ResearchPad - cardiovascular-system-vascular-biology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Effect of miR-195-5p on cardiomyocyte apoptosis in rats with heart failure by regulating TGF-β1/Smad3 signaling pathway]]> https://www.researchpad.co/article/elastic_article_13841 Purpose: The present study set out to investigate the effect of miR-195-5p on cardiomyocyte apoptosis in rats with heart failure (HF) and its mechanism.

Methods: HF rat model and hypoxia/reoxygenation (H/R) cardiomyocyte model were established. miR-195-5p expression and transforming growth factor-β1 (TGF-β1)/signal transduction protein (Smad)3 signaling pathway in HF rats and H/R cardiomyocytes were interfered. miR-195-5p expression was tested by Rt-PCR, TGF-β1/Smad3 signaling pathway related proteins were detected by Western Blot, apoptosis of HF rat cardiomyocytes was tested by TUNEL, and apoptosis of cardiomyocytes induced by H/R was checked by flow cytometry.

Results: miR-195-5p was lowly expressed in myocardium of HF rats, while TGF-β1 and Smad3 proteins were high-expressed. Up-regulating miR-195-5p expression could obviously inhibit cardiomyocyte apoptosis of HF rats, improve their cardiac function, and inhibit activation of TGF-β1/Smad3 signaling pathway. Up-regulation of miR-195-5p expression or inhibition of TGF-β1/Smad3 signaling pathway could obviously inhibit H/R-induced cardiomyocyte apoptosis. Dual-luciferase reporter enzyme verified the targeted relationship between miR-195-5p and Smad3.

Conclusion: miR-195-5p can inhibit cardiomyocyte apoptosis and improve cardiac function in HF rats by regulating TGF-β1/Smad3 signaling pathway, which may be a potential target for HF therapy.

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<![CDATA[VCAM-1-targeted and PPARδ-agonist-loaded nanomicelles enhanced suppressing effects on apoptosis and migration of oxidized low-density lipoprotein-induced vascular smooth muscle cells]]> https://www.researchpad.co/article/elastic_article_13842 Purpose: Nanomicelles (NMs) have been widely used for various biomedical applications due to its unique physiochemical properties. The present study aims to investigate the effects of vascular cell adhesion molecule-1 (VCAM-1)-targeted and peroxisome proliferator-activated receptor δ (PPARδ) agonist (GW0742)-loaded NMs on apoptosis and migration in oxidized low-density lipoprotein (ox-LDL)-induced human aortic vascular smooth muscle cells (HAVSMCs).

Methods: The GW0742-loaded NMs (M-GW) and VCAM-1-targeted NMs loaded with GW0742 (TM-GW) were prepared, and then the morphologies and the size distribution of M-GM and TM-GM were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. In vitro drug release assay of M-GM and TM-GM were performed as well. Next, HAVSMCs were cultured in medium containing ox-LDL to mimic atherosclerotic environment, and the effects of free GW0742, M-GM and TM-GM on endocytosis, cell migration and apoptosis, as well as the expression of VCAM-1, and proteins associated with migration and apoptosis were measured in HAVSMCs treated with ox-LDL.

Results: M-GM and TM-GM were successfully prepared. VCAM-1 was overexpressed in HAVSMCs treated with ox-LDL, and TM-GM had a strong targeting ability to HAVSMCs treated with ox-LDL compared with M-GM. In addition, compared with free GW0742, both M-GM and TM-GM significantly diminished cell apoptosis and migration in HAVSMCs treated with ox-LDL.

Conclusions: TM-GM had a superior suppressing effect on apoptosis and migration of ox-LDL-induced HAVSMCs.

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<![CDATA[Effect of X-rays on transcript expression of rat brain microvascular endothelial cells: role of calcium signaling in X-ray-induced endothelium damage]]> https://www.researchpad.co/article/N72b39923-c2d8-4ebf-a27e-945e6e2318e0 Radiation-induced brain edema is a serious adverse effect of radiotherapy. Although there are many causes of radiation-induced brain edema, the pathogenesis is not clear and clinical treatment is not ideal. Therefore, knowing the differential expression of the brain microvascular endothelial cell (BMEC) transcriptome after brain radiotherapy may shed light on the pathogenesis of radiation-induced brain edema. The present study used RNA-Seq technique to identify 383 BMEC transcripts differentially expressed (many 2-fold or higher; P < 0.05) between control and X-ray–treated primary cultured rat BMECs. Compared with controls, X-ray–treated BMECs had 183 significantly up-regulated transcripts and 200 significantly down-regulated transcripts. The differentially expressed genes were associated with the biological processes of the cell cycle, apoptosis, vascular permeability, and extracellular junctions. The functional changes identified in the X-ray–treated BMECs included Ca2+ signaling, phosphoinositide 3-kinase–Akt signaling, and methionine degradation. These results indicated that transcript expression was substantially affected by radiation exposure and the proteins encoded by these differentially expressed genes may play a significant role in radiotherapy-induced brain edema. Our findings provide additional insight into the molecular mechanisms of radiation-induced brain edema and may be helpful in the development of clinical treatment of this adverse reaction to radiotherapy.

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<![CDATA[Sappanone A alleviates hypoxia/reoxygenation-induced cardiomyocytes injury through inhibition of mitochondrial apoptosis and activation of PI3K–Akt–Gsk-3β pathway]]> https://www.researchpad.co/article/N6dd7e059-3ecb-44b6-a063-cbcecf746dfd

Abstract

Myocardial ischemia reperfusion injury (MIRI) is a complex pathophysiological process involved with the activation of oxidative stress, inflammation and apoptosis. Sappanone A (SA), a homoisoflavanone isolated from the heartwood of Caesalpinia sappan L., could exhibit antioxidant, anti-inflammatory and anti-apoptotic activities. Therefore, we assumed that SA has a potential use for preventing against MIRI. The present study aimed to investigate the effect of SA treatment on MIRI and its mechanism. Cardiomyocytes (H9c2 cells) were treated with SA for 1 h, followed by 6 h of hypoxia/3 h of reoxygenation. Cell viability assay was detected by CCK-8 assay. Apoptosis was measured by flow cytometry and Hoechst staining. Mitochondrial permeability transition pore (mPTP) opening and mitochondrial transmembrane potential (ΔΨm) were measured by spectrophotometry and JC-1 staining. The changes of mitochondrial apoptosis-related proteins and PI3K–Akt–Gsk-3β signaling pathway were evaluated by Western blotting. The results showed that SA pretreatment enhanced the cell viability and decreased the activity of myocardial enzyme in a dose-dependent manner. Moreover, SA pretreatment significantly inhibited apoptosis, blocked mPTP opening, suppressed the release of ΔΨm, prevented the cytochrome c releasing from mitochondria into cytoplasm, and repressed the cleavage of caspase-9 and caspase-3. Furthermore, SA pretreatment increased the phosphorylation levels of Akt and Gsk-3β but not of Stat-3. Meanwhile, the protective effect of SA was abrogated by PI3K inhibitor (LY294002). In conclusion, our results demonstrate that SA could prevent hypoxia/reoxygenation-induced cardiomyocytes injury through inhibition of mitochondrial apoptosis and activation of PI3K–Akt–Gsk-3β pathway. Thus, SA may have a potential use for the prevention of MIRI.

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<![CDATA[Differential regulation of sFlt-1 splicing by U2AF65 and JMJD6 in placental-derived and endothelial cells]]> https://www.researchpad.co/article/N36b40f8f-24a9-4d5b-a798-7b60fc5e429d

Abstract

Despite years of study, the gestational disorder preeclampsia (PE) remains poorly understood. One proposed mechanism of PE development is increased soluble VEGF receptor-1 (sFlt-1), ultimately causing angiogenic imbalance and endothelial dysfunction. The soluble protein is an alternative splice variant of FLT1, which also encodes for the full-length receptor Flt-1. The mechanism of the alternative splicing, and the reason for its inappropriate increase in preeclampsia, is not well understood. U2 auxiliary factor 65 (U2AF65) and jumonji C domain-containing protein 6 (JMJD6) have been implicated in the splicing of sFlt-1. Using siRNA knockdown and plasmid overexpression in immortalized placental trophoblasts (BeWo) and primary endothelial cells (HUVECs), we examined the role these proteins play in production of sFlt-1. Our results showed that U2AF65 has little, if any, effect on sFlt-1 splicing, and JMJD6 may enhance sFlt-1 splicing, but is not necessary for splicing to occur. Utilizing a hypoxic environment to mimic conditions of the preeclamptic placenta, as well as examining placentae in the reduced uterine perfusion pressure (RUPP) model of PE, which exhibits increased circulating sFlt-1, we found increased expression of JMJD6 in both hypoxic cells and placental tissue. Additionally, we observed a potential role for U2AF65 and JMJD6 to regulate the extracellular matrix enzyme heparanase, which may be involved in the release of sFlt-1 protein from the extracellular matrix. It will be important to study the role of these proteins in different tissues in the future, as changes in expression had differential effects on sFlt-1 splicing in the different cell types studied here.

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<![CDATA[Immobilized DNA aptamers used as potent attractors for vascular endothelial cell: in vitro study of female rat]]> https://www.researchpad.co/article/N22bf139b-96b7-4760-8738-29be5d4e06b2

Abstract

Vascular endothelial cells are essential to vascular function and maintenance. Dysfunction of these cells can lead to the development of cardiovascular disease or contribute to tumorigenesis. As such, the therapeutic modulation and monitoring of vascular endothelial cells are of significant clinical interest, and several endothelial-specific ligands have been developed for drug delivery and the monitoring of endothelial function. However, the application of these ligands has been limited by their high cost and tendency to induce immune responses, highlighting a need for alternate methods of targeting vascular endothelial cells. In the present study, we explore the therapeutic potential of DNA aptamers. Using cell-SELEX technology, we identified two aptamers with specific binding affinity for vascular endothelial cells and propose that these molecules show potential for use as new ligands for drug and biomarker research concerning vascular endothelial cells.

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<![CDATA[The protective role of MiR-206 in regulating cardiomyocytes apoptosis induced by ischemic injury by targeting PTP1B]]> https://www.researchpad.co/article/N2a5c1300-bdae-4ae7-9168-9f3c7ead11a6

Abstract

MicroRNAs play essential roles in the regulation and pathophysiology of acute myocardial infarction (AMI). The purpose of the present study was to assess the expression signature of miR-206 in rat heart with AMI and the corresponding molecular mechanism. The expression of miR-206 significantly decreased in the infarcted myocardial areas and in hypoxia-induced cardiomyocytes, compared with that in the noninfarcted areas. Overexpression of miR-206 decreased cardiomyocytes apoptosis and the down-regulation of miR-206 increased cardiomyocytes apoptosis in vitro. In addition, overexpression of miR-206 in rat heart in vivo remarkably reduced myocardial infarct size and cardiomyocytes apoptosis. We identified that miR-206 had a protective effect on cardiomyocytes apoptosis with the association of its target protein tyrosine phosphatase 1B (PTP1B). Gain-of-function of miR-206 inhibited PTP1B expression and loss-of-function of miR-206 up-regulated PTP1B expression. Furthermore, overexpression of PTP1B significantly increased cardiomyocytes apoptosis. These results together suggest the protective effect of miR-206 against cardiomyocytes apoptosis induced by AMI by targeting PTP1B.

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<![CDATA[The correlation between trimethylamine N-oxide, lipoprotein ratios, and conventional lipid parameters in patients with unstable angina pectoris]]> https://www.researchpad.co/article/N5f222794-ad69-4a67-9a98-90a3ff55a412

Abstract

Purpose: Trimethylamine N-oxide (TMAO) is recently the main risk factor for coronary heart disease (CHD). Plasma lipid levels are conventionally used to predict coronary risk, but the correlation between TMAO and plasma lipid levels in unstable angina pectoris (UAP) was unclear. Our objective was to compare the plasma level of TMAO to lipoprotein ratios and conventional lipid parameters in UAP patients. Methods: A total of 114 control participants and 184 UAP patients were enrolled. Demographic characteristics were collected. Plasma levels of TMAO and lipid in all patients were measured and analyzed. The receiver operating characteristic analysis (ROC), univariate, and multivariate logistic regression analyses were carried out to examine the relationship between TMAO, lipoprotein ratios, conventional lipid parameters, and UAP. Results: The plasma levels of TMAO were remarkably increased in UAP patients (3.28 ± 1.97 µM) compared with control participants (1.52 ± 0.59 µM, P < 0.01). TMAO was significantly correlated with lipid levels in UAP patients. The ROC, univariate and multivariate logistic regression analysis both showed that the TMAO significantly increased the risk for occurrence of UAP. Conclusions: Our data indicate that the TMAO is superior to lipoprotein ratios and conventional lipid parameters in predicting occurrence of UAP.

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