Inflammation Related lncNOS2P3-miR-939-5p-iNOS/TNFα Pathway Inhibits Myocardial and Endothelial Cells Apoptosis in Chronic Heart Failure

2019 ◽  
Author(s):  
Cuncun Chen ◽  
Ming Zong ◽  
Ying Lu ◽  
Yide Guo ◽  
Honggen Lv ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Chronic Heart Failure

scholarly journals Pharmacological evidence: a new therapeutic approach to the treatment of chronic heart failure through SUR2B/Kir6.1 channel in endothelial cells

2016 ◽  
Vol 38 (1) ◽  
pp. 41-55 ◽  
Author(s):  
Shang Wang ◽  
Chao-liang Long ◽  
Jun Chen ◽  
Wen-yu Cui ◽  
Yan-fang Zhang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Chronic Heart Failure ◽  
Therapeutic Approach

Oxidative stress induces myeloperoxidase expression in endocardial endothelial cells from patients with chronic heart failure

2008 ◽  
Vol 104 (3) ◽  
pp. 307-320 ◽  
Author(s):  
Giampiero Rocca ◽  
Antonino Stefano ◽  
Ermanno Eleuteri ◽  
Rita Anzalone ◽  
Francesca Magno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Endothelial Cells ◽  
Chronic Heart Failure ◽  
Endocardial Endothelial Cells

scholarly journals Indexes of Angiogenic Activation in Myocardial Samples of Patients with Advanced Chronic Heart Failure

Medicina ◽  
2019 ◽  
Vol 55 (12) ◽  
pp. 766
Author(s):  
Klara Komici ◽  
Isabella Gnemmi ◽  
Claudia Sangiorgi ◽  
Fabio Luigi Massimo Ricciardolo ◽  
Mauro Rinaldi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Chronic Heart Failure ◽  
Cardiac Fibrosis ◽  
Heart Tissue ◽  
Experimental Models ◽  
Left Ventricular ◽  
Tissue Samples ◽  
Small Series ◽  
Angiopoietin 1

Background and objectives: Ischemic and idiopathic heart failure are characterized by reactive cardiac fibrosis and impaired vasculogenesis involving pro-angiogenic factors such as angiogenin, angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2), as demonstrated in experimental models of heart failure. However, differences in the molecular pathways between these cardiomyopathies are still unclear. In this short communication, we evaluate and compare the expression of pro-angiogenic molecules in the heart tissue of patients with advanced chronic heart failure (CHF) of ischemic vs. nonischemic etiology. Materials and Methods: We obtained heart tissue at transplantation from left ventricular walls of 16 explanted native hearts affected by either ischemic (ICM) or nonischemic dilated cardiomyopathy (NIDCM). Tissue samples were examined using immunohistochemistry for angiogenic molecules. Results: We found immunopositivity (I-pos) for angiopoietin-1 mainly in the cardiomyocytes, while we observed I-pos for Ang-2 and Tie-2 receptor mainly in endothelial cells. Expression of Procollagen-I (PICP), angiogenin, Ang-1, and Tie-2 receptor was similar in ICM and NIDCM. In contrast, endothelial immunopositivity for Ang-2 was higher in ICM samples than NIDCM (p = 0.03). Conclusions: In our series of CHF heart samples, distribution of Ang-1 and angiogenin was higher in cardiomyocytes while that of Ang-2 was higher in endothelial cells; moreover, Ang-2 expression was higher in ICS than NIDCM. Despite the small series examined, these findings suggest different patterns of angiogenic stimulation in ICM and NIDCM, or at least a more altered endothelial integrity in ICD. Our data may contribute to a better understanding of the angiogenesis signaling pathways in CHF. Further studies should investigate differences in the biochemical processes leading to heart failure.

scholarly journals Differentially expressed lnc - NOS2P3-miR-939-5p  axis in chronic heart failure inhibits myocardial and endothelial cells  apoptosis via iNOS/TNFα pathway

2020 ◽  
Author(s):  
Cuncun Chen ◽  
Ming Zong ◽  
Ying Lu ◽  
Yide Guo ◽  
Honggen Lv ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Chronic Heart Failure ◽  
Inflammatory Cytokines ◽  
Target Genes ◽  
Elevated Serum ◽  
Luciferase Reporter ◽  
Induced Apoptosis ◽  
And Control ◽  
Level Analysis

Abstract Background: Inflammatory cytokines induced cells apoptosis is important for initiation and progression of chronic heart failure (CHF). Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) were critical in this pathogenesis. However, their roles in inflammation and apoptosis of CHF remain unclear. Methods: A total of 75 CHF and 36 non-CHF control patients were collected and the level of miR-939-5p was detected. Bioinformatics analysis and luciferase reporter assay was used to predict and verify pairs of lncRNA-miRNA-mRNA. RT-qPCR was used to evaluate the expression of lncRNA, miRNAs and mRNAs. CCK8 and flow cytometry were applied to determine cells vitality and apoptosis. Western blot was used for protein level analysis. Results : CHF patients had elevated serum miR-939-5p, with greater increase in NYHA I-II patients than in NYHA III-IV. Moreover, miR-939-5p was positively correlated with BNP in NYHA III-IV patients, while not in NYHA I-II, suggesting that miR-939-5p might be an additional supplement for diagnosis of heart failure. Further study showed miR-939-5p mimic promoted proliferation and inhibited inflammatory cytokines induced apoptosis of HUVECs and H9C2, while inhibition of endogenous miR-939-5p by antagomir produced the opposite effects. INOS and TNFα were identified and confirmed as target genes of miR-939-5p. Moreover, we identified lncRNA-NOS2P3 as a sponge RNA to inhibit miR-939-5p expression, regulate the expression of iNOS/TNFα, and control inflammation induced myocardial and endothelial cells apoptosis. Conclusions : Together, CHF patients exhibited elevated serum miR-939-5p especially in NYHA I-II grades. Lnc-NOS2P3-miR-939-5p-iNOS/TNFα pathway played an important role in regulating inflammatory cytokines induced cells apoptosis and provided a promising strategy for diagnosis and treatment of CHF.

scholarly journals Indexes of Angiogenic Activation in Myocardial Samples of Patients with Advanced Chronic Heart Failure

2019 ◽  
Author(s):  
Klara Komici ◽  
Isabella Gnemmi ◽  
Claudia Sangiorgi ◽  
Fabio Luigi Massimo Ricciardolo ◽  
Mauro Rinaldi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Chronic Heart Failure ◽  
Cardiac Fibrosis ◽  
Heart Tissue ◽  
Experimental Models ◽  
Left Ventricular ◽  
Tissue Samples ◽  
Idiopathic Cardiomyopathy ◽  
Angiopoietin 2

Background and Objectives: Ischemic and idiopathic heart failure are two different etiologies, however reactive cardiac fibrosis together with impaired vasculogenesis has been described in both of them. Implication of main proangiogenic factors as: angiogenin, agiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) has been described mainly in experimental models of heart failure. However, differences in molecular pathways between these cardiomyopathies are still under investigation. In this short communication we aimed to evaluate and compare the expression of pro-angiogenic molecules in the heart tissue of patients with advanced chronic heart failure (CHF) of ischemic and idiopathic etiology. Methods and Results: Heart tissue from left ventricular walls was obtained at transplantation from ischemic heart disease (IHD), idiopathic cardiomyopathy (ICM) patients. Tissue samples were examined using immunohistochemistry for angiogenic molecules. Immunopositivity (I-pos) for angiopoietin-1 was mainly observed in the cardiomyocytes, while I-pos for Ang-2 and Tie-2 receptor mainly in endothelial cells. Procollagen-I (PICP), angiogenin, Ang-1, Tie-2 receptor, were similarly expressed in IHD and ICM patients. In contrast, endothelial immunopositivity for Ang-2 was higher in IHD samples compared to ICM (p=0.03). Conclusions: Ang-2 expression is different in heart tissue of ICM and ICM patients and distribution of Ang-1 and angiogenin is higher in cardiomyocytes, whereas Ang-2 higher in endothelial cells, suggesting a different pattern of angiogenic stimulation, or at least of altered endothelial integrity. This data may serve for further studies investigating angiogenesis signaling pathways and in HF of different etiology.

Myocardial infarction triggers Inflammatory deterioration of vascular niche by accelerating loss of a specific vessel subtype in bone

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Hoffmann ◽  
G Luxan ◽  
W.T Abplanalp ◽  
T Rasper ◽  
A.M Fischer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Chronic Heart Failure ◽  
Ischemic Heart Disease ◽  
Ischemic Heart ◽  
Vessel Length ◽  
Vascular Niche ◽  
The Impact

Abstract Introduction The interface between heart and bone emerges as a key trigger of post-infarction inflammation and progression of chronic heart failure (CHF). However, our knowledge on the underlying mechanisms of this interaction is incomplete. Bone vasculature, specifically so-called H-type (Endomucinhigh) endothelial cells (EC), plays a crucial role in maintenance of the bone integrity and regulation of hematopoietic stem cells (HSC). While previous studies in mice showed the reduction of H-type vessels by aging, the impact of ischemic heart disease is unclear. Therefore, we aimed to investigate the effects of myocardial infarction (MI) and chronic heart failure on the vascular bone cell composition in mice and humans. Methods and results Flow cytometric analysis of harvested bones at the different timepoints after MI induction in mice revealed a gradual loss of H-type endothelial cells in the time-course of developing chronic heart failure (P<0.05 at day 7 and 14 vs. control; P<0.0001 at day 28 vs. control). This results were confirmed in immunostainings of tibia sections showing a significant decrease of H-type vessel length after MI (p<0.05 at day 14 and 28, accordingly). The loss of type-H endothelium was accompanied by a significant expansion of long-term HSC in the bone (P=0.0005 at day 28 post MI vs. control). Importantly, type H ECs were also significantly reduced in the bone of ischemic post-infarct HF patients (n=16) compared with control subjects (n=8; P=0.0003). To gain insights into the mechanisms underlying the changes in the vascular niche, we performed single cells RNA sequencing of human BM ECs. These studies confirmed the decrease in Emcnexpressing ECs in ischemic HF patients, which was accompanied by significantly increased expression of inflammatory genes, including IL1b (P<0.0001). Inflammatory EC phenotypes and IL1b expression in HF could be further confirmed at protein level using cytospin immunostainings. Murine studies further revealed an early induction IL-1b specifically in H-type vessels already at day 1 after MI induction, which preceded the loss of H-type endothelium within the following 4 weeks. By inhibiting IL-1b production using a specific Nlrp3 inflammasome inhibitor (MCC950) we could observe a partial restoration of H-type EC frequencies (P=0.033) and a significant increase in H-type vessel length (p=0.035) at day 28 day after MI. Conclusions Our data show for the first time an impact of myocardial infarction and chronic heart failure on the bone marrow vasculature. These changes seem to be strongly associated with inflammatory response in H-type vessels, which precedes its loss after MI. Specifically, the induction of the inflammatory cytokine IL1b may contribute to the disturbed phenotype. This suggest that inhibition of IL1b (e.g. by canakinumab) be used as a novel strategy to prevent or reverse the deterioration of the vascular bone function in ischemic heart disease. Funding Acknowledgement Type of funding source: None

scholarly journals Impact of Rosuvastatin Treatment on HDL-Induced PKC-βII and eNOS Phosphorylation in Endothelial Cells and Its Relation to Flow-Mediated Dilatation in Patients with Chronic Heart Failure

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Ephraim B. Winzer ◽  
Pauline Gaida ◽  
Robert Höllriegel ◽  
Tina Fischer ◽  
Axel Linke ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Chronic Heart Failure ◽  
Endothelial Function ◽  
No Production ◽  
Treatment Cessation ◽  
Aortic Endothelial Cells ◽  
Enos Phosphorylation ◽  
Flow Mediated Dilatation ◽  
The Impact

Background. Endothelial function is impaired in chronic heart failure (CHF). Statins upregulate endothelial NO synthase (eNOS) and improve endothelial function. Recent studies demonstrated that HDL stimulates NO production due to eNOS phosphorylation at Ser1177, dephosphorylation at Thr495, and diminished phosphorylation of PKC-βII at Ser660. The aim of this study was to elucidate the impact of rosuvastatin on HDL mediated eNOS and PKC-βII phosphorylation and its relation to endothelial function.Methods. 18 CHF patients were randomized to 12 weeks of rosuvastatin or placebo. At baseline, 12 weeks, and 4 weeks after treatment cessation we determined lipid levels and isolated HDL. Human aortic endothelial cells (HAEC) were incubated with isolated HDL and phosphorylation of eNOS and PKC-βII was evaluated. Flow-mediated dilatation (FMD) was measured at the radial artery.Results. Rosuvastatin improved FMD significantly. This effect was blunted after treatment cessation. LDL plasma levels were reduced after rosuvastatin treatment whereas drug withdrawal resulted in significant increase. HDL levels remained unaffected. Incubation of HAEC with HDL had no impact on phosphorylation of eNOS or PKC-βII.Conclusion. HDL mediated eNOS and PKC-βII phosphorylation levels in endothelial cells do not change with rosuvastatin in CHF patients and do not mediate the marked improvement in endothelial function.

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