scholarly journals Vasculitis, Atherosclerosis, and Altered HDL Composition in Heme-Oxygenase-1-Knockout Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Kazunobu Ishikawa ◽  
Mohamad Navab ◽  
Aldons J. Lusis
Keyword(s):  
Heme Oxygenase ◽  
Knockout Mice ◽  
Plasma Lipid ◽  
Heme Oxygenase 1 ◽  
Chow Diet ◽  
Lipid Hydroperoxides ◽  
Standard Chow Diet ◽  
Lower Body Weight ◽  
One Year ◽  
Plasma Lipid Peroxidation

To elucidate roles of heme oxygenase-1 (HO-1) in cardiovascular system, we have analyzed one-year-old HO-1-knockout mice. Homozygous HO-1-knockout mice had severe aortitis and coronary arteritis with mononuclear cellular infiltration and fatty streak formation even on a standard chow diet. Levels of plasma total cholesterol and HDL were similar among the three genotypes. However, homozygous HO-1-knockout mice had lower body weight and plasma triglyceride. HO-1-deficiency resulted in alteration of the composition of HDL. The ratio of apolipoprotein AI to AII in HO-1-knockout mice was reduced about 10-fold as compared to wild-type mice. In addition, paraoxonase, an enzyme against oxidative stress, was reduced less than 50% in HO-1-knockout mice. The knockout mice also exhibited significant elevation of plasma lipid hydroperoxides. This study using aged HO-1-knockout mice strengthened the idea that HO-1 functions to suppress systemic inflammation in artery wall and prevents plasma lipid peroxidation.

Heme Oxygenase-1 Inhibits Atherosclerotic Lesion Formation in LDL-Receptor Knockout Mice

2001 ◽  
Vol 88 (5) ◽  
pp. 506-512 ◽  
Author(s):  
Kazunobu Ishikawa ◽  
Daisuke Sugawara ◽  
Xu-ping Wang ◽  
Kazunori Suzuki ◽  
Hiroyuki Itabe ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Knockout Mice ◽  
Ldl Receptor ◽  
Atherosclerotic Lesion ◽  
Heme Oxygenase 1 ◽  
Lesion Formation ◽  
Ldl Receptor Knockout Mice ◽  
Atherosclerotic Lesion Formation

scholarly journals Preconditioning with soluble guanylate cyclase activation prevents postischemic inflammation and reduces nitrate tolerance in heme oxygenase-1 knockout mice

2013 ◽  
Vol 305 (4) ◽  
pp. H521-H532 ◽  
Author(s):  
Walter Z. Wang ◽  
Allan W. Jones ◽  
Meifang Wang ◽  
William Durante ◽  
Ronald J. Korthuis
Keyword(s):  
Heme Oxygenase ◽  
Guanylate Cyclase ◽  
Knockout Mice ◽  
Soluble Guanylate Cyclase ◽  
Ischemia Reperfusion ◽  
Late Phase ◽  
Nitrate Tolerance ◽  
Mesenteric Arteries ◽  
Heme Oxygenase 1 ◽  
Leukocyte Rolling

Previously we have shown that, unlike wild-type mice (WT), heme oxygenase-1 knockout (HO-1−/−) mice developed nitrate tolerance and were not protected from inflammation caused by ischemia-reperfusion (I/R) when preconditioned with a H2S donor. We hypothesized that stimulation (with BAY 41-2272) or activation (with BAY 60-2770) of soluble guanylate cyclase (sGC) would precondition HO-1−/− mice against an inflammatory effect of I/R and increase arterial nitrate responses. Intravital fluorescence microscopy was used to visualize leukocyte rolling and adhesion to postcapillary venules of the small intestine in anesthetized mice. Relaxation to ACh and BAY compounds was measured on superior mesenteric arteries isolated after I/R protocols. Preconditioning with either BAY compound 10 min (early phase) or 24 h (late phase) before I/R reduced postischemic leukocyte rolling and adhesion to sham control levels and increased superior mesenteric artery responses to ACh, sodium nitroprusside, and BAY 41-2272 in WT and HO-1−/− mice. Late-phase preconditioning with BAY 60-2770 was maintained in HO-1−/− and endothelial nitric oxide synthase knockout mice pretreated with an inhibitor (dl-propargylglycine) of enzymatically produced H2S. Pretreatment with BAY compounds also prevented the I/R increase in small intestinal TNF-α. We speculate that increasing sGC activity and related PKG acts downstream to H2S and disrupts signaling processes triggered by I/R in part by maintaining low cellular Ca2+. In addition, BAY preconditioning did not increase sGC levels, yet increased the response to agents that act on reduced heme-containing sGC. Collectively these actions would contribute to increased nitrate sensitivity and vascular function.

P0454 : An additional heme oxygenase-1 knockout increases maturation of dendritic cells and liver inflammation in Mdr2 knockout mice

2015 ◽  
Vol 62 ◽  
pp. S482-S483
Author(s):  
R. Barikbin ◽  
M. Sandmann ◽  
A. Quaas ◽  
K. Karimi ◽  
G. Sass ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Heme Oxygenase ◽  
Knockout Mice ◽  
Heme Oxygenase 1 ◽  
Liver Inflammation

Heme oxygenase 1 protects ethanol-administered liver tissue in  Aldh2 knockout mice

Alcohol ◽  
2016 ◽  
Vol 52 ◽  
pp. 49-54 ◽  
Author(s):  
Akiko Matsumoto ◽  
David Thompson ◽  
Ying Chen ◽  
Vasilis Vasiliou ◽  
Toshihiro Kawamoto ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Knockout Mice ◽  
Liver Tissue ◽  
Heme Oxygenase 1

scholarly journals Spontaneously diabetic Ins2+/Akita:apoE-deficient mice exhibit exaggerated hypercholesterolemia and atherosclerosis

2011 ◽  
Vol 301 (1) ◽  
pp. E145-E154 ◽  
Author(s):  
John Y. Jun ◽  
Zhexi Ma ◽  
Lakshman Segar
Keyword(s):  
Ldl Receptor ◽  
Plasma Lipid ◽  
Lipoprotein Metabolism ◽  
Hdl Cholesterol ◽  
Chow Diet ◽  
Akt Phosphorylation ◽  
Standard Chow Diet ◽  
Vldl Secretion ◽  
Triglyceride Content ◽  
Coronary Events

Type 1 diabetes (T1D) increases the risk of adverse coronary events. Among risk factors, dyslipidemia due to altered hepatic lipoprotein metabolism plays a central role in diabetic atherosclerosis. Nevertheless, the likely alterations in plasma lipid/lipoprotein profile remain unclear, especially in the context of spontaneously developed T1D and atherosclerosis. To address this question, we generated Ins2+/Akita:apoE−/− mouse by cross-breeding Ins2+/Akita mouse (which has Ins2 gene mutation, causing pancreatic β-cell apoptosis and insulin deficiency) with apoE−/− mouse. Ins2+/Akita:apoE−/− mice developed T1D spontaneously at 4–5 wk of age. At 25 wk of age and while on a standard chow diet, diabetic Ins2+/Akita:apoE−/− mice exhibited an approximately threefold increase in atherosclerotic plaque in association with an approximatelty twofold increase in plasma non-HDL cholesterol, predominantly in the LDL fraction, compared with nondiabetic controls. To determine factors contributing to the exaggerated hypercholesterolemia, we assessed hepatic VLDL secretion and triglyceride content, expression of hepatic lipoprotein receptors, and plasma apolipoprotein composition. Diabetic Ins2+/Akita:apoE−/− mice exhibited diminished VLDL secretion by ∼50%, which was accompanied by blunted Akt phosphorylation in response to insulin infusion and decreased triglyceride content in the liver. Although the expression of hepatic LDL receptor was not affected, there was a significant reduction in the expression of lipolysis-stimulated lipoprotein receptor (LSR) by ∼28%. Moreover, there was a marked decrease in plasma apoB-100 with a significant increase in apoB-48 and apoC-III levels. In conclusion, exaggerated hypercholesterolemia and atherosclerosis in spontaneously diabetic Ins2+/Akita:apoE−/− mice may be attributable to impaired lipoprotein clearance in the setting of diminished expression of LSR and altered apolipoprotein composition of lipoproteins.

scholarly journals Upregulation of Heme Oxygenase-1 in Response to Wild Thyme Treatment Protects against Hypertension and Oxidative Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Nevena Mihailovic-Stanojevic ◽  
Zoran Miloradović ◽  
Milan Ivanov ◽  
Branko Bugarski ◽  
Đurđica Jovović ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Resistance ◽  
Heme Oxygenase ◽  
Plasma Lipid ◽  
Inverse Correlation ◽  
Radical Scavenger ◽  
Heme Oxygenase 1 ◽  
Cardiovascular Morbidity And Mortality ◽  
Wild Thyme ◽  
A Chain

High blood pressure is the most powerful contributor to the cardiovascular morbidity and mortality, and inverse correlation between consumption of polyphenol-rich foods or beverages and incidence of cardiovascular diseases gains more importance. Reactive oxygen species plays an important role in the development of hypertension. We found that wild thyme (a spice plant, rich in polyphenolic compounds) induced a significant decrease of blood pressure and vascular resistance in hypertensive rats. The inverse correlation between vascular resistance and plasma heme oxygenase-1 suggests that endogenous vasodilator carbon monoxide generated by heme oxidation could account for this normalization of blood pressure. Next product of heme oxidation, bilirubin (a chain-breaking antioxidant that acts as a lipid peroxyl radical scavenger), becomes significantly increased after wild thyme treatment and induces the reduction of plasma lipid peroxidation in hypertensive, but not in normotensive rats. The obtained results promote wild thyme as useful supplement for cardiovascular interventions.

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