Articolele autorului Radu Daniel Rudic
Link la profilul stiintific al lui Radu Daniel Rudic

Human T cells infiltrate and injure pig coronary artery grafts with activated but not quiescent endothelium in immunodeficient mouse hosts

BACKGROUND: We have previously demonstrated that human artery grafts transplanted to immunodeficient mice are infiltrated and injured by unsensitized allogeneic human T cells. We extended our investigations to human anti-porcine xenoresponses in this model. METHODS: Pig coronary artery segments were interposed into the infrarenal aorta of severe combined immunodeficiency/beige mice. After 7 days, certain recipients were reconstituted with human leukocytes

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Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock

Circadian clock genes are expressed in the suprachiasmatic nucleus and in peripheral tissues to regulate cyclically physiological processes. Synchronization of peripheral oscillators is thought to involve humoral signals, but the mechanisms by which these are mediated and integrated are poorly understood. We report a hormone-dependent interaction of the nuclear receptors, RAR alpha and RXR alpha, with CLOCK and MOP4. These interactions negatively

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Functional reconstitution of endothelial nitric oxide synthase reveals the importance of serine 1179 in endothelium-dependent vasomotion

Phosphorylation of endothelial nitric oxide synthase (eNOS) at serine 1179 can activate the enzyme, leading to NO release. Because eNOS is important in regulating vascular tone, we investigated whether phosphorylation of this residue is involved in vasomotion. Adenoviral transduction of endothelial cells (ECs) with the phosphomimetic S1179DeNOS markedly increased basal and vascular endothelial cell growth factor (VEGF)-stimulated NO release compared

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Nitric oxide-releasing aspirin decreases vascular injury by reducing inflammation and promoting apoptosis

Endothelial dysfunction, defined as a deficit in the bioavailability of nitric oxide (NO), occurs as sequelae of many vascular diseases; however, the utility of supplementing NO to obviate the extent of disease is understudied. Here, we examined if prolonged treatment with an NO-releasing form of aspirin (NO-ASA) can influence neointimal remodeling of femoral arteries of hypercholesterolemic ApoE (-/-) mice. Treatment of ApoE (-/-) mice with NO-ASA,

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Histone acetyltransferase-dependent chromatin remodeling and the vascular clock

Rhythmic gene expression is central to the circadian control of physiology in mammals. Transcriptional activation of Per and Cry genes by heterodimeric bHLH-PAS proteins is a key event in the feedback loop that drives rhythmicity; however, the mechanism is not clearly understood. Here we show the transcriptional coactivators and histone acetyltransferases, p300/CBP, PCAF, and ACTR associate with the bHLH-PAS proteins, CLOCK and NPAS2, to regulate

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A functional genomics strategy reveals Rora as a component of the mammalian circadian clock

The mammalian circadian clock plays an integral role in timing rhythmic physiology and behavior, such as locomotor activity, with anticipated daily environmental changes. The master oscillator resides within the suprachiasmatic nucleus (SCN), which can maintain circadian rhythms in the absence of synchronizing light input. Here, we describe a genomics-based approach to identify circadian activators of Bmal1, itself a key transcriptional activator

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BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis

Circadian timing is generated through a unique series of autoregulatory interactions termed the molecular clock. Behavioral rhythms subject to the molecular clock are well characterized. We demonstrate a role for Bmal1 and Clock in the regulation of glucose homeostasis. Inactivation of the known clock components Bmal1 (Mop3) and Clock suppress the diurnal variation in glucose and triglycerides. Gluconeogenesis is abolished by deletion of Bmal1 and

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Peripheral clocks and the regulation of cardiovascular and metabolic function

Circadian rhythms generated by cell autonomous biological clocks allow for the appropriate temporal synchronization of physiology and behavior, optimizing the efficiency of biological systems. Circadian oscillators and functions have been uncovered in both central and peripheral tissues. This article describes methodology, experimental design, and technical challenges pertaining to studies of circadian rhythms in the periphery. Experimental approaches

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COX-2-derived prostacyclin modulates vascular remodeling

Suppression of prostacyclin (PGI2) biosynthesis may explain the increased incidence of myocardial infarction and stroke which has been observed in placebo controlled trials of cyclooxygenase (COX)-2 inhibitors. Herein, we examine if COX-2-derived PGI2 might condition the response of the vasculature to sustained physiologic stress in experimental models that retain endothelial integrity. Deletion of the PGI2 receptor (IP) or suppression of PGI2 with

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Bioinformatic analysis of circadian gene oscillation in mouse aorta

BACKGROUND: Circadian rhythmicity of many aspects of cardiovascular function-blood pressure, coagulation and contractile function-is well established, as is diurnal variation in important clinical events, such as myocardial infarction and stroke. Here, we undertake studies to globally assess circadian gene expression in murine aorta. METHODS AND RESULTS: Aortae from mice were harvested at 4-hour intervals for 2 circadian cycles (48 hours). Gene expression

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