MicroRNA Regulation of Atherosclerosis

Circulation Research, Journal Year: 2016, Volume and Issue: 118(4), P. 703 - 720

Published: Feb. 18, 2016

Atherosclerosis and its attendant clinical complications, such as myocardial infarction, stroke, peripheral artery disease, are the leading cause of morbidity mortality in Western societies. In response to biochemical biomechanical stimuli, atherosclerotic lesion formation occurs from participation a range cell types, inflammatory mediators, shear stress. Over past decade, microRNAs (miRNAs) have emerged evolutionarily conserved, noncoding small RNAs that serve important regulators fine-tuners pathophysiological cellular effects molecular signaling pathways involved atherosclerosis. Accumulating studies reveal importance miRNAs regulating key lipid homeostasis alter balance plaque progression regression. this review, we highlight current paradigms miRNA-mediated atherosclerosis We provide an update on potential use diagnostically for detecting increasing severity coronary disease events. Finally, perspective therapeutic opportunities challenges miRNA delivery field.

Language: Английский

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Pathophysiology of Atherosclerosis

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(6), P. 3346 - 3346

Published: March 20, 2022

Atherosclerosis is the main risk factor for cardiovascular disease (CVD), which leading cause of mortality worldwide. initiated by endothelium activation and, followed a cascade events (accumulation lipids, fibrous elements, and calcification), triggers vessel narrowing inflammatory pathways. The resultant atheroma plaque, along with these processes, results in complications. This review focuses on different stages atherosclerosis development, ranging from endothelial dysfunction to plaque rupture. In addition, post-transcriptional regulation modulation microRNAs lncRNAs, role microbiota, importance sex as crucial are covered here order provide global view disease.

Language: Английский

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Brain–Heart Interaction

Circulation Research, Journal Year: 2017, Volume and Issue: 121(4), P. 451 - 468

Published: Aug. 3, 2017

Neurocardiology is an emerging specialty that addresses the interaction between brain and heart, is, effects of cardiac injury on heart. This review article focuses dysfunction in setting stroke such as ischemic stroke, hemorrhage, subarachnoid hemorrhage. The majority post-stroke deaths are attributed to neurological damage, cardiovascular complications second leading cause mortality. Accumulating clinical experimental evidence suggests a causal relationship damage heart dysfunction. Thus, it important determine whether triggered by unrelated complication, or underlying stroke. Stroke-induced may lead fatality potentially lifelong problems (such failure), mild recoverable neurogenic stress cardiomyopathy Takotsubo cardiomyopathy. role location lateralization lesions after brain-heart interaction; biomarkers manifestations complications; mechanisms hypothalamic-pituitary-adrenal axis; catecholamine surge; sympathetic parasympathetic regulation; microvesicles; microRNAs; gut microbiome, immunoresponse, systemic inflammation, discussed.

Language: Английский

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Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review

Cardiovascular Research, Journal Year: 2016, Volume and Issue: 111(4), P. 322 - 337

Published: June 29, 2016

The aim of the present study is to identify microRNAs (miRs) with high potential be used as biomarkers in plasma and/or serum clinically diagnose, or provide accurate prognosis for survival in, patients atherosclerosis, coronary artery disease, and acute syndrome (ACS). A systematic search published original research yielded a total 72 studies. After review risk bias studies, according Cochrane Collaboration QUADUAS Group standards, 19 studies were selected. Overall 52 different miRs reported. In particular, miR-133a/b (5 studies), miR-208a/b (6 miR-499 (7 studies) well studied found significant diagnostic prognostic markers across cardiovascular disease progression stages. miR-1 miR-145b are ACS; higher sensitivity all myocardial infarction (AMI), miR-145 STEMI worse outcome AMI. But when ACS populations, had varying degrees stenosis, which was identified an important confounder that limited ability quantitatively pool results. regulate endothelial function angiogenesis (miR-1, miR-133), vascular smooth muscle cell differentiation (miR-133, miR-145), communication between stabilize plaques (miR-145), apoptosis miR-133, miR-499), cardiac myocyte miR-145, miR-208, repress hypertrophy (miR-133). Their role these processes may explained by regulation shared RNA targets such cyclin-dependent kinase inhibitor 1A (or p21), ETS proto-oncogene 1, fascin actin-bundling protein hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, insulin-like growth factor 1 receptor LIM SH3 purine nucleoside phosphorylase, transgelin 2. These mechanistic data further support clinical relevance miRs. miR-1, miR-133a/b, miR-208a/b, miR-499(a) show some diagnosis disease. However, biased selection most unexplained contrasting results major limitations current miR research. Inconsistencies need addressed order definitively useful Therefore, this paper presents aspects improve future research, including unbiased miRs, standardization/normalization reference adjustment patient comorbidities medication, robust protocols data-sharing plans could prevent selective publication reporting outcomes.

Language: Английский

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RNA-Seq Identifies Circulating miR-125a-5p, miR-125b-5p, and miR-143-3p as Potential Biomarkers for Acute Ischemic Stroke

Circulation Research, Journal Year: 2017, Volume and Issue: 121(8), P. 970 - 980

Published: July 20, 2017

Currently, there are no blood-based biomarkers with clinical utility for acute ischemic stroke (IS). MicroRNAs show promise as disease markers because of their cell type-specific expression patterns and stability in peripheral blood.To identify circulating microRNAs associated IS, determine temporal course up to 90 days post-stroke, explore an early diagnostic marker.We used RNA sequencing study changes a discovery sample 20 patients IS matched healthy control subjects. We further applied quantitative real-time polymerase chain reaction independent samples validation (40 40 controls), replication (200 100 subjects), 72 transient attacks. Sampling patient plasma was done immediately upon hospital arrival. identified, validated, replicated 3 differentially expressed microRNAs, which were upregulated compared both subjects (miR-125a-5p [1.8-fold; P=1.5×10-6], miR-125b-5p [2.5-fold; P=5.6×10-6], miR-143-3p [4.8-fold; P=7.8×10-9]) attack (miR-125a-5p: P=0.003; miR-125b-5p: miR-143-3p: P=0.005). Longitudinal analysis levels after revealed normalization starting at day 2 while miR-125a-5p remained elevated. Levels all depended on platelet numbers spike-in experiment but unaffected by chemical hypoxia Neuro2a cells experimental models. In random forest classification, miR-125a-5p, miR-125b-5p, differentiated between area under the curve 0.90 (sensitivity: 85.6%; specificity: 76.3%), superior multimodal cranial computed tomography obtained routine diagnostics 72.5%) previously reported (neuron-specific enolase: curve=0.69; interleukin 6: curve=0.82).A set (miR-125a-5p, miR-143-3p) associates might have marker.

Language: Английский

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Role of long non-coding RNA-RNCR3 in atherosclerosis-related vascular dysfunction

Cell Death and Disease, Journal Year: 2016, Volume and Issue: 7(6), P. e2248 - e2248

Published: June 2, 2016

Abstract Atherosclerosis is one of the most common vascular disorders. Endothelial cell (EC) dysfunction and smooth muscle (VSMC) proliferation contributes to development atherosclerosis. Long non-coding RNAs (lncRNAs) have been implicated in several biological processes human diseases. Here we show that lncRNA-RNCR3 expressed ECs VSMCs. RNCR3 expression significantly upregulated mouse aortic atherosclerotic lesions, cultured VSMCs upon ox-LDL treatment vitro . knockdown accelerates atherosclerosis, aggravates hypercholesterolemia inflammatory factor releases, decreases EC VSMC vivo also reduces migration, apoptosis vitro. acts as a ceRNA, forms feedback loop with Kruppel-like 2 miR-185-5p regulate function. This study reveals has an atheroprotective role its intervention promising strategy for treating atherosclerosis-related dysfunction.

Language: Английский

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RETRACTED ARTICLE: N6-methyladenosine induced miR-143-3p promotes the brain metastasis of lung cancer via regulation of VASH1

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Dec. 10, 2019

Abstract Background Brain metastasis (BM) is one of the principal causes mortality for lung cancer patients. While molecular events that govern BM remain frustrating cloudy. Methods The miRNA expression profiles are checked in paired human and primary tissues. effect miR-143-3p on cells its related mechanisms investigated. Results upregulated tissues as compared with It can increase invasion capability vitro blood brain barrier (BBB) model angiogenesis by targeting three binding sites 3’UTR vasohibin-1 (VASH1) to inhibit expression. Mechanistically, VASH1 ubiquitylation VEGFA trigger proteasome mediated degradation, further, it endow tubulin depolymerization through detyrosination cell motility. m 6 A methyltransferase Mettl3 splicing precursor facilitate biogenesis. Moreover, miR-143-3p/VASH1 axis acts adverse prognosis factors vivo progression overall survival (OS) rate cancer. Conclusions Our work implicates a causal role cancers suggests their critical roles pathogenesis.

Language: Английский

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Smooth Muscle Enriched Long Noncoding RNA ( SMILR ) Regulates Cell Proliferation

Circulation, Journal Year: 2016, Volume and Issue: 133(21), P. 2050 - 2065

Published: April 7, 2016

Background— Phenotypic switching of vascular smooth muscle cells from a contractile to synthetic state is implicated in diverse pathologies, including atherogenesis, plaque stabilization, and neointimal hyperplasia. However, very little known about the role long noncoding RNA (lncRNA) during this process. Here, we investigated for lncRNAs cell biology pathology. Methods Results— Using sequencing, identified >300 whose expression was altered human saphenous vein following stimulation with interleukin-1α platelet-derived growth factor. We focused on novel lncRNA (Ensembl: RP11-94A24.1), which termed muscle–induced enhances replication ( SMILR ). Following stimulation, increased both nucleus cytoplasm, detected conditioned media. Furthermore, knockdown markedly reduced proliferation. Mechanistically, noted that genes proximal also by interleukin-1α/platelet-derived factor treatment, HAS2 knockdown. In samples, observed unstable atherosclerotic plaques levels plasma patients high C-reactive protein. Conclusions— These results identify as driver proliferation suggest modulation may be therapeutic strategy reduce pathologies.

Language: Английский

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Circ_Lrp6, a Circular RNA Enriched in Vascular Smooth Muscle Cells, Acts as a Sponge Regulating miRNA-145 Function

Circulation Research, Journal Year: 2019, Volume and Issue: 124(4), P. 498 - 510

Published: Jan. 17, 2019

microRNAs (miRNAs) modulate gene expression by repressing translation of targeted genes. Previous work has established a role for miRNAs in regulating vascular smooth muscle cell (VSMC) activity. Whether circular RNAs are involved the modulation miRNA activity VSMCs is unknown.We aimed to identify interacting with enriched and modulating cells' activity.RNA sequencing bioinformatics identified several VSMCs; however, only one, possessing multiple putative binding sites miR-145, was highly conserved between mouse man. This RNA gemmed from alternative splicing Lrp6 (lipoprotein receptor 6), expressed vessels implicated pathologies thus named circ_Lrp6. Its as miR-145 sponge confirmed determining reciprocal interaction through immunoprecipitation, stimulated emission depletion microscopy, competitive luciferase assays; functional inhibition assessed measuring target genes ITGβ8 (integrin-β8), FASCIN (fascin actin-bundling protein 1), KLF4 (Kruppel-like factor 4), Yes1 (YES proto-oncogene Lox (lysyl oxidase). The preferentially localized P-bodies, mRNA degradation. Using loss- gain-of-function approaches, we found that circ_Lrp6 hindered miR-145-mediated regulation VSMC migration, proliferation, differentiation. Differential murine human diseases suggests ratio bound versus unbound could play pathogenesis. Viral delivery shRNA prevented intimal hyperplasia carotids.circ_Lrp6 an intracellular modulator natural counterbalancing functions VSMCs.

Language: Английский

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Flow-induced reprogramming of endothelial cells in atherosclerosis

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 20(11), P. 738 - 753

Published: May 24, 2023

Atherosclerotic diseases such as myocardial infarction, ischaemic stroke and peripheral artery disease continue to be leading causes of death worldwide despite the success treatments with cholesterol-lowering drugs drug-eluting stents, raising need identify additional therapeutic targets. Interestingly, atherosclerosis preferentially develops in curved branching arterial regions, where endothelial cells are exposed disturbed blood flow characteristic low-magnitude oscillatory shear stress. By contrast, straight regions stable flow, which is associated high-magnitude, unidirectional stress, relatively well protected from through shear-dependent, atheroprotective cell responses. Flow potently regulates structural, functional, transcriptomic, epigenomic metabolic changes mechanosensors mechanosignal transduction pathways. A study using single-cell RNA sequencing chromatin accessibility analysis a mouse model flow-induced demonstrated that reprogrammes situ healthy phenotypes diseased ones characterized by inflammation, endothelial-to-mesenchymal transition, endothelial-to-immune cell-like transition changes. In this Review, we discuss emerging concept disturbed-flow-induced reprogramming (FIRE) potential pro-atherogenic mechanism. Defining mechanisms reprogrammed promote crucial area research could lead identification novel targets combat high prevalence atherosclerotic disease. Jo colleagues involved dysfunction atherosclerosis, including mechanism, highlight targeting flow-sensitive genes, proteins

Language: Английский

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