Displaying all 16 publications

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  1. Priya SP, Sakinah S, Ling MP, Chee HY, Higuchi A, Hamat RA, et al.
    Acta Trop, 2017 Jul;171:213-219.
    PMID: 28427958 DOI: 10.1016/j.actatropica.2017.04.010
    Dengue virus (DENV) has emerged as a major economic concern in developing countries, with 2.5 billion people believed to be at risk. Vascular endothelial cells (ECs) lining the circulatory system from heart to end vessels perform crucial functions in the human body, by aiding gas exchange in lungs, gaseous, nutritional and its waste exchange in all tissues, including the blood brain barrier, filtration of fluid in the glomeruli, neutrophil recruitment, hormone trafficking, as well as maintenance of blood vessel tone and hemostasis. These functions can be deregulated during DENV infection. In this study, BALB/c mice infected with DENV serotype 2 were analyzed histologically for changes in major blood vessels in response to DENV infection. In the uninfected mouse model, blood vessels showed normal architecture with intact endothelial monolayer, tunica media, and tunica adventitia. In the infected mouse model, DENV distorted the endothelium lining and disturbed the smooth muscle, elastic laminae and their supporting tissues causing vascular structural disarrangement. This may explain the severe pathological illness in DENV-infected individuals. The overall DENV-induced damages on the endothelial and it's supporting tissues and the dysregulated immune reactions initiated by the host were discussed.
    Matched MeSH terms: Endothelial Cells/pathology*
  2. Sadikan MZ, Abdul Nasir NA, Lambuk L, Mohamud R, Reshidan NH, Low E, et al.
    BMC Ophthalmol, 2023 Oct 19;23(1):421.
    PMID: 37858128 DOI: 10.1186/s12886-023-03155-1
    Diabetic retinopathy (DR), one of the leading causes of visual impairment and blindness worldwide, is one of the major microvascular complications in diabetes mellitus (DM). Globally, DR prevalence among DM patients is 25%, and 6% have vision-threatening problems among them. With the higher incidence of DM globally, more DR cases are expected to be seen in the future. In order to comprehend the pathophysiological mechanism of DR in humans and discover potential novel substances for the treatment of DR, investigations are typically conducted using various experimental models. Among the experimental models, in vivo models have contributed significantly to understanding DR pathogenesis. There are several types of in vivo models for DR research, which include chemical-induced, surgical-induced, diet-induced, and genetic models. Similarly, for the in vitro models, there are several cell types that are utilised in DR research, such as retinal endothelial cells, Müller cells, and glial cells. With the advancement of DR research, it is essential to have a comprehensive update on the various experimental models utilised to mimic DR environment. This review provides the update on the in vitro, in vivo, and ex vivo models used in DR research, focusing on their features, advantages, and limitations.
    Matched MeSH terms: Endothelial Cells/pathology
  3. Khalid EB, Ayman EE, Rahman H, Abdelkarim G, Najda A
    Tumour Biol., 2016 Nov;37(11):14513-14536.
    PMID: 27651162
    The process of angiogenesis is quite well-known nowadays. Some medicines and extracts affecting this process are already used routinely in supporting the conventional treatment of many diseases that are considered angiogenic such as cancer. However, we must be aware that the area of currently used drugs of this type is much narrower than the theoretical possibilities existing in therapeutic angiogenesis. Plant substances are a large and diverse group of compounds that are found naturally in fruits, vegetables, spices, and medicinal plants. They also have different anticancer properties. The aim of this literature review article is to present the current state of knowledge concerning the molecular targets of tumor angiogenesis and the active substances (polyphenols, alkaloids, phytohormones, carbohydrates, and terpenes) derived from natural sources, whose activity against cancer angiogenesis has been confirmed.
    Matched MeSH terms: Endothelial Cells/pathology
  4. Ng CT, Yip WK, Mohtarrudin N, Seow HF
    Malays J Pathol, 2015 Dec;37(3):219-25.
    PMID: 26712666 MyJurnal
    Immortalized human endothelial cells are widely used as in vitro models for debilitating conditions such as cancer, cardiovascular and ocular diseases. Human microvascular endothelial cell (HMEC-1) is immortalized via stable transfection with a gene encoding SV40 large antigen whilst telomerase-immortalized human microvascular endothelial (TIME) cells is immortalized by engineering the human telomerase catalytic protein (hTERT) into primary microvascular endothelial cells. Here, we established a three-dimensional (3D) spheroid invasion assay with HMEC-1 and TIME and compared the difference in their ability to invade through the collagen matrix in response to exogenous growth factors, namely vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).
    Matched MeSH terms: Endothelial Cells/pathology*
  5. Devasvaran K, Tan JJ, Ng CT, Fong LY, Yong YK
    Oxid Med Cell Longev, 2019;2019:1202676.
    PMID: 31531177 DOI: 10.1155/2019/1202676
    Malaysian Tualang honey (TH) is a known therapeutic honey extracted from the honeycombs of the Tualang tree (Koompassia excelsa) and has been reported for its antioxidant, anti-inflammatory, antiproliferative, and wound healing properties. However, the possible vascular protective effect of TH against oxidative stress remains unclear. In this study, the effects of TH on hydrogen peroxide- (H2O2-) elicited vascular hyperpermeability in human umbilical vein endothelial cells (HUVECs) and Balb/c mice were evaluated. Our data showed that TH concentrations ranging from 0.01% to 1.00% showed no cytotoxic effect to HUVECs. Induction with 0.5 mM H2O2 was found to increase HUVEC permeability, but the effect was significantly reversed attenuated by TH (p < 0.05), of which the permeability with the highest inhibition peaked at 0.1%. In Balb/c mice, TH (0.5 g/kg-1.5 g/kg) significantly (p < 0.05) reduced H2O2 (0.3%)-induced albumin-bound Evans blue leak, in a dose-dependent manner. Immunofluorescence staining confirmed that TH reduced actin stress fiber formation while increasing cortical actin formation and colocalization of caveolin-1 and β-catenin in HUVECs. Signaling studies showed that HUVECs pretreated with TH significantly (p < 0.05) decreased intracellular calcium release, while sustaining the level of cAMP when challenged with H2O2. These results suggested that TH could inhibit H2O2-induced vascular hyperpermeability in vitro and in vivo by suppression of adherence junction protein redistribution via calcium and cAMP, which could have a therapeutic potential for diseases related to the increase of both oxidant and vascular permeability.
    Matched MeSH terms: Human Umbilical Vein Endothelial Cells/pathology
  6. Mohd-Ali B, Chen LY
    Cont Lens Anterior Eye, 2021 02;44(1):72-75.
    PMID: 32624364 DOI: 10.1016/j.clae.2020.06.007
    PURPOSE: To analyse and compare the alterations in corneal endothelium morphology induced by different materials and durations of wearing soft contact lenses (CL) among young adults living in Kuala Lumpur.

    METHODS: Healthy soft CL wearers were invited to participate in this study. Visual acuity (VA) was measured using the Snellen chart, and subjective refraction was performed using cross-cylinder technique. Standard ocular assessments were conducted using a slit lamp biomicroscope and morphology of corneal endothelial cells (endothelial cell density, ECD, coefficient variation, COV, hexagonality, HEX and central corneal thickness, CCT) were evaluated using a non-contact specular microscope. Statistical analysis was conducted using ANOVA and data from the right eye only is included.

    RESULTS: A total of 72 subjects (32 SiHy and 40 HCL wearers) and 24 non-CL wearers (control) participated in this study. The gender distribution for study subjects was 13 males and 59 females, with a mean age 22.15 ± 1.84 years old. The mean refraction was -1.86 ± 1.25DS. The duration of wearing CL ranged from 1 to 9 years. Subjects were later divided into 2 groups following duration of CL wear: Group 1 (<5 years) and Group 2 (≥5 years) for analysis purposes. Statistical analysis showed significant alterations in ECD, COV and HEX of CL wearers (p 

    Matched MeSH terms: Endothelial Cells/pathology
  7. Harun MSR, Marsh V, Elsaied NA, Webb KF, Elsheikha HM
    Brain Res, 2020 11 01;1746:147002.
    PMID: 32592740 DOI: 10.1016/j.brainres.2020.147002
    Toxoplasma gondii can cause parasitic encephalitis, a life-threatening infection that predominately occurs in immunocompromised individuals. T. gondii has the ability to invade the brain, but the mechanisms by which this parasite crosses the blood-brain-barrier (BBB) remain incompletely understood. The present study reports the changes associated with infection and replication of T. gondii within human brain microvascular endothelial cells (BMECs) in vitro. Our results indicated that exposure to T. gondii had an adverse impact on the function and integrity of the BMECs - through induction of cell cycle arrest, disruption of the BMEC barrier integrity, reduction of cellular viability and vitality, depolarization of the mitochondrial membrane potential, increase of the DNA fragmentation, and alteration of the expression of immune response and tight junction genes. The calcium channel/P-glycoprotein transporter inhibitor verapamil was effective in inhibiting T. gondii crossing the BMECs in a dose-dependent manner. The present study showed that T. gondii can compromise several functions of BMECs and demonstrated the ability of verapamil to inhibit T. gondii crossing of the BMECs in vitro.
    Matched MeSH terms: Endothelial Cells/pathology
  8. Safi SZ, Qvist R, Yan GO, Ismail IS
    BMC Med Genomics, 2014;7:29.
    PMID: 24885710 DOI: 10.1186/1755-8794-7-29
    Aberrant epigenetic profiles are concomitant with a spectrum of developmental defects and diseases. Role of methylation is an increasingly accepted factor in the pathophysiology of diabetes and its associated complications. This study aims to examine the correlation between oxidative stress and methylation of β1, β2 and β3-adrenergic receptors and to analyze the differential variability in the expression of these genes under hyperglycemic conditions.
    Matched MeSH terms: Endothelial Cells/pathology
  9. Wen Jun L, Pit Foong C, Abd Hamid R
    Biomed Pharmacother, 2019 Oct;118:109221.
    PMID: 31545225 DOI: 10.1016/j.biopha.2019.109221
    Ardisia crispa Thunb. A. DC. (Primulaceae) has been used extensively as folk-lore medicine in South East Asia including China and Japan to treat various inflammatory related diseases. Ardisia crispa root hexane fraction (ACRH) has been thoroughly studied by our group and it has been shown to exhibit anti-inflammatory, anti-hyperalgesic, anti-arthritic, anti-ulcer, chemoprevention and suppression against inflammation-induced angiogenesis in various animal model. Nevertheless, its effect against human endothelial cells in vitro has not been reported yet. Hence, the aim of the study is to investigate the potential antiangiogenic property of ACRH in human umbilical vein endothelial cells (HUVECs) and zebrafish embryo model. ACRH was separated from the crude ethanolic extract of the plant's root in prior to experimental studies. MTT assay revealed that ACRH exerted a concentration-dependent antiproliferative effect on HUVEC with the IC50 of 2.49 ± 0.04 μg/mL. At higher concentration (10 μg/mL), apoptosis was induced without affecting the cell cycle distribution. Angiogenic properties including migration, invasion and differentiation of HUVECs, evaluated via wound healing, trans-well invasion and tube formation assay respectively, were significantly suppressed by ACRH in a concentration-dependent manner. Noteworthily, significant antiangiogenic effects were observed even at the lowest concentration used (0.1 μg/mL). Expression of proMMP-2, vascular endothelial growth factor (VEGF)-C, VEGF-D, Angiopoietin-2, fibroblast growth factor (FGF)-1, FGF-2, Follistatin, and hepatocyte growth factor (HGF) were significantly reduced in various degrees by ACRH. The ISV formation in zebrafish embryo was significantly suppressed by ACRH at the concentration of 5 μg/mL. These findings revealed the potential of ACRH as antiangiogenic agent by suppressing multiple proangiogenic proteins. Thus, it can be further verified via the transcription of these proteins from their respective DNA, in elucidating their exact pathways.
    Matched MeSH terms: Human Umbilical Vein Endothelial Cells/pathology
  10. Camalxaman SN, Zeenathul NA, Quah YW, Loh HS, Zuridah H, Hani H, et al.
    In Vitro Cell Dev Biol Anim, 2013 Mar;49(3):238-44.
    PMID: 23435855 DOI: 10.1007/s11626-012-9553-5
    Endothelial cells have been implicated as key cells in promoting the pathogenesis and spread of cytomegalovirus (CMV) infection. This study describes the isolation and culture of rat brain endothelial cells (RBEC) and further evaluates the infectious potential of a Malaysian rat CMV (RCMV ALL-03) in these cultured cells. Brain tissues were mechanically fragmented, exposed to enzymatic digestion, purified by gradient density centrifugation, and cultured in vitro. Morphological characteristics and expression of von Willebrand factor (factor VIII-related antigen) verified the cells were of endothelial origin. RBEC were found to be permissive to the virus by cytopathic effects with detectable plaques formed within 7 d of infection. This was confirmed by electron microscopy examination which proved the existence of the viral particles in the infected cells. The susceptibility of the virus to these target cells under the experimental conditions described in this report provides a platform for developing a cell-culture-based experimental model for studies of RCMV pathogenesis and allows stimulation of further studies on host cell responses imposed by congenital viral infections.
    Matched MeSH terms: Endothelial Cells/pathology
  11. Safi SZ, Shah H, Qvist R, Bindal P, Mansor M, Yan GOS, et al.
    Cell Physiol Biochem, 2018;51(3):1429-1436.
    PMID: 30485834 DOI: 10.1159/000495591
    BACKGROUND/AIMS: NF-κB induces transcription of a number of genes, associated with inflammation and apoptosis. In this study, we have investigated the effect of β-adrenergic receptor stimulation on NF-κB and IκBα in HUVECs.

    METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in high and low glucose concentrations. All HUVECs were treated with different concentrations of isoproterenol and propranolol for different time periods. The analytical procedures consisted of Western Blot, ELISA, DCFH-DA and TUNEL assays.

    RESULTS: Isoproterenol (agonist of a beta-adrenergic receptor) significantly reduced phosphorylation at Ser-536 of NF-κB; and Ser-32 and Ser-36 of IκBα in hyperglycemic HUVECs. Isoproterenol also significantly reduced apoptosis and ROS generation. No effect of IκBα was observed on Tyr-42 phosphorylation. The effect of isoproterenol was reversed by the antagonist propranolol. We also checked if NF-κB inhibitor MG132 causes any change at the level of apoptosis. However, we observed an almost similar effect.

    CONCLUSION: Given data demonstrates that beta-adrenergic receptors stimulation has a protective effect on HUVECs that might be occuring via NF-κβ and IκBα pathway.

    Matched MeSH terms: Endothelial Cells/pathology
  12. Choy KW, Lau YS, Murugan D, Vanhoutte PM, Mustafa MR
    J. Pharmacol. Exp. Ther., 2018 03;364(3):420-432.
    PMID: 29259041 DOI: 10.1124/jpet.117.245217
    Inflammatory injury of the endothelium leads to apoptosis and endothelial dysfunction. The current study explored the effect and mechanisms of paeonol in inflammation-induced apoptosis and endothelial dysfunction induced by lipopolysaccharides (LPSs). The effects of paeonol on LPS-induced inflammatory injury were assessed by Western blotting, flow cytometry and reactive oxygen species (ROS) measurement in human umbilical vein endothelial cells (HUVECs) and C57BL/6J mice. Vascular reactivity of isolated mouse aortae was examined using wire myographs. The exposure of HUVECs to LPS increased the protein presence of Toll-like receptor 4 (TLR4), bone morphogenic protein 4 (BMP4), BMP receptor type 1A, nicotinamide adenine dinucleotide phosphate oxidase subunit 2, mitogen-activated protein kinase (MAPK), inducible nitric oxide synthase (iNOS), and cleaved caspase 3, as well as decreased it in phosphorylated endothelial nitric oxide synthase; these effects were prevented by treatment with paeonol. Similarly, cotreatment with paeonol reversed BMP4-induced apoptosis in HUVECs. Relaxation in response to the endothelium-dependent vasodilator acetylcholine were impaired in mouse aortae after exposure to LPSs; this endothelial dysfunction was reversed by cotreatment with paeonol, noggin (a BMP4 inhibitor), TAK242 (TLR4 antagonist), apocynin (an ROS scavenger), MAPK inhibitors, and AG (an iNOS inhibitor). BMP4 small interfering RNAs (siRNAs) abolished LPS-induced upregulation of BMP4 and cleaved caspase 3 protein, but not in cells treated with TLR4 siRNA and vice versa. The silencing of TLR4 and BMP4 abolished the inhibitory effects of paeonol on LPS-induced activation of cleaved caspase 3. The present results demonstrate that paeonol reduces LPS-induced endothelial dysfunction and apoptosis by inhibiting TLR4 and BMP4 signaling independently.
    Matched MeSH terms: Human Umbilical Vein Endothelial Cells/pathology
  13. Gangoda SVS, Avadhanam B, Jufri NF, Sohn EH, Butlin M, Gupta V, et al.
    Sci Rep, 2018 01 26;8(1):1689.
    PMID: 29374229 DOI: 10.1038/s41598-018-20117-6
    Amyloid β (Aβ) deposition is a hallmark of Alzheimer's disease (AD). Vascular modifications, including altered brain endothelial cell function and structural viability of the blood-brain barrier due to vascular pulsatility, are implicated in AD pathology. Pulsatility of phenomena in the cerebral vasculature are often not considered in in vitro models of the blood-brain barrier. We demonstrate, for the first time, that pulsatile stretch of brain vascular endothelial cells modulates amyloid precursor protein (APP) expression and the APP processing enzyme, β-secretase 1, eventuating increased-Aβ generation and secretion. Concurrent modulation of intercellular adhesion molecule 1 and endothelial nitric oxide synthase (eNOS) signaling (expression and phosphorylation of eNOS) in response to pulsatile stretch indicates parallel activation of endothelial inflammatory pathways. These findings mechanistically support vascular pulsatility contributing towards cerebral Aβ levels.
    Matched MeSH terms: Endothelial Cells/pathology*
  14. Clayton BA, Middleton D, Bergfeld J, Haining J, Arkinstall R, Wang L, et al.
    Emerg Infect Dis, 2012 Dec;18(12):1983-93.
    PMID: 23171621 DOI: 10.3201/eid1812.120875
    Human infections with Nipah virus in Malaysia and Bangladesh are associated with markedly different patterns of transmission and pathogenicity. To compare the 2 strains, we conducted an in vivo study in which 2 groups of ferrets were oronasally exposed to either the Malaysia or Bangladesh strain of Nipah virus. Viral shedding and tissue tropism were compared between the 2 groups. Over the course of infection, significantly higher levels of viral RNA were recovered from oral secretions of ferrets infected with the Bangladesh strain. Higher levels of oral shedding of the Bangladesh strain of Nipah virus might be a key factor in onward transmission in outbreaks among humans.
    Matched MeSH terms: Endothelial Cells/pathology
  15. Siar CH, Nakano K, Han PP, Nagatsuka H, Ng KH, Kawakami T
    J Oral Pathol Med, 2010 Aug 1;39(7):552-8.
    PMID: 20337864 DOI: 10.1111/j.1600-0714.2009.00871.x
    In mammals, the Notch gene family encodes four receptors (Notch1-4), and all of them are important for cell fate decisions. Notch signaling pathway plays an essential role in tooth development. The ameloblastoma, a benign odontogenic epithelial neoplasm, histologically recapitulates the enamel organ at bell stage. Notch has been detected in the plexiform and follicular ameloblastoma. Its activity in the desmoplastic ameloblastoma is unknown.
    Matched MeSH terms: Endothelial Cells/pathology
  16. Wong PF, Jamal J, Tong KL, Khor ES, Yeap CE, Jong HL, et al.
    Microvasc Res, 2017 11;114:26-33.
    PMID: 28595801 DOI: 10.1016/j.mvr.2017.06.002
    miRNAs are important regulators of cellular senescence yet the extent of their involvement remains to be investigated. We sought to identify miRNAs that are involved in cytokine-induced premature senescence (CIPS) in endothelial cells. CIPS was established in young human pulmonary microvascular endothelial cells (HMVEC-Ls) following treatment with a sublethal dose (20ng/ml) of tumor necrosis factor alpha (TNF-α) for 15days. In parallel, HMVEC-Ls were grown and routinely passaged until the onset of replicative senescence (RS). Differential expression analysis following miRNA microarray profiling revealed an overlapped of eight deregulated miRNAs in both the miRNA profiles of RS and TNF-α-induced premature senescence cells. Amongst the deregulated miRNAs were members of the miR 17-92 cluster which are known regulators of angiogenesis. The role of hsa-miR-20b in TNF-α-induced premature senescence, a paralog member of the miR 17-92 cluster, was further investigated. Biotin-labeled hsa-miR-20b captured the enriched transcripts of retinoblastoma-like 1 (RBL1), indicating that RBL1 is a target of hsa-miR-20b. Knockdown of hsa-miR-20b attenuated premature senescence in the TNF-α-treated HMVEC-Ls as evidenced by increased cell proliferation, increased RBL1 mRNA expression level but decreased protein expression of p16INK4a, a cellular senescence marker. These findings provide an early insight into the role of hsa-miR-20b in endothelial senescence.
    Matched MeSH terms: Endothelial Cells/pathology
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