Vascular smooth muscle cells in intimal hyperplasia, an update

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 4, 2023

Arterial occlusive disease is the leading cause of death in Western countries. Core contemporary therapies for this include angioplasties, stents, endarterectomies and bypass surgery. However, these treatments suffer from high failure rates due to re-occlusive vascular wall adaptations restenosis. Restenosis following surgery largely intimal hyperplasia. Intimal hyperplasia develops response vessel injury, inflammation, smooth muscle cells dedifferentiation, migration, proliferation secretion extra-cellular matrix into vessel’s innermost layer or intima. In review, we describe current state knowledge on origin mechanisms underlying dysregulated hyperplasia, present new avenues research targeting VSMC phenotype proliferation.

Language: Английский

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Role of acetylation in doxorubicin-induced cardiotoxicity

Redox Biology, Journal Year: 2021, Volume and Issue: 46, P. 102089 - 102089

Published: July 31, 2021

As a potent chemotherapeutic agent, doxorubicin (DOX) is widely used for the treatment of variety cancers However, its clinical utility limited by dose-dependent cardiotoxicity, and pathogenesis has traditionally been attributed to formation reactive oxygen species (ROS). Accordingly, prevention DOX-induced cardiotoxicity an indispensable goal optimize therapeutic regimens reduce morbidity. Acetylation emerging important epigenetic modification regulated histone deacetylases (HDACs) acetyltransferases (HATs). Despite extensive studies molecular basis biological functions acetylation, application acetylation as target in initial stage, further are required clarify complex network improve management cardiotoxicity. In this review, we summarize pivotal HDACs HATs oxidative stress, underlying mechanisms, contributions noncoding RNAs (ncRNAs) exercise-mediated Furthermore, describe research progress related several SIRT activators HDAC inhibitors with potential value chemotherapy Collectively, comprehensive understanding specific roles recent developments doxorubicin-induced will provide improved outcomes cancer cardiovascular diseases.

Language: Английский

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Pathogenesis and Clinical Significance of In-Stent Restenosis in Patients with Diabetes

International Journal of Environmental Research and Public Health, Journal Year: 2021, Volume and Issue: 18(22), P. 11970 - 11970

Published: Nov. 15, 2021

Diabetes mellitus (DM) is a strong risk factor for the development of cardiovascular diseases such as coronary heart disease, cerebrovascular and peripheral arterial disease (PAD). In population people living with DM, PAD characterised by multi-level atherosclerotic lesions well greater involvement arteries below knee. DM also that significantly increases lower limb amputation. Percutaneous balloon angioplasty or without stent implantation an important method treatment diseases, but restenosis limiting its long-term effectiveness. The pathogenesis atherosclerosis in course differs slightly from general population. more attention drawn to factors inflammation, endothelial dysfunction, platelet blood rheological properties, hypercoagulability, additional stimulating vascular smooth muscle cell proliferation. restenosis. purpose this paper provide review literature present most information on current state knowledge mechanisms clinical significance in-stent patients especially association endovascular PAD. role processes neointimal hyperplasia neoatherosclerosis, allergy, resistance antimitotic drugs used coating stents balloons, genetic factors, technical mechanical are discussed. collected publication may be helpful planning further research field, which contribute formulation precise recommendations practice.

Language: Английский

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The cellular function and molecular mechanism of formaldehyde in cardiovascular disease and heart development

Journal of Cellular and Molecular Medicine, Journal Year: 2021, Volume and Issue: 25(12), P. 5358 - 5371

Published: May 10, 2021

As a common air pollutant, formaldehyde is widely present in nature, industrial production and consumer products. Endogenous mainly produced through the oxidative deamination of methylamine catalysed by semicarbazide-sensitive amine oxidase (SSAO) ubiquitous human body fluids, tissues cells. Vascular endothelial cells smooth muscle are rich this formaldehyde-producing enzyme easily damaged owing to consequent cytotoxicity. Consistent with this, increasing evidence suggests that cardiovascular system stages heart development also susceptible harmful effects formaldehyde. Exposure from different sources can induce disease such as arrhythmia, myocardial infarction (MI), failure (HF) atherosclerosis (AS). In particular, long-term exposure high concentrations pregnant women more likely affect embryonic cause malformations than low Specifically, ability mouse embryos effect clearance far lower rat embryos, readily allowing its accumulation. Formaldehyde may exert toxic on inducing stress cardiomyocyte apoptosis. This review focuses current progress understanding influence underlying mechanisms development.

Language: Английский

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NanoZnO-modified titanium implants for enhanced anti-bacterial activity, osteogenesis and corrosion resistance

Journal of Nanobiotechnology, Journal Year: 2021, Volume and Issue: 19(1)

Published: Oct. 30, 2021

Abstract Titanium (Ti) implants are widely used in dentistry and orthopedics owing to their excellent corrosion resistance, biocompatibility, mechanical properties, which have gained increasing attention from the viewpoints of fundamental research practical applications. Also, numerous studies been carried out fine-tune micro/nanostructures Ti and/or incorporate chemical elements improve overall implant performance. Zinc oxide nanoparticles (nano-ZnO) well-known for good antibacterial properties low cytotoxicity along with ability synergize a variety substances, received increasingly widespread as biomodification materials implants. In this review, we summarize recent progress on nano-ZnO modified Ti-implants. Their preparation methods Ti-implants introduced, followed by further presentation antibacterial, osteogenic, anti-corrosion these Finally, challenges future opportunities proposed. Graphical

Language: Английский

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Biodegradable Iron-Based Materials—What Was Done and What More Can Be Done?

Materials, Journal Year: 2021, Volume and Issue: 14(12), P. 3381 - 3381

Published: June 18, 2021

Iron, while attracting less attention than magnesium and zinc, is still one of the best candidates for biodegradable metal stents thanks its biocompatibility, great elastic moduli high strength. Due to low corrosion rate, thus slow biodegradation, iron have not been put into use. While these problems fully resolved, many studies published that propose different approaches issues. This brief overview report summarises latest developments in field iron-based presents some techniques can accelerate their biocorrosion rate. Basic data related metabolism mechanism process, as well a critical look at rate degradation systems obtained by several methods are included. All this illustrates title says, what was done within topic materials more be done.

Language: Английский

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Stimulus-Responsive Drug Delivery Nanoplatforms for Inflammatory Bowel Disease Therapy

Acta Biomaterialia, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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5′-tiRNA-Cys-GCA regulates VSMC proliferation and phenotypic transition by targeting STAT4 in aortic dissection

Molecular Therapy — Nucleic Acids, Journal Year: 2021, Volume and Issue: 26, P. 295 - 306

Published: July 29, 2021

Accumulating evidence shows that tRNA-derived fragments are a novel class of functional small non-coding RNA; however, their roles in aortic dissection (AD) still unknown. In this study, we found 5′-tiRNA-Cys-GCA was significantly downregulated human and mouse models dissection. The abnormal proliferation, migration, phenotypic transition vascular smooth muscle cells (VSMCs) played crucial role the initiation progression dissection, with as potential switching regulator, because its overexpression inhibited proliferation migration VSMCs increased expression contractile markers. addition, verified signal transducer activator transcription 4 (STAT4) direct downstream target 5′-tiRNA-Cys-GCA. We STAT4 upregulation oxidized low-density lipoprotein (ox-LDL)-treated VSMCs, which promoted cell transformation, reversed by Furthermore, treatment reduced incidence prevented malignant process angiotensin II- β-aminopropionitrile-induced AD mice. conclusion, our findings reveal is regulator pathological via signaling pathway, providing clinical for development future strategies IntroductionThe definition rupture intima due to various reasons, causing blood from orifice enter wall, forming arterial wall separation..1Sun Y. Xiao Sun H. Zhao Z. Zhu J. Zhang L. Dong Han T. Jing Q. Zhou miR-27a regulates remodeling targeting endothelial cells' apoptosis interaction dissection.Theranostics. 2019; 9: 7961-7975Crossref PubMed Scopus (21) Google Scholar,2Cheng M. Yang Xin Li Zong He X. Yu Non-coding RNAs dissection: From biomarkers therapeutic targets.J. Cell. Mol. Med. 2020; 24: 11622-11637Crossref (20) Scholar Eighty percent patients die rupture;3Thompson R.W. Detection management aneurysms.N. Engl. 2002; 346: 1484-1486Crossref (45) hence, once occurs, patient should be immediately hospitalized given surgical intervention. (VSMCs), an important constituent vessels, believed play onset AD.4Liu S. Jiang Tang N. Tian Ponnusamy Tariq M.A. Lian Understanding RNA (ncRNA) stent restenosis.Atherosclerosis. 2018; 272: 153-161Abstract Full Text PDF (36) have prominent feature called flexibility, enables them alternate between (differentiated) synthetic (dedifferentiated) phenotypes.5Li F.J. C.L. Luo X.J. Peng T.L. Involvement MiR-181b-5p/HMGB1 Pathway Ang II-induced Phenotypic Transformation Smooth Muscle Cells Hypertension.Aging Dis. 10: 231-248Crossref (24) Scholar, 6Wang C.Q. G.Y. Huang H.Y. Y.S. Ji Z.C. Shen Z.Y. MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Switch Migration Thoracic Aortic Dissection.Mol. Ther. Nucleic Acids. 16: 284-294Abstract (28) 7Davis-Dusenbery B.N. Wu C. Hata A. Micromanaging differentiation modulation.Arterioscler. Thromb. Vasc. Biol. 2011; 31: 2370-2377Crossref (180) 8Fu P. Wang Zou et al.Nicotine: Regulatory mechanisms atherosclerosis progression.Food Chem. Toxicol. 2021; 151: 112154Crossref (18) Contractile characterized high α-smooth actin (α-SMA) capabilities. contrast, contain low levels markers exhibit migration.9Owens G.K. Kumar M.S. Wamhoff B.R. Molecular regulation disease.Physiol. Rev. 2004; 84: 767-801Crossref (2536) accelerate occurrence alternations caused stimulants, such (ox-LDL) platelet-derived growth factor BB (PDGF-BB).10Inamoto Kwartler C.S. Lafont A.L. Liang Y.Y. Fadulu V.T. Duraisamy Willing Estrera Safi Hannibal M.C. al.TGFBR2 mutations alter phenotype predispose thoracic aneurysms dissections.Cardiovasc. Res. 2010; 88: 520-529Crossref (100) 11Jones J.A. Beck Barbour J.R. Zavadzkas Mukherjee R. Spinale F.G. Ikonomidis J.S. Alterations cellular constituents during aneurysm development: myofibroblast-mediated remodeling.Am. Pathol. 2009; 175: 1746-1756Abstract (54) 12Wang Liu Yuan Suppression miR-4463 promotes treated Ox-LDL.Cell Tissue 383: 1155-1165Crossref (7) Vascular involves subsequently damaging state balance.13McMurtry Bonnet Dyck Haromy Hashimoto K. Michelakis E.D. Dichloroacetate prevents reverses pulmonary hypertension inducing artery apoptosis.Circ. 95: 830-840Crossref (371) Scholar,14Yang Guo Meng Aung L.H.H. Targeting epigenome in-stent restenosis: therapy.Mol. 23: 1136-1160Abstract addition also link progression.15Liao W.L. Tan M.W. Xu Brahma-related gene 1 inhibits directly up-regulating Ras-related associated diabetes pathophysiologic processes dissection.J. Thorac. Cardiovasc. Surg. 2015; 150 (1292–301.e2)Abstract (16) Scholar,16Wang Fu W. D. Association phenotypes extracellular matrix disorders dissection.J Vasc 2012; 56: 1698-1709Abstract (72) Recent studies confirmed compared control group, samples more common.17Xiao Ma G. al.MicroRNA-22 Inhibits Apoptosis Cell p38MAPKα Remodeling 22: 1051-1062Abstract (13) Scholar,18Shi B. MST1 down-regulation decreasing apoptosis.Eur. Pharmacol. Sci. 2044-2051PubMed Therefore, elucidation involved conversion under conditions essential new diagnosis AD.The stress-induced (tiRNAs) kind newly discovered produced mature tRNAs.14Yang Scholar,19Li Sheng tRNA-Derived Small RNA: A Novel Non-Coding RNA.Genes (Basel). 246Crossref (148) 20Li J.X. Piwi-interacting (piRNAs) targets cardiovascular diseases.Angiogenesis. 19-34Crossref (26) 21Yang P.F. miRNAs diagnostic disease particular focus on WO2010091204.Expert Opin. Pat. 2017; 27: 1021-1029Crossref (32) Under specific conditions, tRNAs cleaved angiogenin (ANG), position anticodon loop will produce two kinds tiRNAs. These tiRNAs 5′-tiRNAs 3′-tiRNAs, length approximately 28–36 nts.16Wang Scholar,22Saikia Krokowski Guan B.J. Ivanov Parisien Hu G.F. Anderson Pan Hatzoglou Genome-wide identification quantitative analysis tRNA induced stress.J. 287: 42708-42725Abstract (147) 23Yamasaki Angiogenin cleaves translational repression.J. 185: 35-42Crossref (572) 24He Expression profiles transfer RNA-derived atherosclerosis.J. 25: 7052-7065Crossref (9) 25Zhang R.C. function molecular mechanism formaldehyde heart development.J. 5358-5371Crossref (15) 26Yang Zhan Shan Ding al.Blood TfR+ exosomes separated pH-responsive method deliver chemotherapeutics tumor therapy.Theranostics. 7680-7696Crossref (50) report tiRNAs, may biological functions, abnormally expressed or participate certain diseases, cancer, neurological, metabolic, viral infectious diseases.26Yang 27Shen Yan Transfer halves: biogenesis, functions diseases.J. (Berl.). 96: 1167-1176Crossref (104) 28Zhang Shi Cao Gao Ren Ning al.Identification characterization ancient enriched serum associating active infection.J. 2014; 6: 172-174Crossref 29Qi Selective arginine deprivation single injection non-uptake deiminase nanocapsules sustained inhibition.Nanoscale. 12: 24030-24043Crossref 30Qi Xue Stability Maintenance Protein Drugs Organic Coatings Based Nanogels.Pharmaceutics. 115Crossref (11) Notably, recent 5′-tiRNA regulating cancer cells31Mo Mao Wei F. fragment, 5′-tiRNAVal, suppresses Wnt/β-catenin pathway FZD3 breast cancer.Cancer Lett. 457: 60-73Crossref (66) biomarker ischemia-reperfusion damage death.32Elkordy Rashad Shehabeldeen Mishima E. Niizuma Abe Tominaga assessment vitro model rat neuronal PC12 cells.Brain 1714: 8-17Crossref However, relationship diseases whether altering unknown.Signal member STAT family.33Verhoeven Tilborghs Jacobs De Waele Quatannens Deben Prenen Pauwels Trinh X.B. Wouters al.The controversy family members cancer.Semin. Cancer 60: 41-56Crossref (113) protein located surfaces.34Lv Ye deficiency protects against neointima formation following injury mice.J. Cardiol. 74: After phosphorylation JAK proteins, proteins nucleus, combine transcripts, regulate genes related differentiation.35Guo Zarella Wagner W.D. atherosclerosis.Exp. 2006; 81: 15-22Crossref highly organs, including testis, spleen, heart, brain, thymus.36Yamamoto Kobayashi Arai Miura O. Hirosawa Miyasaka cDNA cloning, chromosome mapping gene: both STAT1 mapped 2q32.2-->q32.3.Cytogenet. Genet. 1997; 77: 207-210Crossref several can detected main apoptosis.34Lv Scholar,35Guo hypothesized cells.Our study explores AD. Our shed light identify regulatory pathways VSMCs. Future research focused present interventional AD.ResultsDifferential localization vivo vitroWe first level aorta. normal aorta, co-localized α-SMA, suggesting most likely (Figure 1A). Moreover, tissue lower than aorta (Figures 1A 1B). Consistent these data, mice 2.5× 1C). suggest serve protective To further investigate function, mimicked treating ox-LDL (100 μg/mL), plays vital VSMCs.37Xue Cho J.Y. Functional ginsenosides Panax ginseng Ginseng 45: 22-31Crossref (46) 38Tang Noncoding mellitus.Cardiovasc. 36: e12436Crossref 39Bai Chu X.M. NLRP3 inflammasome dysfunction.Cell Death 11: 776Crossref (116) 40He Long PEBP1P2 Suppresses Proliferative Switching Proliferation Atherosclerosis.Mol. 84-98Abstract (34) 41Wang noncoding XXYLT1-AS2 adhesion binding FUS HUVEC.Atherosclerosis. 298: 58-69Abstract 42Liu al.Insights into circRNA angiogenesis implications.Atherosclerosis. 14-26Abstract (55) 43Yu Jie Kim kinase inhibitor BX795 inflammatory response multiple kinases.Biochem. 174: 113797Crossref (29) Interestingly, after treatment, exhibited downward trend time-dependent manner 1D). Together, results indicate abundantly close association AD; were interested studying AD.Overexpression then synthesized transfected mimics 24 h transfection 2A), indicating successfully incorporated cells. counting kit-8 (CCK-8) experiment performed same showed 2B). 5-ethynyl-2′-deoxyuridine (EdU) assay inhibitory effect 2C). suppressed ability wound healing 2D) Transwell assays 2E). next determined observed 2F), specifically while calponin (CNN1) myosin heavy chain (SMHC) did not show significant changes.9Owens By rates change 2H), detecting apoptosis-related p53 caspase-3 (c-caspase-3; Figure 2G).44Du Qian Chen Zheng Pu Xia Aloin Preconditioning Attenuates Hepatic Ischemia/Reperfusion Injury TLR4/MyD88/NF-κB Signal Vivo Vitro.Oxid. Longev. 2019: 3765898Crossref (30) Scholar,45Su Lv X.W. Y.L. Cai R.P. Dai R.X. X.H. W.K. Kong B.H. Exosomal LINC00174 derived attenuates myocardial I/R p53-mediated autophagy apoptosis.Mol. 1304-1322Abstract summary, mainly regulated affect VSMCs.Figure 2Overexpression vitroShow full caption(A) used overexpress using real-time PCR. (B C) (B) cell-light EdU staining (C) measure at 0, 12, 24, 36 h. (D E) analyzed wound-healing (D) (E) assay. (F) Western blotting analyses conducted (G H) TUNEL (G) western blot (H) detect Data presented mean ± SD. Each repeated least three times. Scale bars, 200 μm. ∗p < 0.05; ∗∗p 0.01; ∗∗∗p 0.001; ∗∗∗∗p 0.0001; ns, significant.View Large Image ViewerDownload Hi-res image Download (PPT)Knockdown vitroThe knockdown 3A), consequently 3B 3C). Simultaneously, accelerated 3D 3E), 3F). any 3G 3H). validating 3Knockdown inhibitors down-express qPCR. CCK-8 down-expression ware (PPT)5′-tiRNA-Cys-GCA binds downregulates STAT4Investigation 5′-tiRNA-Cys-GCA-mediated KEGG ontology (GO) identified total 153 predicted 4A). revealed only 9 migration. targets, namely STAT4, PC nanoparticles (PCNP), cysteine rich secretory LCCL domain containing 2 (CRISPLD2), pulled down 4B). PCR (qPCR) remaining six (JAK3, KCNE3, HBEGF, TLR4, TREM1, TNFAIP8L2) undetermined Ct values, very levels. had highest enrichment, implying it probable Using miRanda TargetScan software, site 4C) structure score, free energy, Context+ values 145, −24.79, −0.303, respectively. Further displayed degree conservation humans, mice, rats 4C). Additional experiments mRNA 4D) 4E), correspondingly expression. Finally, dual luciferase reporter fluorescence intensities overexpressed wild-type plasmid reduced, there no mutant group. Taken together, bind activities.Figure 45′-tiRNA-Cys-GCA STAT4Show Predicted kyoto encyclopaedia genomes (KEGG) enrichment predictions, literature review pull-down selected. Pull-down Theoretically STAT4. qPCR NC STAT4-3′ UTR-WT mut co-transfected NC. Luciferase activity decreased (PPT)STAT4 ox-LDL-induced transformation 5′-tiRNA-Cys-GCAWe designed interfering (siRNA)-mediated validate 5′-tiRNA-Cys-GCA/STAT4 axis First, siRNA knocks

Language: Английский

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Multistage-Responsive Nanocomplexes Attenuate Ulcerative Colitis by Improving the Accumulation and Distribution of Oral Nucleic Acid Drugs in the Colon

ACS Applied Materials & Interfaces, Journal Year: 2022, Volume and Issue: 14(1), P. 2058 - 2070

Published: Jan. 3, 2022

Oral gene therapy has emerged as a potential optimal treatment for ulcerative colitis (UC). Nucleic acid drugs possessing versatility can not only inhibit inflammation but realize colon mucosal healing, fulfilling the clinical objective of UC therapy. However, effective accumulation and distribution oral nucleic in remain considerable challenge. Furthermore, current delivery systems pay more attention to colon, while which plays key role treatment, never catches researchers. Here, we used miR-320 model drug develop kind multistage-responsive nanocomplexes (MSNs) based on polymeric nanocapsules alginate. MSNs possess pH responsiveness stomach, enzyme colonic lumen, redox cytoplasm. In vivo imaging results showed that reach within 2 h effectively release lumen. The further deliver submucosal layer even muscular layer. Moreover, decreased activity myeloperoxidase proinflammatory cytokines exhibited anti-inflammatory by inhibiting phosphorylation IκBα AKT, reducing enhancing repair. Therefore, successfully alleviate improving promoting translational application UC.

Language: Английский

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Targeting non-coding RNAs in unstable atherosclerotic plaques: Mechanism, regulation, possibilities, and limitations

International Journal of Biological Sciences, Journal Year: 2021, Volume and Issue: 17(13), P. 3413 - 3427

Published: Jan. 1, 2021

Cardiovascular diseases (CVDs) caused by arteriosclerosis are the leading cause of death and disability worldwide. In late stages atherosclerosis, atherosclerotic plaque gradually expands in blood vessels, resulting vascular stenosis. When unstable ruptures falls off, it blocks vessel causing thrombosis, to strokes, myocardial infarctions, a series other serious that endanger people's lives. Therefore, regulating stability is main means used address high mortality associated with CVDs. The progression complex integration cell apoptosis, lipid metabolism disorders, inflammatory infiltration, smooth muscle migration, neovascular infiltration. More recently, emerging evidence has demonstrated non-coding RNAs (ncRNAs) play significant role pathophysiological process formation affecting biological functions vasculature its cells. purpose this paper comprehensively review regulatory mechanisms involved susceptibility rupture, discuss limitations current approaches treat instability, highlight potential clinical value ncRNAs as novel diagnostic biomarkers therapeutic strategies improve reduce risk major cardiovascular events.

Language: Английский

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