Ramesh Natarajan

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BACKGROUND & AIMS Nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) are associated with known triggers of the unfolded protein response (UPR). The aims were to (1) evaluate the activity of UPR in NAFL and NASH and (2) correlate expression of UPR pathways with liver histology. METHODS Messenger RNA (mRNA) and protein expression were(More)
BACKGROUND The most important determinant of longevity in pulmonary arterial hypertension is right ventricular (RV) function, but in contrast to experimental work elucidating the pathobiology of left ventricular failure, there is a paucity of data on the cellular and molecular mechanisms of RV failure. METHODS AND RESULTS A mechanical animal model of(More)
RATIONALE Most patients with pulmonary arterial hypertension (PAH) die from right heart failure. Beta-adrenergic receptor blockade reduces mortality by about 30% in patients with left-sided systolic heart failure, but is not used in PAH. OBJECTIVES To assess the effect of the adrenergic receptor blocker carvedilol on the pulmonary circulation and right(More)
Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting(More)
The CXC chemokine IL-8, which promotes adhesion, activation, and transmigration of polymorphonuclear neutrophils (PMN), has been associated with production of tissue injury in reperfused myocardium. Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric peptide that is a key regulator of genes such as heme oxygenase (HO)-1 expressed under hypoxic conditions.(More)
We have shown previously that bile acids can activate the JNK pathway and down-regulate cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the neutral pathway of bile acid biosynthesis. In this study, the mechanism(s) by which deoxycholic acid (DCA) activates the JNK pathway were examined. FAS receptor (FAS-R) and acidic sphingomyelinase(More)
The role of activator protein-1 (AP-1) in tumor necrosis factor-alpha (TNF-alpha)-induced interleukin-8 (IL-8) gene expression was evaluated. We showed that TNF-alpha activates AP-1 in the transformed endothelial cell line ECV304 by transient transfections of IL-8 promoter construct pGL-3BF(2). Mutation of either the AP-1 site or the NF-IL-6 site on the(More)
In patients with chronic obstructive pulmonary disease (COPD), histone deacetylase (HDAC) expression and activity are reduced in the lung tissue. However, whether HDAC activity controls the maintenance of the lung alveolar septal structures has not been investigated. To explore the consequences of HDAC inhibition and address the question of whether HDAC(More)
OBJECTIVE Sepsis-induced lung injury is a persisting clinical problem with no direct therapy. Recent work suggests that intravenously infused ascorbic acid improves the circulatory dysfunction of sepsis. We used a model of endotoxin-induced acute lung injury to determine whether parenteral ascorbic acid modulates the dysregulated proinflammatory,(More)
Hypoxia inducible factor-1 (HIF-1) regulates changes in transcription of key genes such as inducible NO synthase (iNOS) in hypoxic/ischemic environments. In normoxia, HIF-1 activation is controlled by HIF-1alpha-prolyl 4-hydroxylases, which target HIF-1alpha for ubiquitination and proteasomal degradation. We hypothesized that normoxic HIF-1 preservation(More)