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

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Philip Wenzel ◽  
Heidi Rossmann ◽  
Christian Müller ◽  
Sabine Kossmann ◽  
Canan Simsek ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Arterial Hypertension ◽  
Heme Oxygenase ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Isometric Tension ◽  
Health Study ◽  
Heme Oxygenase 1 ◽  
Frequency Pattern ◽  
Deficient Mice

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 the NADPH oxidase. When subjected to disease models of vascular dysfunction - angiotensin II-infusion (ATII, 0.1mg/kg/d for 7d), streptozotocin-induced diabetes mellitus and aging - HO-1 deficient mice showed an increased vascular dysfunction (shown by isometric tension studies) that was inversely correlated with HO activity. In a primary prevention population based cohort (the Gutenberg Health Study, GHS), we assessed length polymorphisms of the HO-1 promoter region, established a bipolar frequency pattern of allele length (long vs short repeats) in 4937 individuals and found a moderately significant association with flow mediated dilation of the brachial artery (FMD) in individuals with arterial hypertension. Monocytic HO-1 mRNA expression was positively correlated with CD14 expression indicating proinflammatory monocytes (p<0.001) and inversely with FMD in 733 hypertensive individuals of the GHS. ATII-infused HO-1+/+ mice had a significant infiltration of proinflammatory CD11b+Ly6Chi monocytes into the aortic wall, which was sharpely increased in HO-1+/- and HO-1-/- mice, providing a mechanistic link of the monocyte phenotype determined by HO-1 and vascular dysfunction in arterial hypertension. Conclusions: We here present evidence that HO activity and expression and inversely correlates with vascular dysfunction and NADPH oxidase mediated oxidative stress in mice and humans. We conclude, that HO-1 is a regulator of vascular function in hypertension via determining the phenotype of inflammatory circulating and infiltrating monocytes.

scholarly journals Vascular function and arginine and dimethylarginines in gentamicin-induced renal failure: a possible effect of heme oxygenase 1 inducer hemin

2017 ◽  
Vol 95 (12) ◽  
pp. 1406-1413 ◽  
Author(s):  
Esra Aycan-Ustyol ◽  
Merve Kabasakal ◽  
Seldag Bekpinar ◽  
F. Ilkay Alp-Yıldırım ◽  
Ozge Tepe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Vascular Function ◽  
Asymmetric Dimethylarginine ◽  
Vascular Dysfunction ◽  
Cardiovascular Complication ◽  
Heme Oxygenase 1 ◽  
Antioxidant Enzyme Activities ◽  
Symmetric Dimethylarginine ◽  
Inflammatory Changes

Increased oxidative stress and disturbance in nitric oxide bioavailability lead to endothelial dysfunction and cardiovascular complication in renal disease. Gentamicin (GM), a commonly used antibiotic, exhibits a toxic effect on renal proximal tubules. Prevention of its nephrotoxicity is important. Therefore, we investigated whether heme oxygenase 1 HO-1) induction influenced kidney and vascular function in GM-administered rats. GM (100 mg·kg–1·day–1; i.p.) was given to rats alone or together with hemin (20 mg·kg–1 on alternate days; i.p.) for 14 days. Plasma and kidney l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) as well as kidney 4-hydroxynonenal (HNE) levels and myeloperoxidase (MPO) activity were measured. Histopathological examinations of kidney and relaxation and contraction responses of aorta were also examined. GM increased serum SDMA, urea nitrogen (BUN), and creatinine levels and caused histopathological alterations in the kidney. GM elevated HO-1 protein and mRNA expressions, 4-HNE level, and MPO activity and decreased antioxidant enzyme activities and l-arginine levels in the kidney. Decreased relaxation and contraction were detected in the aorta. Hemin restored renal oxidative stress and inflammatory changes together with vascular dysfunction, but did not affect SDMA, BUN, or creatinine levels. We conclude that HO-1 induction may be effective in improving renal oxidative stress, inflammation, and vascular dysfunction mediated by GM.

scholarly journals 323: Pravastatin improves pregnancy outcome and placental development in heme oxygenase-1 deficient mice

2018 ◽  
Vol 218 (1) ◽  
pp. S202-S203
Author(s):  
Abraham Tsur ◽  
Flora Kalish ◽  
Jordan Burgess ◽  
Hui Zhao ◽  
Kerriann Casey ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Placental Development ◽  
Deficient Mice

scholarly journals Splenic Ly6Chi monocytes contribute to adverse late post-ischemic left ventricular remodeling in heme oxygenase-1 deficient mice

2017 ◽  
Vol 112 (4) ◽  
Author(s):  
Mateusz Tomczyk ◽  
Izabela Kraszewska ◽  
Krzysztof Szade ◽  
Karolina Bukowska-Strakova ◽  
Marco Meloni ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Heme Oxygenase 1 ◽  
Deficient Mice

scholarly journals Inhibition of the NADPH oxidase regulates heme oxygenase 1 expression in chronic myeloid leukemia

Cancer ◽  
2011 ◽  
Vol 118 (13) ◽  
pp. 3433-3445 ◽  
Author(s):  
Melissa M. Singh ◽  
Mary E. Irwin ◽  
Yin Gao ◽  
Kechen Ban ◽  
Ping Shi ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Nadph Oxidase ◽  
Heme Oxygenase ◽  
Myeloid Leukemia ◽  
Heme Oxygenase 1

Abstract 386: Body Mass Index Exacerbates the Hypertension Mediated Increase in Endothelial Cell Sloughing and Suppression of Antioxidant Heme Oxygenase-1

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Ryan Stone ◽  
David Chaffin ◽  
David Jude ◽  
Zeid Khitan ◽  
Dong Hyun Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Cytokines ◽  
Heme Oxygenase ◽  
Vascular Function ◽  
Circulating Endothelial Cells ◽  
Heme Oxygenase 1 ◽  
Diabetic Patients ◽  
Obese Patients ◽  
Contributing Factors ◽  
Hypertensive Patients

Introduction: Endothelial Progenitor cells (EPCs) are bone marrow derived cells that migrate and differentiate into mature endothelial cells and play a significant role in the re-endothelialization and neovascularization of injured endothelium and restoration of vascular function. We examined whether obesity and hypertension exacerbates the levels of biomarkers including circulating endothelial cells (CEC), serum inflammatory cytokines, and the levels of heme oxygenase -1 (HO-1) in EPC. Methods: Peripheral blood from 10 normal, 15 obese, 12 hypertensive, 20 obese-hypertensive and 15 diabetic patients was analyzed for inflammatory cytokines, CEC number, adiponectin and HO-1 levels. Results: The levels of inflammatory cytokines increased with BMI and directly correlated with increasing obesity. Similarly, hypertensive patients have elevated CEC which are further increased in obese hypertensive patients (p<.05). HO-1 was reduced (p<.05) in both hypertensive and obese patients when compared to control. Similarly serum adiponectin levels were lower in hypertensive obese patients when compared to controls (p<.01). Inflammatory cytokines IL-1, IL-6, MCP-1 and TNFα were elevated in obese hypertensive patients compared to non-obese hypertensive patients (p<.05). Conclusion: We demonstrated in hypertension patients that obesity exacerbates vascular dysfunction and increases circulating endothelial cells and inflammatory cytokines. A reduction in the levels of HO-1 and adiponectin imply reduced antioxidant levels which are contributing factors towards vascular and adipocyte dysfunction in hypertension patients. Thus upregulation of HO-1 offers a potential therapeutic approach in the treatment of this population.

scholarly journals Characterization of hepatic macrophages and evaluation of inflammatory response in heme oxygenase-1 deficient mice exposed to scAAV9 vectors

PLoS ONE ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. e0240691
Author(s):  
Mateusz Tomczyk ◽  
Izabela Kraszewska ◽  
Robert Mąka ◽  
Agnieszka Waligórska ◽  
Józef Dulak ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Hepatic Macrophages ◽  
Deficient Mice

scholarly journals Exacerbation of Neonatal Hemolysis and Impaired Renal Iron Handling in Heme Oxygenase 1-Deficient Mice

2020 ◽  
Vol 21 (20) ◽  
pp. 7754
Author(s):  
Aleksandra Bednarz ◽  
Paweł Lipiński ◽  
Rafał R. Starzyński ◽  
Mateusz Tomczyk ◽  
Izabela Kraszewska ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Neonatal Period ◽  
Transient State ◽  
The Body ◽  
Heme Oxygenase 1 ◽  
Iron Species ◽  
Renal Epithelium ◽  
Molecular Machinery ◽  
Iron Retention ◽  
Deficient Mice

In most mammals, neonatal intravascular hemolysis is a benign and moderate disorder that usually does not lead to anemia. During the neonatal period, kidneys play a key role in detoxification and recirculation of iron species released from red blood cells (RBC) and filtered out by glomeruli to the primary urine. Activity of heme oxygenase 1 (HO1), a heme-degrading enzyme localized in epithelial cells of proximal tubules, seems to be of critical importance for both processes. We show that, in HO1 knockout mouse newborns, hemolysis was prolonged despite a transient state and exacerbated, which led to temporal deterioration of RBC status. In neonates lacking HO1, functioning of renal molecular machinery responsible for iron reabsorption from the primary urine (megalin/cubilin complex) and its transfer to the blood (ferroportin) was either shifted in time or impaired, respectively. Those abnormalities resulted in iron loss from the body (excreted in urine) and in iron retention in the renal epithelium. We postulate that, as a consequence of these abnormalities, a tight systemic iron balance of HO1 knockout neonates may be temporarily affected.

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