have demonstrated that bovine angiogenin (ANG) significantly stimulates both the migration of endothelial cells and the formation of tubelike structures. The aim of this study was to explore whether ANG gene transfer could enhance vascularization, modify left ventricular remodeling, and attenuate cardiac dysfunction in rats with myocardial infarction (MI). We constructed a recombinant adeno-associated virus vector encoding the ANG gene (rAAV-ANG) and evaluated its angiogenic potential after regional transfection by intramyocardial injection immediately after left anterior descending artery ligation in rats. Four weeks after coronary artery ligation, rAAV-ANG transfection upregulated the myocardium ANG protein expression level in both normal and MI rats, and immunohistochemistry showed that the overexpressed ANG was distributed in the cytoplasm of cardiomyocytes. In rats with MI, rAAV-ANG treatment altered left ventricular remodeling, as indicated by a decrease in left ventricular end diastolic diameter, left ventricular end systolic diameter, cardiomyocyte diameter, ventricular weight to body weight ratio and interstitial fibrosis infiltration. We also found an increase in capillary density and partly restored cardiac function in the group receiving rAAV-ANG treatment. These results confirmed that in rats with MI, ANG gene transfer could induce angiogenesis, alter left ventricular remodeling, and attenuate cardiac dysfunction. This study provides a new choice of treatment for ischemic heart disease.

Topics: Animals; Cattle; Dependovirus; Echocardiography; Gene Expression; Gene Transfer Techniques; Genes, Reporter; Genetic Vectors; Immunohistochemistry; Male; Myocardial Infarction; Neovascularization, Physiologic; Rats; Rats, Wistar; Ribonuclease, Pancreatic; Survival Analysis; Transfection; Ventricular Remodeling