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.

Overexpression of human heme oxygenase-1 attenuates endothelial cell sloughing in experimental diabetes

2004 ◽  
Vol 287 (6) ◽  
pp. H2468-H2477 ◽  
Author(s):  
Nader G. Abraham ◽  
Rita Rezzani ◽  
Luigi Rodella ◽  
Adam Kruger ◽  
Derek Taller ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Heme Oxygenase ◽  
Defense Mechanism ◽  
Cell Damage ◽  
Vascular Complications ◽  
Diabetic Rats ◽  
Circulating Endothelial Cells ◽  
Heme Oxygenase 1 ◽  
Cell Physiology

Heme oxygenase (HO)-1 represents a key defense mechanism against oxidative injury. Hyperglycemia produces oxidative stress and various perturbations of cell physiology. The effect of streptozotocin (STZ)-induced diabetes on aortic HO activity, heme content, the number of circulating endothelial cells, and urinary 8-epi-isoprostane PGF2α(8-Epi) levels in control rats and rats overexpressing or underexpressing HO-1 was measured. HO activity was decreased in hyperglycemic rats. Hyperglycemia increased urinary 8-Epi, and this increase was augmented in rats underexpressing HO-1 and diminished in rats overexpressing HO-1. The number of detached endothelial cells and O2−formation increased in diabetic rats and in hyperglycemic animals underexpressing HO-1 and decreased in diabetic animals overexpressing HO-1 compared with controls. These data demonstrate that HO-1 gene transfer in hyperglycemic rats brings about a reduction in O2−production and a decrease in endothelial cell sloughing. Upregulation of HO-1 decreases oxidant production and endothelial cell damage and shedding and may attenuate vascular complications in diabetes.

scholarly journals Crocodile blood supplementation protects vascular function in diabetic mice

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Chui Yiu Bamboo Chook ◽  
Francis M. Chen ◽  
Gary Tse ◽  
Fung Ping Leung ◽  
Wing Tak Wong
Keyword(s):  
Endothelial Cells ◽  
Vascular Function ◽  
Quantitative Polymerase Chain Reaction ◽  
Functional Study ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Gene Expressions ◽  
Inflammatory State ◽  
Crocodile Blood

Abstract Cardiovascular disease is a major cause of mortality in diabetic patients due to the heightened oxidative stress and pro-inflammatory state in vascular tissues. Effective approaches targeting cardiovascular health for diabetic patients are urgently needed. Crocodile blood, an emerging dietary supplement, was suggested to have anti-oxidative and anti-inflammatory effects in vitro, which have yet to be proven in animal models. This study thereby aimed to evaluate whether crocodile blood can protect vascular function in diabetic mice against oxidation and inflammation. Diabetic db/db mice and their counterparts db/m+ mice were treated daily with crocodile blood soluble fraction (CBSF) or vehicle via oral gavage for 4 weeks before their aortae were harvested for endothelium-dependent relaxation (EDR) quantification using wire myograph, which is a well-established functional study for vascular function indication. Organ culture experiments culturing mouse aortae from C57BL/6 J mice with or without IL-1β and CBSF were done to evaluate the direct effect of CBSF on endothelial function. Reactive oxygen species (ROS) levels in mouse aortae were assessed by dihydroethidium (DHE) staining with inflammatory markers in endothelial cells quantified by quantitative polymerase chain reaction (qPCR). CBSF significantly improved deteriorated EDR in db/db diabetic mice through both diet supplementation and direct culture, with suppression of ROS level in mouse aortae. CBSF also maintained EDR and reduced ROS levels in mouse aortae against the presence of pro-inflammatory IL-1β. Under the pro-inflammatory state induced by IL-1β, gene expressions of inflammatory cytokines were downregulated, while the protective transcripts UCP2 and SIRT6 were upregulated in endothelial cells. Our study suggests a novel beneficial effect of crocodile blood on vascular function in diabetic mice and that supplementation of diet with crocodile blood may act as a complementary approach to protect against vascular diseases through anti-oxidation and anti-inflammation in diabetic patients. Graphical abstract

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.

Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells

Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3465-3473 ◽  
Author(s):  
Shane C. McAllister ◽  
Scott G. Hansen ◽  
Rebecca A. Ruhl ◽  
Camilo M. Raggo ◽  
Victor R. DeFilippis ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Heme Oxygenase ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Kaposi Sarcoma ◽  
Heme Oxygenase 1 ◽  
Spindle Cell Proliferation

Abstract Kaposi sarcoma (KS) is the most common AIDS-associated malignancy and is characterized by angiogenesis and the presence of spindle cells. Kaposi sarcoma-associated herpesvirus (KSHV) is consistently associated with all clinical forms of KS, and in vitro infection of dermal microvascular endothelial cells (DMVECs) with KSHV recapitulates many of the features of KS, including transformation, spindle cell proliferation, and angiogenesis. To study the molecular mechanisms of KSHV pathogenesis, we compared the protein expression profiles of KSHV-infected and uninfected DMVECs. This comparison revealed that heme oxygenase-1 (HO-1), the inducible enzyme responsible for the rate-limiting step in heme catabolism, was up-regulated in infected endothelial cells. Recent evidence suggests that the products of heme catabolism have important roles in endothelial cell biology, including apoptosis and angiogenesis. Here we show that HO-1 mRNA and protein are up-regulated in KSHV-infected cultures. Comparison of oral and cutaneous AIDS-KS tissues with normal tissues revealed that HO-1 mRNA and protein were also up-regulated in vivo. Increased HO-1 enzymatic activity in vitro enhanced proliferation of KSHV-infected DMVECs in the presence of free heme. Treatment with the HO-1 inhibitor chromium mesoporphyrin IX abolished heme-induced proliferation. These data suggest that HO-1 is a potential therapeutic target for KS that warrants further study. (Blood. 2004;103: 3465-3473)

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.

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