In the arterial circulation, regions of disturbed flow (DF), which are characterized by separation and transient vortices, susceptible to atherogenesis, whereas undisturbed laminar (UF) appear protected. Coordinated regulation gene expression endothelial cells (EC) may result in differing regional phenotypes that either favor or inhibit atherogenesis. Linearly amplified RNA from freshly isolated EC DF (inner aortic arch) UF (descending thoracic aorta) normal adult pigs was used profile...

High levels of triglyceride-rich lipoproteins (TGRLs) in blood are linked to development atherosclerosis, yet the mechanisms by which these particles initiate inflammation endothelium unknown. TGRL isolated from human plasma during postprandial state was examined for its capacity bind cultured aortic endothelial cells (HAECs) and alter acute inflammatory response tumor necrosis factor-alpha. HAECs were repetitively incubated with dietary freshly 2 hours per day 1 3 days mimic lipidemia....

Rationale: A high-fat diet accompanied by hypertriglyceridemia increases an individual’s risk for development of atherosclerosis. An early event in this process is monocyte recruitment through binding to vascular cell adhesion molecule 1 (VCAM-1) upregulated on inflamed arterial endothelium. Diets high polyunsaturated fatty acids (PUFAs) may provide athero-protection ameliorating effect. Objective: We investigated the acute regulation VCAM-1 expression human aortic endothelial cells (HAEC)...

Although mRNA amplification is necessary for microarray analyses from limited amounts of cells and tissues, the accuracy transcription profiles following has not been well characterized. We tested fidelity differential gene expression linear by T7-mediated in a well-established vitro model cytokine [tumor necrosis factor α (TNFα)]-stimulated human endothelial using filter arrays 13,824 cDNAs. Transcriptional generated amplified antisense RNA (aRNA) (from 100 ng total RNA, ∼1 mRNA) were...

ABSTRACT Objective : Atherosclerosis is a focal disease that develops at sites of low and oscillatory shear stress in arteries. This study aimed to understand how endothelial cells sense gradient fluid transduce signals regulate membrane expression cell adhesion molecules monocyte recruitment. Methods Human aortic were stimulated with TNF‐α simultaneously exposed linear increased from 0 16 dyne/cm 2 . Cell molecule activation NFκ B quantified by immunofluorescence microscopy resolution the...

Circulating triglyceride-rich lipoproteins (TGRL) from hypertriglyceridemic subjects exacerbate endothelial inflammation and promote monocyte infiltration into the arterial wall. We have recently reported that TGRL isolated human blood after a high-fat meal can elicit pro- or anti-atherogenic state in aortic cells (HAEC), defined as up- down-regulation of VCAM-1 expression response to tumor necrosis factor alpha (TNFα) stimulation, respectively. A direct correlation was found between...

Increased expression of vascular cell adhesion molecule (VCAM)-1 on the activated arterial endothelial (EC) surface critically contributes to atherosclerosis which may in part be regulated by epigenetic mechanisms. This study investigated whether and how clinically available histone deacetylases 1 2 (HDAC1/2) inhibitor drug Romidepsin epigenetically modulates VCAM-1 suppress atherosclerosis. Methods: was analyzed primary human aortic EC (HAEC) treated with or transfected HDAC1/2-targeting...

Abstract Atherosclerosis impacts arteries where disturbed blood flow renders the endothelium susceptible to inflammation. Cytokine activation of endothelial cells (EC) upregulates VCAM-1 receptors that target monocyte recruitment atherosusceptible regions. Endoplasmic reticulum (ER) stress elicits EC dysregulation in metabolic syndrome. We hypothesized ER plays a central role mechanosensing shear (SS) by signaling enhanced Aortic were stimulated with low-dose TNFα (0.3 ng/ml) microfluidic...

A rise in postprandial serum triglycerides (PP-sTG) can potentiate inflammatory responses vascular endothelial cells (ECs) and thus serves as an independent risk factor for predicting increased cardiovascular morbidity. We examined triglyceride-rich lipoproteins (PP-TGRLs) subjects ranging from normal to hypertriglyceridemic their capacity alter EC acute responses. Cultured human aortic ECs (HAECs) were conditioned with PP-TGRLs isolated at the peak after a moderately high-fat meal. VLDL...

Dyslipidemia is a primary risk factor for cardiovascular disease, but the specific mechanisms that determine localization of atherosclerotic plaques in arteries are not well defined. Triglyceride-rich lipoproteins (TGRL) isolated from human plasma after high-fat meal modulate TNF-α-induced VCAM-1 expression cultured aortic endothelial cells (HAECs) via an interferon regulatory (IRF)-1-dependent transcriptional mechanism. We examined whether fluid shear stress acts as mediator IRF-1-dependent...

Epoxyeicosatrienoic acids (EETs) are formed from the metabolism of arachidonic acid by cytochrome P450s. EETs promote angiogenesis linked to tumor growth in various cancer models that is attenuated vivo cyclooxygenase 2 (COX-2) inhibitors. This study further defines a role for COX-2 mediating endothelial EET promoting angiogenesis. Using human aortic cells (HAECs), we quantified 8,9-EET-induced tube formation and cell migration as indicators angiogenic potential presence absence inducer...

Abstract Elevated triglyceride-rich lipoproteins (TGRL) in circulation is a risk factor for atherosclerosis. TGRL from subjects consuming high saturated fat test meal elicited variable inflammatory response TNFα-stimulated endothelial cells (EC) that correlated strongly with the polyunsaturated fatty acid (PUFA) content. This study investigates how relative abundance of oxygenated metabolites PUFA, oxylipins, altered postprandially, and these changes promote inflammation. Human aortic EC...

Abstract Clinically used inhibitors of mammalian target rapamycin (mTOR) negatively impacts endothelial-dependent vasodilatation (EDD) through unidentified mechanisms. Here we show that either the endothelium-specific deletion Mtor to inhibit both mTOR complexes, or depletion Raptor Rictor disrupt mTORC1 mTORC2, causes impaired EDD, accompanied by reduced NO in serum mice. Consistently, inhibition decreases production human and mouse EC. Specifically, suppresses eNOS gene expression, due...

Atherosclerosis occurs preferentially at sites of disturbed blood flow despite the influence risk factors contributing to systemic inflammation. The receptor for advanced glycation endproducts (RAGE) is a prominent mediator inflammation in diabetes that upregulated atherosclerotic plaques. Our goal was elucidate role arterial hemodynamics regulation RAGE expression and activity. Endothelial elevated disturbance aortas healthy swine. To demonstrate direct physiological shear stress (SS)...

Endothelial up‐regulation of VCAM‐1 at susceptible sites in arteries modulates the recruitment efficiency inflammatory monocytes that initiates atherosclerotic lesion formation. We reported hydrodynamic shear stress (SS) mechanoregulates inflammation human aortic endothelial cells through endoplasmic reticulum (ER) via activation transcription factor x‐box binding protein 1 (XBP1). Here, a microfluidic flow channel produces linear gradient SS along continuous monolayer endothelium was used...

Reactive oxygen species (ROS) production is known to increase as a result of muscular contractile activity and this phenomenon may perturb the fine-controlled cellular redox homeostasis within cells tissues. We studied possible correlations between individual aerobic performance-related factors oxidative stress markers profile in serum thirty-five endurance male runners that experienced modified Bruce-based maximal graded exercise test. Our investigation assessed systemic levels...

Abstract Human induced pluripotent stem cells (hiPSCs) not only provide an abundant source of vascular for potential therapeutic applications in disease but also constitute excellent model understanding the mechanisms that regulate differentiation and functionality cells. Here, we reported myocyte enhancer factor 2C (MEF2C) transcription factor, any other members MEF2 family, was robustly upregulated during progenitors endothelial (ECs) from hiPSCs. Vascular growth factors (VEGF) strongly...

Increased expression of vascular cell adhesion molecule 1 (VCAM-1) on the aortic endothelium is an early marker atherogenesis, promoted in part by elevated levels inflammatory cytokines such as TNF-α. Mammalian target rapamycin (mTOR) a ubiquitous signaling that has been considered to contribute diverse cellular processes through mTOR complex (mTORC1) or 2 (mTORC2). This study aimed elucidate role TNF-α-induced VCAM-1 arterial endothelium. Primary human endothelial cells (HAECs) were treated...

Severely burned patients benefit from intensive insulin therapy (IIT) for tight glycemic control (TGC). The authors evaluated the clinical impact of automatic correction hematocrit and ascorbic acid interference bedside glucose monitoring performance in critically ill burn patients. two point-of-care systems (GMSs): 1) GMS1, an autocorrecting device, 2) GMS2, a noncorrecting device were compared. Sixty remnant arterial blood samples collected prospective observational study to evaluate...