scholarly journals Neutrophil microvesicles drive atherosclerosis by deliveringmiR-155to atheroprone endothelium

2018 ◽  
Author(s):  
Ingrid Gomez ◽  
Ben Ward ◽  
Celine Souilhol ◽  
Chiara Recarti ◽  
Mark Ariaans ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Risk Factor ◽  
High Fat Diet ◽  
Vascular Inflammation ◽  
Atherosclerotic Plaques ◽  
High Fat ◽  
Complex Flow ◽  
Inflammatory Gene Expression ◽  
Disturbed Flow

AbstractNeutrophils have been implicated in the pathogenesis of atherosclerosis, a lipid-driven disease of arteries, but they are seldom found in atherosclerotic plaques. To resolve this longstanding paradox, we investigated whether neutrophil-derived microvesicles may influence arterial pathophysiology. Clinical and pre-clinical studies revealed that levels of circulating neutrophil microvesicles were enhanced by exposure to a high fat diet, a known risk factor for atherosclerosis. Neutrophil microvesicles accumulated at disease-prone regions of arteries that are exposed to complex flow patterns, and they promoted vascular inflammation and atherosclerosis in a murine model. Using cultured endothelial cells exposed to disturbed flow, it was demonstrated that neutrophil microvesicles promoted inflammatory gene expression by delivering a microRNA (miR-155) that enhanced NF-κB activation. Similary, neutrophil microvesicles increased miR-155 and enhanced NF-κB at disease-prone sites of disturbed flow in arteries of mice. We conclude that delivery of microvesicles carrying miR-155 to disease-prone regions of arteries provides a novel mechanism by which neutrophils contribute to vascular inflammation and atherogenesis.

scholarly journals Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ingrid Gomez ◽  
Ben Ward ◽  
Celine Souilhol ◽  
Chiara Recarti ◽  
Mark Ariaans ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Vascular Inflammation ◽  
Plaque Formation ◽  
Atherosclerotic Plaques ◽  
High Fat ◽  
Inflammatory Gene Expression ◽  
Disturbed Flow ◽  
Atherosclerotic Plaque Formation

AbstractNeutrophils are implicated in the pathogenesis of atherosclerosis but are seldom detected in atherosclerotic plaques. We investigated whether neutrophil-derived microvesicles may influence arterial pathophysiology. Here we report that levels of circulating neutrophil microvesicles are enhanced by exposure to a high fat diet, a known risk factor for atherosclerosis. Neutrophil microvesicles accumulate at disease-prone regions of arteries exposed to disturbed flow patterns, and promote vascular inflammation and atherosclerosis in a murine model. Using cultured endothelial cells exposed to disturbed flow, we demonstrate that neutrophil microvesicles promote inflammatory gene expression by delivering miR-155, enhancing NF-κB activation. Similarly, neutrophil microvesicles increase miR-155 and enhance NF-κB at disease-prone sites of disturbed flow in vivo. Enhancement of atherosclerotic plaque formation and increase in macrophage content by neutrophil microvesicles is dependent on miR-155. We conclude that neutrophils contribute to vascular inflammation and atherogenesis through delivery of microvesicles carrying miR-155 to disease-prone regions.

scholarly journals Maternal high-fat diet induces sex-specific changes to glucocorticoid and inflammatory signaling in response to corticosterone and lipopolysaccharide challenge in adult rat offspring

2019 ◽  
Author(s):  
Sanoji Wijenayake ◽  
Mouly F. Rahman ◽  
Christine M.W. Lum ◽  
Wilfred C. De Vega ◽  
Aya Sasaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
Inflammatory Responses ◽  
Physiological Stress ◽  
High Fat ◽  
Inflammatory Gene Expression ◽  
Inflammatory Genes ◽  
Inflammatory Gene ◽  
Rat Offspring

ABSTRACTBackgroundAcute elevations in endogenous corticosterone (CORT) with psychosocial stress or exogenous administration potentiate inflammatory gene expression. Maternal obesity as a result of high-fat diet (HFD) consumption has been linked to higher basal levels of neuroinflammation, including increased expression of pro-inflammatory genes in the amygdala. These findings suggest that exposure to maternal HFD may elicit pro-inflammatory responses in the presence of an immune stressor such as lipopolysaccharide (LPS), a component of gram-negative bacteria, as well as acute elevated CORT.MethodsRat offspring were exposed to maternal HFD or control diet (CHD) throughout pre and postnatal development until weaning, when all offspring were provided CHD until adulthood. In adulthood, offspring were ‘challenged’ with administration of exogenous CORT, to simulate an acute physiological stress, LPS, to induce an immune stress, or both. qPCR was used to measure transcript abundance of CORT receptors and downstream inflammatory genes in the amygdala, hippocampus and prefrontal cortex, brain regions that mediate neuroendocrine and behavioral responses to stress.ResultsHFD female offspring exhibited elevations in anti-inflammatory transcripts, whereas HFD male offspring responded with greater pro-inflammatory gene expression to simultaneous CORT and LPS administration.ConclusionsThese findings suggest that exposure to maternal HFD leads to sex-specific alterations that may alter inflammatory responses in the brain, possibly as an adaptive response to basal inflammation.

scholarly journals Dietary Sodium Nitrite Causes Similar Modifications to Splenic Inflammatory Gene Expression as a High-Fat Diet

2021 ◽  
Vol 67 (6) ◽  
pp. 404-416
Author(s):  
Motoko OARADA ◽  
Yuushi OKUMURA ◽  
Katsuya HIRASAKA ◽  
Kosuke SUGIURA ◽  
Nobuhiko TACHIBANA ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sodium Nitrite ◽  
High Fat Diet ◽  
Dietary Sodium ◽  
High Fat ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene

scholarly journals Novel interaction of antioxidant-1 with TRAF4: role in inflammatory responses in endothelial cells

2019 ◽  
Vol 317 (6) ◽  
pp. C1161-C1171
Author(s):  
Archita Das ◽  
Varadarajan Sudhahar ◽  
Masuko Ushio-Fukai ◽  
Tohru Fukai
Keyword(s):  
Endothelial Cells ◽  
High Fat Diet ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Dependent Manner ◽  
Oxygen Species ◽  
High Fat ◽  
Inflammatory Gene Expression ◽  
Tnf Α

NADPH oxidase (NOX)-derived reactive oxygen species (ROS) and copper (Cu), an essential micronutrient, have been implicated in vascular inflammatory diseases. We reported that in proinflammatory cytokine TNF-α-stimulated endothelial cells (ECs), cytosolic Cu chaperone antioxidant-1 (Atox1) functions as a Cu-dependent transcription factor for the NOX organizer p47phox, thereby increasing ROS-dependent inflammatory gene expression. However, the role and mechanism of Atox1 nuclear translocation in inflamed ECs remain unclear. Using enface staining and nuclear fractionation, here we show that Atox1 was localized in the nucleus in inflamed aortas from ApoE−/− mice with angiotensin II infusion on a high-fat diet, while it was found in cytosol in those from control mice. In cultured human ECs, TNF-α stimulation promoted Atox1 nuclear translocation within 15 min, which was associated with Atox1 binding to TNF-α receptor-associated factor 4 (TRAF4) in a Cu-dependent manner. TRAF4 depletion by siRNA significantly inhibited Atox1 nuclear translocation, p47phox expression, and ROS production as well as its downstream VCAM1/ICAM1 expression and monocyte adhesion to inflamed ECs, which were rescued by overexpression of nuclear targeted Atox1. Furthermore, Atox1 colocalized with TRAF4 at the nucleus in TNF-α-stimulated inflamed ECs and vessels. In summary, Cu-dependent Atox1 binding to TRAF4 plays an important role in Atox1 nuclear translocation and ROS-dependent inflammatory responses in TNF-α-stimulated ECs. Thus the Atox1-TRAF4 axis is a novel therapeutic target for vascular inflammatory disease such as atherosclerosis.

scholarly journals Maternal high-fat diet-induced programing of gut taste receptor and inflammatory gene expression in rat offspring is ameliorated by CLA supplementation

2015 ◽  
Vol 3 (10) ◽  
pp. e12588 ◽  
Author(s):  
Clare M. Reynolds ◽  
Stephanie A. Segovia ◽  
Xiaoyuan D. Zhang ◽  
Clint Gray ◽  
Mark H. Vickers
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Taste Receptor ◽  
High Fat ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Rat Offspring

scholarly journals Diabetic pregnancy as a novel risk factor for cardiac dysfunction in the offspring—the heart as a target for fetal programming in rats

Diabetologia ◽  
2021 ◽  
Author(s):  
Till Schütte ◽  
Sarah M. Kedziora ◽  
Nadine Haase ◽  
Florian Herse ◽  
Natalia Alenina ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factor ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Rat Model ◽  
Cardiac Dysfunction ◽  
High Fat Diet ◽  
Diabetic Pregnancy ◽  
Adult Offspring ◽  
High Fat

Abstract Aims/hypothesis The impact of diabetic pregnancy has been investigated extensively regarding offspring metabolism; however, little is known about the influence on the heart. We aimed to characterise the effects of a diabetic pregnancy on male adult offspring cardiac health after feeding a high-fat diet in an established transgenic rat model. Methods We applied our rat model for maternal type 2 diabetes characterised by maternal insulin resistance with hyperglycaemia and hyperinsulinaemia. Diabetes was induced preconceptionally via doxycycline-induced knock down of the insulin receptor in transgenic rats. Male wild-type offspring of diabetic and normoglycaemic pregnancies were raised by foster mothers, followed up into adulthood and subgroups were challenged by a high-fat diet. Cardiac phenotype was assessed by innovative speckle tracking echocardiography, circulating factors, immunohistochemistry and gene expression in the heart. Results When feeding normal chow, we did not observe differences in cardiac function, gene expression and plasma brain natriuretic peptide between adult diabetic or normoglycaemic offspring. Interestingly, when being fed a high-fat diet, adult offspring of diabetic pregnancy demonstrated decreased global longitudinal (−14.82 ± 0.59 vs −16.60 ± 0.48%) and circumferential strain (−23.40 ± 0.57 vs −26.74 ± 0.34%), increased relative wall thickness (0.53 ± 0.06 vs 0.37 ± 0.02), altered cardiac gene expression, enlarged cardiomyocytes (106.60 ± 4.14 vs 87.94 ± 1.67 μm), an accumulation of immune cells in the heart (10.27 ± 0.30 vs 6.48 ± 0.48 per fov) and higher plasma brain natriuretic peptide levels (0.50 ± 0.12 vs 0.12 ± 0.03 ng/ml) compared with normoglycaemic offspring on a high-fat diet. Blood pressure, urinary albumin, blood glucose and body weight were unaltered between groups on a high-fat diet. Conclusions/interpretation Diabetic pregnancy in rats induces cardiac dysfunction, left ventricular hypertrophy and altered proinflammatory status in adult offspring only after a high-fat diet. A diabetic pregnancy itself was not sufficient to impair myocardial function and gene expression in male offspring later in life. This suggests that a postnatal high-fat diet is important for the development of cardiac dysfunction in rat offspring after diabetic pregnancy. Our data provide evidence that a diabetic pregnancy is a novel cardiac risk factor that becomes relevant when other challenges, such as a high-fat diet, are present. Graphical abstract

Sign in / Sign up

Export Citation Format

Share Document