Endothelial to mesenchymal transition: at the axis of cardiovascular health and disease

Cardiovascular Research, Journal Year: 2024, Volume and Issue: 120(3), P. 223 - 236

Published: Feb. 1, 2024

Abstract Endothelial cells (ECs) line the luminal surface of blood vessels and play a major role in vascular (patho)-physiology by acting as barrier, sensing circulating factors intrinsic/extrinsic signals. ECs have capacity to undergo endothelial-to-mesenchymal transition (EndMT), complex differentiation process with key roles both during embryonic development adulthood. EndMT can contribute EC activation dysfunctional alterations associated maladaptive tissue responses human disease. During EndMT, progressively changes leading expression mesenchymal markers while repressing lineage-specific traits. This phenotypic functional switch is considered largely exist continuum, being characterized gradation transitioning stages. In this report, we discuss plasticity potential reversibility hypothesis that different EndMT-derived cell populations may disease progression or resolution. addition, review advancements field, current technical challenges, well therapeutic options opportunities context cardiovascular biology.

Language: Английский

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Extracellular vesicle microRNA transfer in cardiovascular disease

Cardiovascular Pathology, Journal Year: 2015, Volume and Issue: 24(4), P. 199 - 206

Published: May 2, 2015

Language: Английский

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Stromal Expression of miR-143/145 Promotes Neoangiogenesis in Lung Cancer Development

Cancer Discovery, Journal Year: 2016, Volume and Issue: 6(2), P. 188 - 201

Published: Jan. 11, 2016

The two unrelated miRNAs miR-143 and miR-145, coexpressed from the miR-143/145 cluster, have been proposed to act as tumor suppressors in human cancer, therapeutic benefits of delivering miR-145 tumors reported. In contrast, we found that tumor-specific deletion an autochthonous mouse model lung adenocarcinoma did not affect development. This was consistent with lack endogenous expression normal transformed epithelium. Surprisingly, microenvironment dramatically promoted growth by stimulating proliferation endothelial cells. Loss vivo led derepression target CAMK1D, inhibitory kinase, which when overexpressed prevents mitotic entry As a consequence, miR-143/145-deficient animals exhibited diminished neoangiogenesis, increased apoptosis, their expansion limited tumor's ability co-opt alveolar vasculature. These findings demonstrate stromal promotes tumorigenesis caution against use these agents cancer therapeutics.This study shows expressed stimulates neoangiogenesis supports lung, demonstrating surprising role for putative suppressor miRNA cluster promoting tumorigenesis. We propose inhibition avenue modulate neoangiogenesis.

Language: Английский

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Endothelial and Smooth Muscle Cell Interactions in the Pathobiology of Pulmonary Hypertension

American Journal of Respiratory Cell and Molecular Biology, Journal Year: 2016, Volume and Issue: 54(4), P. 451 - 460

Published: Jan. 8, 2016

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Language: Английский

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miR-128-3p Is a Novel Regulator of Vascular Smooth Muscle Cell Phenotypic Switch and Vascular Diseases

Circulation Research, Journal Year: 2020, Volume and Issue: 126(12)

Published: March 27, 2020

MicroRNAs (miRNAs, miRs) are small noncoding RNAs that modulate gene expression by negatively regulating translation of target genes. Although the role several miRNAs in vascular smooth muscle cells (VSMCs) has been extensively characterized, function miRNA-128-3p (miR-128) is still unknown.To determine if miR-128 modulates VSMC phenotype and to define underlying mechanisms.We screened for whose modulated an altered DNA methylation status VSMCs, among hits, we selected miR-128. We found was expressed various tissues, primary murine cells, pathological human specimens. Through gain- loss-of-function approaches, determined affects proliferation, migration, differentiation, contractility. The alterations those properties were dependent upon epigenetic regulation key differentiation genes; notably, Kruppel-like factor 4 be a direct able pivotal myosin heavy chain 11 (Myh11). Finally, vivo lentiviral delivery prevented intimal hyperplasia mouse model carotid restenosis without modifying vital cardiovascular parameters.miR-128 critical modulator VSMCs regulated modifications stress. Its modulation context disease could exploited therapeutic purposes.

Language: Английский

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The multifactorial nature of microRNAs in vascular remodelling

Cardiovascular Research, Journal Year: 2016, Volume and Issue: 110(1), P. 6 - 22

Published: Feb. 23, 2016

Vascular remodelling is a multifactorial process that involves both adaptive and maladaptive changes of the vessel wall through, among others, cell proliferation migration, but also apoptosis necrosis various types in wall. can be beneficial, e.g. during neovascularization after ischaemia, as well pathological, atherosclerosis aneurysm formation. In recent years, it has become clear microRNAs are able to target many genes involved vascular processes either promote or inhibit structural Since different regulated by similar mechanisms factors, positive negative affected same microRNAs. A large number been linked aspects indeed, several these regulate multiple processes, including angiogenesis arteriogenesis atherosclerosis, restenosis Here, we discuss role microRNA clusters were reported play forms clearly cardiovascular disease (CVD). The reviewed miR-126, miR-155 gene 17-92, 23/24/27, 143/145 14q32. Understanding contribution entire spectrum important, especially may have great potential therapeutic targets for treatment CVDs.

Language: Английский

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MicroRNAs for Restenosis and Thrombosis After Vascular Injury

Circulation Research, Journal Year: 2016, Volume and Issue: 118(7), P. 1170 - 1184

Published: March 31, 2016

Percutaneous revascularization revolutionized the therapy of patients with coronary artery disease. Despite continuous technical advances that substantially improved patients’ outcome after percutaneous revascularization, some issues are still open. In particular, restenosis represents a challenge, even though it was dramatically reduced advent drug-eluting stents. At same time, stent thrombosis emerged as major concern because incomplete or delayed re-endothelialization vascular injury. The discovery microRNAs revealed previously unknown layer regulation for several biological processes, increasing our knowledge on mechanisms underlying and thrombosis, revealing novel promising targets more efficient selective therapies. present review summarizes recent experimental clinical evidence role arterial injury, focusing practical aspects their potential therapeutic application inhibition smooth muscle cell proliferation, enhancement endothelial regeneration, platelet activation interventions. Application circulating biomarkers is also discussed.

Language: Английский

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MicroRNAs and Endothelial (Dys) Function

Journal of Cellular Physiology, Journal Year: 2015, Volume and Issue: 231(8), P. 1638 - 1644

Published: Dec. 2, 2015

Accumulating evidence indicates that microRNAs (miRs)—non-coding RNAs can regulate gene expression via translational repression and/or post-transcriptional degradation—are becoming one of the most fascinating areas physiology, given their fundamental roles in countless pathophysiological processes. The relative different miRs vascular biology as direct or indirect regulators genes implied remodeling designate potential biomarkers promising drug targets. mechanistic importance modulating endothelial cell (EC) function physiology and disease is addressed here. Drawbacks currently available therapeutic options are also discussed, pointing at challenges clinical opportunities provided by miR-based treatments. J. Cell. Physiol. 231: 1638–1644, 2016. © 2015 Wiley Periodicals, Inc.

Language: Английский

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TGF-β signaling controls FSHR signaling-reduced ovarian granulosa cell apoptosis through the SMAD4/miR-143 axis

Cell Death and Disease, Journal Year: 2016, Volume and Issue: 7(11), P. e2476 - e2476

Published: Nov. 24, 2016

Abstract Follicle-stimulating hormone receptor (FSHR) and its intracellular signaling control mammalian follicular development female infertility. Our previous study showed that FSHR is downregulated during atresia of porcine ovaries. However, role regulation in remain unclear. Here, we knockdown induced granulosa cell (pGC) apoptosis atresia, attenuated the levels molecules such as PKA, AKT p-AKT. was identified a target miR-143, microRNA upregulated atresia. miR-143 enhanced pGC by targeting FSHR, reduced molecules. SMAD4, final molecule transforming growth factor (TGF)- β signaling, bound to promoter significant downregulation vitro vivo . Activated TGF- rescued miR-143-reduced molecules, miR-143-induced apoptosis. Overall, our findings offer evidence explain how influences for specific microRNA, miR-143.

Language: Английский

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MicroRNA and ROS Crosstalk in Cardiac and Pulmonary Diseases

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(12), P. 4370 - 4370

Published: June 19, 2020

Reactive oxygen species (ROS) affect many cellular functions and the proper redox balance between ROS antioxidants contributes substantially to physiological welfare of cell. During pathological conditions, an altered equilibrium leads increased production that in turn may cause oxidative damage. MicroRNAs (miRNAs) regulate gene expression at post-transcriptional level contributing all major processes, including stress cell death. Several miRNAs are expressed response mediate stress. Conversely, lead upregulation control mechanisms buffer damage induced by ROS. This review focuses on complex crosstalk diseases cardiac (i.e., hypertrophy, heart failure, myocardial infarction, ischemia/reperfusion injury, diabetic cardiomyopathy) pulmonary idiopathic fibrosis, acute lung injury/acute respiratory distress syndrome, asthma, chronic obstructive disease, cancer) compartments. Of note, miR-34a, miR-144, miR-421, miR-129, miR-181c, miR-16, miR-31, miR-155, miR-21, miR-1/206 were found play a role during both pathologies. comprehensively summarizes current knowledge field.

Language: Английский

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