Search results for "NADP"

Lysine triggers apoptosis through a NADPH oxidase-dependent mechanism in human renal tubular cells

2012

Progressive chronic kidney disease (CKD) is common in lysinuric protein intolerance (LPI), a primary inherited aminoaciduria characterized by massive Lysine excretion in urine. However, by which mechanisms Lysine may cause kidney damage to tubule cells is still not understood. This study determined whether Lysine overloading of human proximal tubular cells (HK-2) in culture enhances apoptotic cell loss and its associated mechanisms. Overloading HK-2 with Lysine levels reproducing those observed in urine of patients affected by LPI (10 mM) increased apoptosis (+30%; p < 0.01 vs.C), as well as Bax and Apaf-1 expressions (+30-50% p < 0.05), while downregulated Bcl-2 (-40% p < 0.05). Apoptosis …

Endotheliale Dysfunktion: Pathophysiologie, Diagnostik und prognostische Bedeutung

2008

The endothelium plays a crucial role in the regulation of vascular tone. Recent studies have indicated that endothelial dysfunction develops in the presence of cardiovascular risk factors such as hypertension, diabetes mellitus, hypercholesterolemia and in chronic smokers, as well as in patients with a family history of cardiovascular disease. It has now been established that endothelial dysfunction represents the first indicator of vascular damage. Endothelial function can be assessed in coronary and peripheral conductance and resistance vessels by means of invasive and noninvasive (ultrasound-guided) methods such as intracoronary infusion of acetylcholine, the endothelium-dependent vasodi…

Nitric Oxide Synthesis in Vascular Physiology and Pathophysiology

2015

Nitric oxide (NO) is produced by three NO synthase (NOS) isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). Under physiological conditions, vascular NO is produced by eNOS and nNOS, with both playing atheroprotective roles. Under pathological conditions, iNOS can be induced and eNOS may become uncoupled. iNOS produces a large amount of NO, induces vascular dysfunction, and promotes atherogenesis. Uncoupled eNOS generates superoxide instead of NO and contributes significantly to endothelial dysfunction and atherogenesis. Major mechanisms of eNOS uncoupling include depletion of tetrahydrobiopterin, an essential co-factor for the eNOS enzyme, and deficiency of L-a…

Abstract 18540: Heme Oxygenase 1 Activity and Expression Suppresses a Proinflammatory Phenotype in Monocytes and Correlates With Endothelial Function…

2014

Background: Heme oxygenase-1 (HO-1) confers protection to the vasculature and suppresses inflammatory properties of monocytes and macrophages. It is unclear how HO-1 activity and expression determine the extent of vascular dysfunction in mice and humans. Methods and results: Decreasing HO activity was parallelled by decreasing aortic HO-1, eNOS and phospho-eNOS (ser1177) protein expression in HO-1 deficient mice, whereas aortic expression of nox2 showed a stepwise increase in HO-1+/- and HO-1-/- mice as compared to HO-1+/+ controls. Aortic superoxide formation increased depending on the extent of HO-1 deficiency and was blunted by the PKC inhibitor chelerythrine, indicating activation of t…

NADPH Oxidase Accounts for Enhanced Superoxide Production and Impaired Endothelium-Dependent Smooth Muscle Relaxation in BKβ1 −/− Mice

2006

Objective— Nitric oxide (NO)-induced vasorelaxation involves activation of large conductance Ca 2+ -activated K + channels (BK). A regulatory BKβ1 subunit confers Ca 2+ , voltage, and NO/cGMP sensitivity to the BK channel. We investigated whether endothelial function and NO/cGMP signaling is affected by a deletion of the β1-subunit. Methods and Results— Vascular superoxide in BKβ1 −/− was measured using the fluorescent dye hydroethidine and lucigenin-enhanced chemiluminescence. Vascular NO formation was analyzed using electron paramagnetic resonance (EPR), expression of NADPH oxidase subunits, the endothelial NO synthase (eNOS), the soluble guanylyl cyclase (sGC), as well as the activity a…

Age-related changes in cholesterol metabolism in macrosomic offspring of rats with streptozotocin-induced diabetes.

2001

The aim of this study was to determine the impact of diabetic macrosomia on cholesterol and lipoprotein metabolism. Age-related changes in the activities of serum LCAT, hepatic HMG-CoA reductase, cholesterol 7α-hydroxylase, and ACAT, the major enzymes involved in cholesterol metabolism, were determined in macrosomic offspring of streptozotocin-induced diabetic rats. Hepatic, serum, and lipoprotein cholesterol contents were also examined. Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, macrosomic pups had higher serum, LDL-HDL1, and H…

Combined sub-optimal doses of Rosuvastatin and Bexarotene impairs angiotensin II-induced arterial mononuclear cell adhesion through inhibition of Nox…

2015

Aim: Mononuclear cell (MC) infiltration into the arterial subendothelium is a key event in atherogenesis. Rosuvastatin (Rosu) and bexarotene (Bex) exert anti-inflammatory activity, but serious dose-related adverse effects have emerged. The need for safer and effective strategies to prevent and treat atherosclerosis led us to test the effect of combined use of both drugs on angiotensin II (Ang-II)-induced arterial MC recruitment. Results: Vehicle, Rosu (10–30 nM), Bex (0.3–1 μM), or a combination of both were administered to human umbilical arterial endothelial cells (HUAECs) 20 h before stimulation with 1 μM Ang-II (4 h). Surprisingly, a combination of Rosu (10 nM)+Bex (0.3 μM), which did n…

Is oxidative stress a therapeutic target in cardiovascular disease?

2010

An abnormal production of reactive oxygen species (ROS) and the subsequent decrease in vascular bioavailability of nitric oxide (NO) have long been proposed to be the common pathogenetic mechanism of the endothelial dysfunction, resulting from diverse cardiovascular risk factors such as hypercholesterolaemia, diabetes mellitus, chronic smoking, metabolic syndrome, and hypertension. Superoxide produced by the nicotinamide dinucleotide phosphate (NADPH) oxidase, mitochondrial sources, or the xanthine oxidase may react with NO, thereby resulting in excessive formation of peroxynitrite, a reactive nitrogen species that has been demonstrated to accelerate the atherosclerotic process by causing d…

Long-term cardiovascular risk of e-cigarettes

2020

Protein kinase C-inhibiting properties of the losartan metabolite EXP3179 make the difference.

2009

The inhibition of the renin-angiotensin axis with the angiotensin II (ATII) receptor blockers, such as losartan, candesartan, and valsartan, has been demonstrated, similar to angiotensin-converting enzyme inhibitors, to reduce mortality in patients with arterial hypertension, chronic congestive heart failure, and acute myocardial infarction.1 Initially, the ATII receptor antagonist losartan helped to demonstrate new classes of ATII receptors and substantially expanded our knowledge about the cardiovascular effects of the renin-angiotensin-aldosterone system and its effector peptide ATII. Researchers dealing with this compound soon revealed that, beyond its antihypertensive effects attribute…