MicroRNA-30 mediates anti-inflammatory effects of shear stress and KLF2 via repression of angiopoietin 2

Demolli, Shemsi; Doebele, Carmen; Doddaballapur, Anuradha; Lang, Victoria; Fißlthaler, Beate; Chavakis, Emmanouil; Vinciguerra, Manlio; Sciacca, Sergio; Henschler, Reinhard; Hecker, Markus; Savant, Soniya; Augustin, Hellmut G.; Kaluza, David; Dimmeler, Stefanie; Boon, Reinier A.

doi:10.1016/j.yjmcc.2015.10.009

Cited by 52 publications

(33 citation statements)

References 48 publications

(51 reference statements)

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“…Moreover, miRNA profiling of human endometrium reveals cyclic changes in miR30b expression through the different physiological phases [43], and sex differences of miR30b levels were also observed in brains of female schizophrenic patients compared to males [44], suggesting the effect of physiological concentrations of estrogen on miR-30b regulation. In endothelial cells, miR-30 has also been implicated in angiogenesis processes [45], antiinflammatory effects by decreasing angiopoietin 2-induced VCAM1 expression [46] and apoptosis inhibition of human coronary artery endothelial cells [47]. In this regard, it is noteworthy that E2 has also pro-angiogenic, anti-inflammatory and anti-apoptotic properties in response to vascular injury [4].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

Vidal‐Gómez

Pérez‐Cremades

Mompeón

et al. 2018

Cell Physiol Biochem

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Background/Aims: Estrogen signalling plays an important role in vascular biology as it modulates vasoactive and metabolic pathways in endothelial cells. Growing evidence has also established microRNA (miRNA) as key regulators of endothelial function. Nonetheless, the role of estrogen regulation on miRNA profile in endothelial cells is poorly understood. In this study, we aimed to determine how estrogen modulates miRNA profile in human endothelial cells and to explore the role of the different estrogen receptors (ERα, ERβ and GPER) in the regulation of miRNA expression by estrogen. Methods: We used miRNA microarrays to determine global miRNA expression in human umbilical vein endothelial cells (HUVEC) exposed to a physiological concentration of estradiol (E2; 1 nmol/L) for 24 hours. miRNAgene interactions were computationally predicted using Ingenuity Pathway Analysis and changes in miRNA levels were validated by qRT-PCR. Role of ER in the E2-induced miRNA was additionally confirmed by using specific ER agonists and antagonists. Results: miRNA array revealed that expression of 114 miRNA were significantly modified after E2 exposition. Further biological pathway analysis revealed cell death and survival, lipid metabolism, reproductive system function, as the top functions regulated by E2. We validated changes in the most significantly increased (miR-30b-5p, miR-487a-5p, miR-4710, miR-501-3p) and decreased (miR-378h and miR-1244) miRNA and the role of ER in these E2-induced miRNA was determined. Results showed that both classical, ERα and ERβ, and membrane-bound ER, GPER, differentially regulated specific miRNA. In silico analysis of validated miRNA promoters identified specific ER binding sites. Conclusion: Our findings identify differentially expressed miRNA pathways linked to E2 in human endothelial cells through ER, and provide new insights by which estrogen can modulate endothelial function.

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Section: Discussionmentioning

confidence: 99%

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

Vidal‐Gómez

Pérez‐Cremades

Mompeón

et al. 2018

Cell Physiol Biochem

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“…Finally, laminar flow shear stress or KLF2 overexpression in ECs induce members of the miR-30-5p family that, in turn, decrease anti-inflammatory markers such as VCAM-1 and ICAM-1 by targeting angiopoietin-2. 91 However, a role for miR-30-5p family members in regulating endothelial inflammation and atherosclerosis in mice will require future investigation.…”

Section: Mechano-sensitive Ec Mirnas That Regulate Atherosclerosismentioning

confidence: 99%

MicroRNA Regulation of Atherosclerosis

Feinberg

Moore

2016

Circulation Research

531

407

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

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“…In addition to Tie1, laminar shear stimulates a polarized subcellular distribution of VE-PTP [144], and down-regulates Ang2 expression via KLF2 transcription-factor mediated miRNA regulation [145,146]. In vivo Ang2 is expressed in the atherosclerosis-prone region of the lesser curvature of the aortic arch, which experiences disturbed flow pattern [146].…”

Section: Ang–tie System In Vascular Diseasesmentioning

confidence: 99%

Angiopoietin–Tie signalling in the cardiovascular and lymphatic systems

Eklund¹,

Kangas²,

2016

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Endothelial cells that form the inner layer of blood and lymphatic vessels are important regulators of vascular functions and centrally involved in the pathogenesis of vascular diseases. In addition to the vascular endothelial growth factor (VEGF) receptor pathway, the angiopoietin (Ang)–Tie system is a second endothelial cell specific ligand–receptor signalling system necessary for embryonic cardiovascular and lymphatic development. The Ang–Tie system also regulates postnatal angiogenesis, vessel remodelling, vascular permeability and inflammation to maintain vascular homoeostasis in adult physiology. This system is implicated in numerous diseases where the vasculature has an important contribution, such as cancer, sepsis, diabetes, atherosclerosis and ocular diseases. Furthermore, mutations in the TIE2 signalling pathway cause defects in vascular morphogenesis, resulting in venous malformations and primary congenital glaucoma. Here, we review recent advances in the understanding of the Ang–Tie signalling system, including cross-talk with the vascular endothelial protein tyrosine phosphatase (VE-PTP) and the integrin cell adhesion receptors, focusing on the Ang–Tie system in vascular development and pathogenesis of vascular diseases.

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MicroRNA-30 mediates anti-inflammatory effects of shear stress and KLF2 via repression of angiopoietin 2

Cited by 52 publications

References 48 publications

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

MicroRNA Regulation of Atherosclerosis

Angiopoietin–Tie signalling in the cardiovascular and lymphatic systems

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