Hypoxia-Induced miR-210 Modulates Tissue Response to Acute Peripheral Ischemia

Zaccagnini, Germana; Maimone, Biagina; Stefano, Valeria Di; Fasanaro, Pasquale; Greco, Simona; Perfetti, Alessandra; Capogrossi, Maurizio C.; Gaetano, Carlo; Martelli, Fabio

doi:10.1089/ars.2013.5206

Cited by 47 publications

(78 citation statements)

References 49 publications

(86 reference statements)

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“…Indeed, we found that miR-210 is induced in a mouse model of hindlimb ischemia (158). Accordingly, Li et al propose miR-210 as serum biomarker for atherosclerosis obliterans (78).…”

Section: Hypoxamir Peripheral Artery Disease and Wound Healingmentioning

confidence: 64%

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HypoxamiR Regulation and Function in Ischemic Cardiovascular Diseases

Greco

Gaetano

Martelli

2014

Antioxidants & Redox Signaling

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Significance: MicroRNAs (miRNAs) are deregulated and play a causal role in numerous cardiovascular diseases, including myocardial infarction, coronary artery disease, hypertension, heart failure, stroke, peripheral artery disease, kidney ischemia-reperfusion. Recent Advances: One crucial component of ischemic cardiovascular diseases is represented by hypoxia. Indeed, hypoxia is a powerful stimulus regulating the expression of a specific subset of miRNAs, named hypoxia-induced miRNAs (hypoxamiR). These miRNAs are fundamental regulators of the cell responses to decreased oxygen tension. Certain hypoxamiRs seem to have a particularly pervasive role, such as miR-210 that is virtually induced in all ischemic diseases tested so far. However, its specific function may change according to the physiopathological context. Critical Issues: The discovery of HypoxamiR dates back 6 years. Thus, despite a rapid growth in knowledge and attention, a deeper insight of the molecular mechanisms underpinning hypoxamiR regulation and function is needed. Future Directions: An extended understanding of the function of hypoxamiR in gene regulatory networks associated with cardiovascular diseases will allow the identification of novel molecular mechanisms of disease and indicate the development of innovative therapeutic approaches.

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“…Indeed, we found that miR-210 is induced in a mouse model of hindlimb ischemia (158). Accordingly, Li et al propose miR-210 as serum biomarker for atherosclerosis obliterans (78).…”

Section: Hypoxamir Peripheral Artery Disease and Wound Healingmentioning

confidence: 64%

“…However, miR-210-HIF1A positive feedback may not be present in all tissues and/or physiopathological conditions. Indeed, we found that miR-210 blockade did not affect HIF1A-pathway activation in a mouse model of acute hindlimb ischemia (158).…”

Section: Hypoxia-inducible Factor 1: An Mirna-mediated Modulatormentioning

confidence: 77%

HypoxamiR Regulation and Function in Ischemic Cardiovascular Diseases

Greco

Gaetano

Martelli

2014

Antioxidants & Redox Signaling

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“…Ischemic brain injury, known as ischemic stroke, is caused by occlusion of a blood vessel, and the remarkable decrease in regional cerebral blood flow leads to hypoxia, glucose loss and brain damage [29]. Recent experiments demonstrated that ischemia-induced miRs act as negative regulators of genes, taking part in the treatment for acute and chronic ischemia [30, 31]. In this study, we investigated the effect of miR-381 targeting LRRC4 by the SDF-1/CXCR4 signaling pathway on the repair of nerve injury in rats with acute cerebral ischemia after CLB.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-381 Favors Repair of Nerve Injury Through Regulation of the SDF-1/CXCR4 Signaling Pathway via LRRC4 in Acute Cerebral Ischemia after Cerebral Lymphatic Blockage

Piao¹,

Wu²,

Yang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Acute cerebral ischemia is a manifestation of cerebral vascular insufficiency and has a high mortality. However, the therapy for acute cerebral ischemia is still limited. This study aimed to investigate the effect of microRNA-381 (miR-381) on the repair of nerve injury in rats with acute cerebral ischemia after cerebral lymphatic blockage (CLB) by targeting leucine-rich repeat C4 protein (LRRC4) through the Stromal cell-derived factor-1/CXC chemokine receptor-4 signaling pathway. Methods: Rat models of CLB and middle cerebral artery occlusion (MCAO) were established, and 56 Wistar rats were divided into sham, MCAO, CLB + MCAO, CLB + MCAO + miR-381 inhibitor, CLB + MCAO + miR-381 mimic, CLB + MCAO + AMD3100 and CLB + MCAO + miR-381 mimic + AMD3100 groups. Modified neurological severity score (mNSS was used to determine nerve injury, TTC staining to measure infarction volume, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry to evaluate cell apoptosis, immunofluorescence to measure BrdU-positive cell number, enzyme-linked immunosorbent assay (ELISA) to determine contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), nerve growth factor (NGF) and neurite outgrowth inhibitor -A (Nogo-A), Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting to evaluate expression of miR-381, LRRC4, SDF-1, CXCR4, pERK, Slit2 and vascular endothelial growth factor (VEGF). Results: LRRC4 was a target gene of miR-381. Compared with the results in the CLB + MCAO group, mNSS, infarction volume, apoptosis rate and TNF-α, IL-1β, IL-6 and Nogo-A contents as well as LRRC4 expression in the CLB + MCAO + miR-381 inhibitor and CLB + MCAO + AMD3100 groups were increased (those in the CLB + MCAO + AMD3100 group > those in the CLB + MCAO + miR-381 mimic + AMD3100 group), while BrdU-positive cell number, contents of NGF and IL-10, and expression of SDF-1, CXCR4, pERK, Slit2 and VEGF in brain tissues were decreased (those in the CLB + MCAO + AMD3100 group < those in the CLB + MCAO + miR-381 mimic + AMD3100 group). The results in the CLB + MCAO + mimic group were opposite of those in the CLB + MCAO + miR-381 inhibitor and CLB + MCAO + AMD3100 groups. Conclusion: Taken together, we concluded that up-regulation of miR-381 promoted nerve injury repair in acute cerebral ischemia rats after CLB by negatively regulating LRRC4 through activating the SDF-1/CXCR4 signaling pathway.

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“…The most notable hypoxia-miR, miR-210, is induced in ECs in a HIF-1α dependent manner [100]. Notably, miR-210 is upregulated also in cardiomyocytes undergoing hypoxia [101] and in whole ischemic muscles [102]. Induction of miR-210 in ECs is instrumental in downregulating genes that impair tubulogenesis and VEGF-induced chemotaxis, like EphrinA3 (EFNA3) [100] and apoptosis [101].…”

Section: Ischemic Injury and Micrornasmentioning

confidence: 99%

“…Delivery of miR-210 LNA in a model of hind-limb ischemia increases cell apoptosis and necrosis, further decreases capillary density and impairs limb perfusion. Gene expression analysis of ischemic gastrocnemius shows that the most affected pathways following by miR-210 inhibition were redox balance in cells and mitochondria function [102]. …”

Section: Ischemic Injury and Micrornasmentioning

confidence: 99%

MicroRNAs as regulators of endothelial cell functions in cardiometabolic diseases

Araldi

Suárez

2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Endothelial cells (ECs) provide nutrients and oxygen essential for tissue homeostasis. Metabolic imbalances and other environmental stimuli, like cytokines or low shear stress, trigger endothelial inflammation, increase permeability, compromise vascular tone, promote cell proliferation and ultimately cause cell death. These factors contribute to EC dysfunction, which is crucial in the development of cardiometabolic diseases. microRNAs (miRNAs) are small non-coding RNAs that have important functions in the regulation of ECs. In the present review, we discuss the role of miRNAs in various aspects of EC pathology in cardiometabolic diseases like atherosclerosis, type 2 diabetes, obesity, and the metabolic syndrome, and in complication of those pathologies, like ischemia. We also discuss the potential therapeutic applications of miRNAs in promoting angiogenesis and neovascularization in tissues where the endothelium is damaged in different cardiometabolic diseases.

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Hypoxia-Induced miR-210 Modulates Tissue Response to Acute Peripheral Ischemia

Abstract: The physiopathological significance of miR-210 is context dependent. In the ischemic skeletal muscle it seems to be cytoprotective, regulating oxidative metabolism and oxidative stress.

Cited by 47 publications

References 49 publications

HypoxamiR Regulation and Function in Ischemic Cardiovascular Diseases

HypoxamiR Regulation and Function in Ischemic Cardiovascular Diseases

MicroRNA-381 Favors Repair of Nerve Injury Through Regulation of the SDF-1/CXCR4 Signaling Pathway via LRRC4 in Acute Cerebral Ischemia after Cerebral Lymphatic Blockage

MicroRNAs as regulators of endothelial cell functions in cardiometabolic diseases

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