Micro–RNA-126 Reduces the Blood Thrombogenicity in Diabetes Mellitus via Targeting of Tissue Factor

Witkowski, Marco; Weithäuser, Alice; Tabaraie, Termeh; Steffens, Daniel; Kränkel, Nicolle; Witkowski, Mario; Stratmann, Bernd; Tschöepe, Diethelm; Landmesser, Ulf; Rauch-Kroehnert, Ursula

doi:10.1161/atvbaha.115.306094

Cited by 74 publications

(62 citation statements)

References 42 publications

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“…To test whether stroke regulates miR-126 target gene and protein expression, selected specific miR-126 target genes and proteins (MCP-1 and VCAM-1 [31, 32]) were measured. Figure 3b, c shows that stroke increased heart tissue MCP-1 and VCAM-1 gene and protein expression compared to non-stroke control.…”

Section: Resultsmentioning

confidence: 99%

“…MCP1, VCAM-1, and Spred-1 are targets of miR-126 [38]; therefore, it is likely that stroke-induced decrease of miR-126 subsequently increased miR-126’s target gene expression. Reduced miR-126 expression may induce vascular inflammation by increasing the levels of VCAM-1, fibrinogen, and leukocyte counts [32]. MiR-126 binds directly to the 3′-untranslated region of MCP-1 mRNA and controls MCP-1 production in a human monocyte/macrophage cell line [31].…”

Section: Discussionmentioning

confidence: 99%

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MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke

Chen

Cui

Yang

et al. 2017

Transl. Stroke Res.

126

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Cardiovascular diseases are approximately three times higher in patients with neurological deficits than in patients without neurological deficits. MicroRNA-126 (MiR-126) facilitates vascular remodeling and decreases fibrosis and is emerging as an important factor in the pathogenesis of cardiovascular diseases and cerebral stroke. In this study, we tested the hypothesis that decreased miR-126 after ischemic stroke may play an important role in regulating cardiac function. Wild-type (WT), specific conditional-knockout endothelial cell miR-126 (miR-126EC−/−), and miR-126 knockout control (miR-126fl/fl) mice were subjected to distal middle cerebral artery occlusion (dMCAo) (n = 10/group). Cardiac hemodynamics and function were measured using transthoracic Doppler echocardiography. Mice were sacrificed at 28 days after dMCAo. WT mice subjected to stroke exhibited significantly decreased cardiac ejection fraction and increased myocyte hypertrophy, fibrosis as well as increased heart inflammation, infiltrating macrophages, and oxidative stress compared to non-stroke animals. Stroke significantly decreased serum and heart miR-126 expression and increased miR-126 target genes, vascular cell adhesion protein-1, and monocyte chemotactic protein-1 gene, and protein expression in the heart compared to non-stroke mice. MiR-126EC−/− mice exhibited significantly decreased cardiac function and increased cardiomyocyte hypertrophy, fibrosis, and inflammatory factor expression after stroke compared to miR-126fl/fl stroke mice. Exosomes derived from endothelial cells of miR-126EC−/− (miR-126EC−/−EC-Exo) mice exhibited significantly decreased miR-126 expression than exosomes derived from miR-126fl/fl (miR-126fl/fl-EC-Exo) mice. Treatment of cardiomyocytes subjected to oxygen glucose deprivation with miR-126fl/fl-EC-Exo exhibited significantly decreased hypertrophy than with miR-126EC−/−EC-Exo treatment. Ischemic stroke directly induces cardiac dysfunction. Decreasing miR-126 expression may contribute to cardiac dysfunction after stroke in mice.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke

Chen

Cui

Yang

et al. 2017

Transl. Stroke Res.

126

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show abstract

“…18 Indeed, endothelium-derived TF functionally participates in thrombosis. [19][20][21][22][23][24] In this regard, Witkowski et al 25 identified that circulating miR-126, which was primarily produced by ECs, 26 attenuated thrombosis via decreasing the expression of both mRNA and protein of TF. Their study showed that levels of plasma miR-126 were negatively correlated with concentrations and activities of plasma TF in diabetic patients.…”

Section: Tissue Factormentioning

confidence: 99%

Thrombotic Regulation From the Endothelial Cell Perspectives

Wang

Hao

Leeper

et al. 2018

ATVB

121

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“…Previous reports showed that miR-126 and -223 can post-transcriptionally downregulate TF expression in monocytes [113] and endothelial cells [114], respectively. These miRs can be upregulated in EOC cells [112].…”

Section: Potential Tf-fviia-driven Inflammatory Responses Within Hmentioning

confidence: 99%

Potential Coagulation Factor-Driven Pro-Inflammatory Responses in Ovarian Cancer Tissues Associated with Insufficient O2 and Plasma Supply

Koizume¹,

Miyagi²

2017

IJMS

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Tissue factor (TF) is a cell surface receptor for coagulation factor VII (fVII). The TF-activated fVII (fVIIa) complex is an essential initiator of the extrinsic blood coagulation process. Interactions between cancer cells and immune cells via coagulation factors and adhesion molecules can promote progression of cancer, including epithelial ovarian cancer (EOC). This process is not necessarily advantageous, as tumor tissues generally undergo hypoxia due to aberrant vasculature, followed by reduced access to plasma components such as coagulation factors. However, hypoxia can activate TF expression. Expression of fVII, intercellular adhesion molecule-1 (ICAM-1), and multiple pro-inflammatory cytokines can be synergistically induced in EOC cells in response to hypoxia along with serum deprivation. Thus, pro-inflammatory responses associated with the TF-fVIIa–ICAM-1 interaction are expected within hypoxic tissues. Tumor tissue consists of multiple components such as stromal cells, interstitial fluid, albumin, and other micro-factors such as proton and metal ions. These factors, together with metabolism reprogramming in response to hypoxia and followed by functional modification of TF, may contribute to coagulation factor-driven inflammatory responses in EOC tissues. The aim of this review was to describe potential coagulation factor-driven inflammatory responses in hypoxic EOC tissues. Arguments were extended to clinical issues targeting this characteristic tumor environment.

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Micro–RNA-126 Reduces the Blood Thrombogenicity in Diabetes Mellitus via Targeting of Tissue Factor

Cited by 74 publications

References 42 publications

MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke

MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke

Thrombotic Regulation From the Endothelial Cell Perspectives

Potential Coagulation Factor-Driven Pro-Inflammatory Responses in Ovarian Cancer Tissues Associated with Insufficient O2 and Plasma Supply

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