Vascular Endothelial Cells and Innate Immunity

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2020, Volume and Issue: 40(6)

Published: May 27, 2020

In addition to the roles of endothelial cells (ECs) in physiological processes, ECs actively participate both innate and adaptive immune responses. We previously reported that, comparison macrophages, a prototypic cell type, have many functions that macrophages carry out, including cytokine secretion, phagocytic function, antigen presentation, pathogen-associated molecular patterns-, danger-associated patterns-sensing, proinflammatory, immune-enhancing, anti-inflammatory, immunosuppression, migration, heterogeneity, plasticity. this highlight, we introduce recent advances published ATVB other journals: (1) several significant characters classify as novel not only infections allograft transplantation but also metabolic diseases; (2) new receptor systems conditional pattern receptors, nonpattern homeostasis associated patterns receptors contribute ECs; (3) immunometabolism memory determine (4) great induction checkpoint during inflammations suggests tolerogenic (5) association inhibitors with cardiovascular adverse events cardio-oncology indicates potential contributions cells.

Language: Английский

---

A macrophage-specific lncRNA regulates apoptosis and atherosclerosis by tethering HuR in the nucleus

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Dec. 1, 2020

Long non-coding RNAs (lncRNAs) are emerging regulators of pathophysiological processes including atherosclerosis. Using RNA-seq profiling the intima lesions, here we identify a macrophage-specific lncRNA MAARS (Macrophage-Associated Atherosclerosis Sequence). Aortic expression increases by 270-fold with atherosclerotic progression and decreases regression 60%. knockdown reduces lesion formation 52% in LDLR

Language: Английский

---

Vascular remodelling in cardiovascular diseases: hypertension, oxidation, and inflammation

Clinical Science, Journal Year: 2024, Volume and Issue: 138(13), P. 817 - 850

Published: June 26, 2024

Abstract Optimal vascular structure and function are essential for maintaining the physiological functions of cardiovascular system. Vascular remodelling involves changes in vessel structure, including its size, shape, cellular molecular composition. These result from multiple risk factors may be compensatory adaptations to sustain blood function. They occur diverse pathologies, hypertension heart failure atherosclerosis. Dynamic endothelium, fibroblasts, smooth muscle cells, pericytes or other wall cells underlie remodelling. In addition, immune macrophages lymphocytes, infiltrate vessels initiate inflammatory signalling. contribute a dynamic interplay between cell proliferation, apoptosis, migration, inflammation, extracellular matrix reorganisation, all critical mechanisms Molecular pathways underlying these processes include growth (e.g., endothelial factor platelet-derived factor), cytokines interleukin-1β tumour necrosis factor-α), reactive oxygen species, signalling pathways, such as Rho/ROCK, MAPK, TGF-β/Smad, related nitric oxide superoxide biology. MicroRNAs long noncoding RNAs crucial epigenetic regulators gene expression We evaluate potential therapeutic targeting clinical translational perspective. summary, remodelling, coordinated modification function, is disease pathology.

Language: Английский

---

Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics

Pharmacology & Therapeutics, Journal Year: 2018, Volume and Issue: 196, P. 15 - 43

Published: Nov. 13, 2018

Language: Английский

---

Role of flow-sensitive microRNAs and long noncoding RNAs in vascular dysfunction and atherosclerosis

Vascular Pharmacology, Journal Year: 2018, Volume and Issue: 114, P. 76 - 92

Published: Oct. 7, 2018

Language: Английский

---

Endothelial dysfunction in diabetes and hypertension: Role of microRNAs and long non-coding RNAs

Life Sciences, Journal Year: 2018, Volume and Issue: 213, P. 258 - 268

Published: Oct. 17, 2018

Language: Английский

---

Atherosclerosis and flow: roles of epigenetic modulation in vascular endothelium

Journal of Biomedical Science, Journal Year: 2019, Volume and Issue: 26(1)

Published: Aug. 7, 2019

Endothelial cell (EC) dysfunctions, including turnover enrichment, gap junction disruption, inflammation, and oxidation, play vital roles in the initiation of vascular disorders atherosclerosis. Hemodynamic forces, i.e., atherprotective pulsatile (PS) pro-atherogenic oscillatory shear stress (OS), can activate mechanotransduction to modulate EC function dysfunction. This review summarizes current studies aiming elucidate epigenetic factors, histone deacetylases (HDACs), non-coding RNAs, DNA methyltransferases (DNMTs), hemodynamics-regulated OS enhances expression nuclear accumulation class I II HDACs induce dysfunction, proliferation, whereas PS induces phosphorylation-dependent export inhibit overexpression III HDAC Sirt1 enhance nitric oxide (NO) production prevent In addition, hemodynamic forces acetylation transcription retinoic acid receptor α krüppel-like factor-2, transcriptionally regulate microRNAs (miRs). OS-modulated miRs, which stimulate proliferative, pro-inflammatory, oxidative signaling, promote PS-regulated anti-proliferative, anti-inflammatory, anti-oxidative also modulates long RNAs influence function. turnover, aligmant, migration. On other hand, DNMT-1 -3a NO repression.Overall, factors modulating hemodynamic-directed dysfunction disorders, Understanding detailed mechanisms through hemodynamics-directed help us pathogenic atherosclerosis develop potential therapeutic strategies for treatment.

Language: Английский

---

Long Non-coding RNA in CNS Injuries: A New Target for Therapeutic Intervention

Molecular Therapy — Nucleic Acids, Journal Year: 2019, Volume and Issue: 17, P. 754 - 766

Published: July 29, 2019

CNS injuries, such as traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral (ICH), and cerebral ischemic stroke, are important causes of death long-term disability worldwide. As an class pervasive genes involved in many pathophysiological processes, long non-coding RNAs (lncRNAs) have received attention the past decades. Multiple studies indicate that lncRNAs abundant a key role function well neurological disorders, especially injuries. Several investigations deciphered regulation exert pro-angiogenesis, anti-apoptosis, anti-inflammation effects via different molecules pathways, including microRNA (miRNA), nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB), phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase (PI3K/AKT), Notch, p53. Thus, show great promise molecular targets In this article, we provide updated review current state our knowledge about relationship between highlighting specific roles injuries one leading modern society, resulting high medical costs.1Wang Y. Tan H. Hui X. Biomaterial Scaffolds Regenerative Therapy Central Nervous System.BioMed Res. Int. 2018; 2018: 7848901PubMed Google Scholar usually include stroke.2Huang Young W. Chen L. Feng S. Zoubi Z.M.A. Sharma H.S. Saberi Moviglia G.A. He Muresanu D.F. et al.Clinical Cell Guidelines for Neurorestoration (IANR/CANR 2017).Cell Transplant. 27: 310-324Crossref PubMed Scopus (17) The pathological processes series events, inflammation, oxidative stress, apoptosis, autophagy, blood-brain barrier (BBB) disruption, eventually result neuronal cell brain.3Boguszewska-Czubara A. Budzynska B. Skalicka-Wozniak K. Kurzepa J. Perspectives new aspects metalloproteinases' inhibitors therapy disorders: from chemistry to medicine.Curr. Med. Chem. (Published online May 13, 2018)https://doi.org/10.2174/0929867325666180514111500Crossref (9) Despite efforts on searching effective methods, patients suffering with severe always end up poor prognosis. Therefore, strategies treatment urgently needed reduce heavy disease economic burden. Long known RNA transcripts greater than 200 nucleotides.4Roberts T.C. Morris K.V. Weinberg M.S. mechanism transcriptional by RNAs.Epigenetics. 2014; 9: 13-20Crossref (113) Although were primarily considered simply by-products, accumulated evidence suggests participate various physiological immunity, differentiation, proliferation, survival, modulating stability retention their target genes.5Lee K.T. Nam J.W. Post-transcriptional translational mRNA-like microRNAs early developmental stages zebrafish embryos.BMB Rep. 2017; 50: 226-231Crossref (0) regulate gene expression at epigenetic, transcriptional, post-transcriptional, chromatin remodeling levels,6Bali K.K. Kuner R. Noncoding RNAs: understanding treating pain.Trends Mol. 20: 437-448Abstract Full Text PDF Scholar, 7Batista P.J. Chang H.Y. noncoding cellular address codes development disease.Cell. 2013; 152: 1298-1307Abstract (1940) they can activate or inhibit directly binding recruiting transcription factors (Figure 1).8Li Z. Li C. Shen Tse G. Chan M.T.V. Wu W.K.K. nucleus pulposus intervertebral disc degeneration.Cell Prolif. 51: e12483Crossref (1) Studies shown dysregulation was implicated human diseases.9Dharap Nakka V.P. Vemuganti Effect focal ischemia RNAs.Stroke. 2012; 43: 2800-2802Crossref (150) 10Wu P. Zuo Deng Liu Ji Roles development, functional diversification neurodegenerative diseases.Brain Bull. 97: 69-80Crossref (279) 11Schmitt A.M. Cancer Pathways.Cancer Cell. 2016; 29: 452-463Abstract (2120) 12Grammatikakis I. Panda A.C. Abdelmohsen Gorospe M. RNAs(lncRNAs) hallmarks aging.Aging (Albany N.Y.). 6: 992-1009Crossref 13Booton Lindsay M.A. Emerging MicroRNAs respiratory disease.Chest. 146: 193-204Abstract (117) Moreover, profiles associated neuroanatomical regions, types, suggesting potential nervous system.14Ramos A.D. Diaz Nellore Delgado R.N. Park K.Y. Gonzales-Roybal Oldham M.C. Song J.S. Lim D.A. Integration genome-wide approaches identifies adult neural stem progeny vivo.Cell Stem 12: 616-628Abstract (193) 15Mercer T.R. Dinger M.E. Sunkin S.M. Mehler M.F. Mattick Specific mouse brain.Proc. Natl. Acad. Sci. USA. 2008; 105: 716-721Crossref (927) 16Hong S.H. Kwon J.T. Kim Jeong Lee Cho Profiling testis-specific mice.BMC Genomics. 19: 539Crossref (6) altered contributed diverse disorders injuries.17Qureshi I.A. evolution, plasticity disease.Nat. Rev. Neurosci. 13: 528-541Crossref (437) 18Spadaro P.A. Bredy T.W. plasticity, cognitive function, neuropsychiatric disorders.Front. Genet. 3: 132Crossref (31) addition, gain- loss-of-function found played injury-induced secondary damage.19He D. Wang Lu Zhao Xu Hu Y.C. Zhou Q.R. lncRNA Functional Networks Oligodendrocytes Reveal Stage-Specific Myelination Control lncOL1/Suz12 Complex CNS.Neuron. 93: 362-378Abstract (79) regard, potentially is important. present study, overview functions mechanisms. During assessing lncRNAs, it revealed may act onco- tumor-suppressor numerous cancer types.20Shi Sun Yao frontier study diseases.Cancer Lett. 339: 159-166Crossref (976) This observation led into models. Recently, elucidated. Numbers aberrantly expressed identified using techniques microarray sequencing (RNA-seq).21Dykstra-Aiello Jickling G.C. Ander B.P. Shroff N. Zhan Hull Orantia Stamova B.S. Sharp F.R. Altered Expression Blood After Ischemic Stroke Proximity Putative Risk Loci.Stroke. 47: 2896-2903Crossref (98) 22Zhang Yuan Zhang Hamblin M.H. Zhu T. Meng F. Y.E. Yin K.J. transcriptomic microvascular endothelium after ischemia.Exp. Neurol. 277: 162-170Crossref (158) Specifically, metastasis lung adenocarcinoma transcript 1 (MALAT1), maternally 3 (MEG3), brain-derived neurotrophic antisense (BDNF-AS), enriched (NEAT1), growth arrest-specific 5 (GAS5), CAMK2D-associated (C2dat1) affect models (Table 1).Table 1The Functions Molecular Targets InjurieslncRNAsModelsAnimals and/or CellsExpressionBeneficial Regulation lncRNAsMolecular TargetsANRILMACOrats, HUVECsincreasedpromote angiogenesis, decrease infarction inflammationNF-κBBDNF-ASH/R injuryHCNs, astrocytesincreasedincrease MMP, ameliorate apoptosisPI3K/AKTC2dat1I/R injurymice, neuronsincreasedpromote inflammationNF-κBFosDTMCAOratsincreasedameliorate motor deficits, infarct volumeRESTGAS5HIBDrats, rat neuronsincreasedreduce size, improve recoverymiR-23aGm4419TBImouse astrocytesincreaseddecrease deficitsmiR-4661OGD/R injuryrat microglial cellsincreasedreduce neuroinflammationNF-κBH19OGD/R injurymiceincreasedattenuate deficits inflammation–I/R injuryrats, SH-SY5Y cellsincreaseddecrease autophagy–MALAT1OGD/R neuronsincreasedattenuate protect BBB functionmiR-30aBMECsincreasedpromote apoptosismiR-26b, PI3K/AKTMEG3hypoxic injuryPC12 cellsincreasedattenuate apoptosismiR-147MCAOmice, rats, HMECsincreasedameliorate lesion, promote angiogenesisNotch, miR-181bSAHrats, neuronsincreaseddecrease apoptosisPI3K/AKTOGD/R injuryHT22 cellsincreasedimprove attenuate apoptosismiR-181bN1LRI/R injuryratsincreasedenhance functionp53OGD/R injuryN2a cellsNEAT1TBIratsincreasedimprove death–NKILAICHrats, neuronsdecreasedinduce inflammationNF-κBRMSTOGD/R injurymouse function–MCAOmiceSNHG1OGD/R injuryBMECsincreasedpromote survival angiogenesismiR-199aTUG1MACOratsincreaseddecrease functionmiR-9OGD/R neuronslncRNAs, RNAs; ANRIL, INK4 locus; MCAO, middle artery occlusion; HUVECs, umbilical vein endothelial cells; NF-κB, BDNF-AS, RNA; H/R, hypoxia-reoxygenation; HCNs, cortical neurons; mitochondrial membrane potential; PI3K/AKT, B; C2dat1, CaMK2D-associated 1; I/R, ischemia-reperfusion; FosDT, Fos downstream transcript; GAS5, 5; HIBD, hypoxic/ischemic damage; miRNAs, microRNAs; OGD/R, oxygen-glucose deprivation/reoxygenation; TBI, injury; MALAT1, metastasis-associate BMECs, MEG3, 3; HMECs, SAH, hemorrhage; NEAT1, ICH, RMST, rhabdomyosarcoma 2-associated SNHG1, small nucleolar host TUG1, taurine-upregulated 1. Open table tab conserved, stable, (6.5 kb), initially be upregulated solid tumors metastasis, recurrence.23Chang Du Hou MALAT1 silencing suppresses prostate progression upregulating miR-1 downregulating KRAS.OncoTargets Ther. 11: 3461-3473Crossref (50) However, growing indicates has special regeneration injury. It abundantly vascular cells, skeletal muscle, cardiomyocytes participated inflammatory myogenesis, angiogenesis.24Qiao Peng LncRNA neuroprotective model spinal cord ischemia-reperfusion through miR-204 regulation.Curr. Neurovasc. 15: 211-219Crossref (7) been could (BMECs) caused deprivation-reoxygenation serving autophagy inducer.25Li Tang Malat1 potent inducer protecting against deprivation/reoxygenation-induced sponging miR-26b ULK2 expression.Neuroscience. 354: 1-10Crossref damage hyperglycemia-induced inflammation previously reported.26Puthanveetil Gautam Chakrabarti regulates hyperglycaemia induced process cells.J. 2015; 1418-1425Crossref (293) MEG3 ∼1.6 kb imprinted belonging DLK1-MEG3 locus located chromosome 14q32.3 DLK1 humans. There 12 generated alternative splicing, encodes approximately 1700 nucleotides.27Mondal Subhash Vaid Enroth Uday Reinius Mitra Mohammed James A.R. Hoberg E. al.MEG3 TGF-β pathway formation RNA-DNA triplex structures.Nat. Commun. 7743Crossref first tumor suppressor.28Ji suppressor choriocarcinoma upregulation microRNA-211.J Physiol. 2019; 23, 2019)https://doi.org/10.1002/jcp.28853Crossref (14) Subsequent results necessary neurons resist injuries.29Liu Q. K.S. Niu S.G. Luo Y.P. Z.F. Downregulation Non-Coding Meg3 Promotes Angiogenesis Brain Injury Activating Notch Signaling.Mol. Neurobiol. 54: 8179-8190Crossref (99) observed mediate activating p53 both vitro vivo.30Bao Szeto V. Yang B.B. S.Z. Z.P. stroke.Cell Death Dis. 281Crossref (163) downregulation enhance neurobehavioral outcomes.29Liu Furthermore, functioned competing endogenous miR-181b 12/15-LOX occlusion-induced nerve cells.31Liu Huang Gao Lv Mechanism Non-coding Neurons Apoptosis Caused Hypoxia: Mediated miR-181b-12/15-LOX Signaling Pathway.Front. 10: 201Crossref (63) BDNF member neurotrophin family factors. during embryonic contributes system synchronizing glial maturation participating axonal dendritic differentiation.32Marler Suetterlin Dopplapudi Rubikaite Adnan Maiorano N.A. Lowe A.S. Thompson I.D. Pathania Bordey al.BDNF promotes axon branching retinal ganglion miRNA-132 p250GAP.J. 34: 969-979Crossref (70) brain, acts hippocampus, cortex, basal forebrain—areas vital learning, memory, higher thinking, supporting growth, survival.33Song J.H. Yu Brain-Derived Neurotrophic Factor Alzheimer's Disease: Risk, Mechanisms, Therapy.Mol. 52: 1477-1493Crossref (66) thought beneficial disorders.34Sona Kumar Dogra B.A. Umrao Yadav P.N. Docosahexaenoic acid modulates GPR40 alleviates diabesity-associated learning memory mice.Neurobiol. 118: 94-107Crossref (29) BDNF-AS type transcribed polymerase II without open reading frame.35Modarresi Faghihi Lopez-Toledano Fatemi R.P. Magistri Brothers S.P. van der Brug M.P. Wahlestedt Inhibition natural vivo gene-specific upregulation.Nat. Biotechnol. 30: 453-459Crossref (480) Chromatin immunoprecipitation showed reduced localization EZH2 H3K27me3 promoter region inhibited BDNF, thereby affecting differentiation cells. increased protein levels differentiation.35Modarresi Besides, significantly infarction, whereas interfering (siRNA) suppressed hypoxia-reoxygenation (H/R)-induced neurotoxicity activation BDNF.36Zhong J.B. Zhong J.D. C.B. X.Y. Knockdown attenuates hypoxia/reoxygenation-induced apoptosis BDNF-TrkB-PI3K/Akt signaling pathway.Neuroreport. 28: 910-916Crossref recent declared knockdown novel method prevent (ESC)-derived neurons.37Zheng Lin Ye Guo ketamine-induced derived neurons.Biomed. Pharmacother. 82: 722-728Crossref (16) NEAT1 ∼3.2 lncRNA. localizes structures called paraspeckles essential maintenance paraspeckles.38Liu Mao Ton Regulatory reproductive disease.Am. Transl. 1-12PubMed Paraspeckles formed paraspeckle (PSP)1, PSP2, p54nrb start site. corpus luteum mammary gland modulate cytoplasmic proteins migrating cytoplasm.39Yu Zheng M.T. W.K. NEAT1: A cancer-related RNA.Cell 50Google proposed distributed subcellular regions where no observed,40Nakagawa Naganuma Shioi Hirose subpopulation-specific bodies not mice.J. Biol. 2011; 193: 31-39Crossref (225) other besides formation. also investigated. For example, downregulated response activity.41Barry Briggs J.A. Hwang D.W. Nayler Fortuna P.R. Jonkhout Dachet Maag J.L. Mestdagh Singh E.M. al.The responsive activity hyperexcitability states.Sci. 7: 40127Crossref (67) promoted septic mice positively regulating while si-NEAT1 transfection injury.42Liu W.Q. Y.J. Effects sepsis-induced NF-κB.Eur. Pharmacol. 23: 3933-3939PubMed play subjected lethal harm undergoing exerted regulatory effect apoptosis.43Hirose Virnicchi Tanigawa Kimura Yokoi Nakagawa Bénard Fox A.H. Pierron sequestration within subnuclear bodies.Mol. 25: 169-183Crossref (291) GAS5 hosts number (snoRNAs) its introns. So originally biological mediated introns.20Shi arrest serum starvation lack factors.44Simion Haemmig Feinberg M.W. LncRNAs biology disease.Vascul. 114: 145-156Crossref cause slower cycle increase apoptosis.45Shi Kong critical proliferation non-small-cell cancer.Mol. Carcinog. E1-E12Crossref (249) These suggeste plays normal apoptosis. unexpected discovered. previous highly hippocampus TBI quantitative real-time PCR analysis, might processes.46Wang C.F. C.C. Weng W.J. Lei G.Y. J.F. Jiang J.Y. Alteration Traumatic Rats.J. Neurotrauma. 2100-2108Crossref (39) Further confirmed pro-apoptotic miR-335 Rasa1 model.47Dai Yi Changqin NO. inhibits suppressing model.Biol. 400: 753-763Crossref (2) promising therapeutic (HIBD).48Zhao R.B. L.H. Shu J.P. Qiao L.X. Xia Z.K. protects hypoxia/ischemia-induced neonatal injury.Biochem. Biophys. 497: 285-291Crossref (28) C2dat1 sense overlaps introns 13–15 exon 14 CaMK2D genome.49Xu Xing Cen Nepomuceno Bhuiyan M.I. al.Long CaMKIIδ NF-κB following ischemia.Cell e2173Crossref (89) discovered array analysis occlusion (MCAO) 2016.49Xu mainly N2a inhibition suppression mRNA protein.50Jia Proliferation, Migration, Invasion Targeting miR-34a-5p Osteosarcoma Cells.Oncol. 26: 753-764Crossref indicated interact directly. murine ischemia/reperfusion (I/R) upon deprivation/reoxygenation (OGD/R). CAMK2D/CaMKIIδ OGD/R C2dat1-induced expression, further promoting pathway.49Xu Besides six well-studied there explored models, BC048612,51Kaur J.R. Karolina D.S. Sepramaniam Armugam Wong P.T. Jeyaseelan RNA, BC048612 microRNA, miR-203 coordinate regulator (NEGR1) adhesion protein.Biochim. Acta. 1863: 533-543Crossref (8) Uc.173,52Nan Dai ultraconserved Uc.173, molecul

Language: Английский

---

Long noncoding RNAs: a missing link in osteoporosis

Bone Research, Journal Year: 2019, Volume and Issue: 7(1)

Published: March 27, 2019

Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk, particularly the vertebrae hip. This condition associated morbidity mortality increase with population ageing. Long noncoding (lnc) RNAs are transcripts longer than 200 nucleotides not translated into proteins, but play important regulatory roles transcriptional post-transcriptional regulation. Their contribution to onset development increasingly recognized. Herein, we present an integrative revision on studies implicate lncRNAs osteoporosis support their potential use as therapeutic tools. Firstly, current evidence involvement cellular molecular mechanisms linked its major complication, fragility fractures, reviewed. We analyze osteogenesis, osteoclastogenesis, healing events from human animal model studies. Secondly, alterations at genetic transcriptomic level discussed risk factors new circulating biomarkers for diagnosis. Finally, conclude debating possibilities, persisting difficulties, future prospects using treatment osteoporosis.

Language: Английский

---

<p>The role of long non-coding RNA GAS5 in cancers</p>

Cancer Management and Research, Journal Year: 2019, Volume and Issue: Volume 11, P. 2729 - 2737

Published: April 1, 2019

Long non-coding RNAs (lncRNAs) have shown potential as a biomarker in the diagnosis and prognosis multiple cancers. LncRNAs are dysregulated various cancers, playing either oncogenic or tumor suppressive roles. Emerging evidences proved that growth arrest-specific 5 (GAS5) lncRNA can function suppressor several LncRNA GAS5 is downregulated many types of cancer, regulating cellular processes such cell proliferation, apoptosis invasion. The low level expression often elevates capacity proliferation predicts poorer some This review aims to summarize recent published literature on biogenesis, regulation mechanism different cancers explore its for cancer diagnosis, treatment.

Language: Английский

---