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.

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.

scholarly journals Targeting Heme Oxygenase-1 in Cardiovascular and Kidney Disease

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 181 ◽  
Author(s):  
Heather A. Drummond ◽  
Zachary L. Mitchell ◽  
Nader G. Abraham ◽  
David E. Stec
Keyword(s):  
Blood Pressure ◽  
Cardiovascular System ◽  
Heme Oxygenase ◽  
Critical Role ◽  
Organ Injury ◽  
Renal Diseases ◽  
Heme Oxygenase 1 ◽  
Benefit Patient ◽  
Regulation Of Blood Pressure

Heme oxygenase (HO) plays an important role in the cardiovascular system. It is involved in many physiological and pathophysiological processes in all organs of the cardiovascular system. From the regulation of blood pressure and blood flow to the adaptive response to end-organ injury, HO plays a critical role in the ability of the cardiovascular system to respond and adapt to changes in homeostasis. There have been great advances in our understanding of the role of HO in the regulation of blood pressure and target organ injury in the last decade. Results from these studies demonstrate that targeting of the HO system could provide novel therapeutic opportunities for the treatment of several cardiovascular and renal diseases. The goal of this review is to highlight the important role of HO in the regulation of cardiovascular and renal function and protection from disease and to highlight areas in which targeting of the HO system needs to be translated to help benefit patient populations.

Functional Expression of Human Heme Oxygenase-1 Gene in Renal Structure of Spontaneously Hypertensive Rats

2003 ◽  
Vol 228 (5) ◽  
pp. 454-458 ◽  
Author(s):  
Alvin I. Goodman ◽  
Shou Quan ◽  
Liming Yang ◽  
Arika Synghal ◽  
Nader G. Abraham
Keyword(s):  
Blood Pressure ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Rat Kidney ◽  
Functional Expression ◽  
Heme Oxygenase 1 ◽  
Thick Ascending Limb ◽  
Bile Pigments ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Heme oxygenase (HO), by catabolizing heme to bile pigments, regulates the levels and activity of cellular hemoprotein and HO activity. We examined the effect of delivery of the human HO-1 gene on cellular heme in renal tissue using a retroviral vector. We used a single intracardiac injection of the concentrated infectious viral particles in 5-day-old spontaneously hypertensive rats; 25 were transduced with empty vector and 25 were transduced with the human HO-1 gene. Functional expression of human and rat HO-1 was measured after 2 and 4 weeks. Reverse transcription polymerase chain reaction showed that human HO-1 mRNA was expressed as early as 2 weeks, with the highest levels in the kidney. Western blot analysis showed distribution of human HO-1 protein in rat kidney structures, predominantly in the thick ascending limb of the loop of Henle as well as in proximal tubules and preglomerular arterioles. These areas also demonstrated higher HO activity as measured by increased conversion of heme to bilirubin and carbon monoxide. Functional expression of the human HO-1 gene was associated with a decrease in blood pressure in 4- and 8-week-old spontaneously hypertensive rats. Compared with nontransduced rats, human HO-1 gene overexpression in transduced rats was associated with a 35% decrease in urinary 20-hydroxyeicosatetraenoic acid, a potent vasoconstrictor and an inhibitor of tubular Na+ transport, which may be related to the decrease in blood pressure.

Association of heme oxygenase-1 gene promoter polymorphism and blood pressure in an Iranian population

2014 ◽  
Vol 44 (9) ◽  
pp. 931-932 ◽  
Author(s):  
F. Haghdoost ◽  
S. H. Javanmard ◽  
K. Keyhanian ◽  
A. A. Samety ◽  
P. Loghmani ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heme Oxygenase ◽  
Gene Promoter ◽  
Promoter Polymorphism ◽  
Iranian Population ◽  
Heme Oxygenase 1 ◽  
Gene Promoter Polymorphism

scholarly journals Induction of heme oxygenase-1 by hypoxia and free radicals in human dermal fibroblasts

2000 ◽  
Vol 278 (1) ◽  
pp. C92-C101 ◽  
Author(s):  
Maria V. Panchenko ◽  
Harrison W. Farber ◽  
Joseph H. Korn
Keyword(s):  
Free Radicals ◽  
Free Radical ◽  
Heme Oxygenase ◽  
Iron Homeostasis ◽  
Dermal Fibroblasts ◽  
Skin Fibroblasts ◽  
Free Radical Scavengers ◽  
Radical Scavenger ◽  
Heme Oxygenase 1

Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme catabolism and presumably is involved in cellular iron homeostasis. It is induced by a variety of cellular stresses, including oxygen deprivation and free radical-mediated stress. We examined induction of HO-1 mRNA in skin fibroblasts and investigated the mechanism by which it occurs. Hypoxia did not appear to act via induction of oxygen free radicals: induction of HO-1 was not sensitive to the free radical scavenger GSH or other antioxidants. Moreover, hypoxia did not increase steady-state levels of free radicals generated by fibroblasts. In contrast, HO-1 induction by the oxidants, H2O2and carbonyl cyanide m-chlorophenylhydrazone (CCCP) was significantly attenuated in the presence of free radical scavengers. This correlated with increased levels of free radical production in fibroblasts treated with these oxidants. Iron depletion by desferrioxamine mesylate, a specific iron complexon, completely inhibited hypoxic stimulation of HO-1 but did not attenuate the effect of H2O2and CCCP on HO-1 mRNA. Addition of Fe2+, Fe3+, or holo-transferrin to fibroblasts increased levels of HO-1 mRNA. Treatment of cells with hypoxia, but not H2O2or an exogenous source of iron, significantly increased the half-life of HO-1 mRNA. The data suggest hypoxia regulates HO-1 gene expression by a specific posttranscriptional mechanism: stabilization of mRNA. Hypoxia has previously been shown to increase fibroblast collagen synthesis and is thought to play a role in pathogenesis of systemic sclerosis (SSc). Skin fibroblasts isolated from patients with SSc demonstrated significantly stronger induction of HO-1 by hypoxia than did fibroblasts from normal controls. We hypothesize that exposure of SSc fibroblasts to hypoxic conditions leads to in vivo selective proliferation of cells that adapt to hypoxia.

Role of heme oxygenase-1 in hypoxia-reoxygenation: requirement of substrate heme to promote cardioprotection

2001 ◽  
Vol 281 (5) ◽  
pp. H1976-H1984 ◽  
Author(s):  
Roberta Foresti ◽  
Helen Goatly ◽  
Colin J. Green ◽  
Roberto Motterlini
Keyword(s):  
Heme Oxygenase ◽  
Reactive Oxygen Species Generation ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Heme Oxygenase 1 ◽  
Bile Pigment ◽  
Activity Levels ◽  
Low Oxygen ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity

Heme oxygenase-1 (HO-1) catalyzes the enzymatic degradation of heme to carbon monoxide, bilirubin, and iron. All three products possess biological functions; bilirubin, in particular, is a potent free radical scavenger of which its antioxidant property is enhanced at low oxygen tension. Here, we investigated the effect of severe hypoxia and reoxygenation on HO-1 expression in cardiomyocytes and determined whether HO-1 and its product, bilirubin, have a protective role against reoxygenation damage. Hypoxia caused a time-dependent increase in both HO-1 expression and heme oxygenase activity, which gradually declined during reoxygenation. Reoxygenation of hypoxic cardiomyocytes produced marked injury; however, incubation with hemin or bilirubin during hypoxia considerably reduced the damage at reoxygenation. The protective effect of hemin is attributable to increased availability of substrate for heme oxygenase activity, because hypoxic cardiomyocytes generated very little bilirubin when incubated with medium alone but produced substantial bile pigment in the presence of hemin. Interestingly, incubation with hemin also maintained high heme oxygenase activity levels during the reoxygenation period. Reactive oxygen species generation was enhanced after hypoxia, and hemin and bilirubin were capable once again to attenuate this effect. These results indicate that the HO-1-bilirubin pathway can effectively defend hypoxic cardiomyocytes against reoxygenation injury and highlight the issue of heme availability in the cytoprotective action afforded by HO-1.

Transfer of the Human Heme Oxygenase-1 Gene Decreases Blood Pressure and Promotes Growth in Spontaneously Hypertensive Rats

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 730-730
Author(s):  
Hatem E Sabaawy ◽  
Fan Zhang ◽  
Alberto Nasjletti ◽  
Michal Laniado-Schwartzman ◽  
Nader G Abraham
Keyword(s):  
Blood Pressure ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Body Weight Gain ◽  
Retroviral Vector ◽  
Left Ventricular ◽  
Intraluminal Pressure ◽  
Heme Oxygenase 1 ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

P203 Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, free iron and carbon monoxide (CO). Both heme and CO have been implicated in the regulation of vascular tone. We report the successful cloning of the human HO-1 cDNA (HHO-1) into a LXSN retroviral vector (LSN-HHO-1). A single intra-left ventricular delivery of 1×10 10 pfu/ml of LSN-HHO-1 to 5-day-old spontaneously hypertensive rats (SHR; n = 32) resulted in extended expression of the human HO-1 (mRNA and protein) in several tissues, including the kidney, liver, spleen, lung, heart, brain and aorta. The expression of HHO-1 was associated with a 2-3 fold increase in HO activity in these tissues. Mean blood pressure (MBP) of SHR injected with LSN-HHO-1 was significantly lower than that of SHR injected with the control empty vector LXSN, by 4 weeks of age (144±4.6 mmHg vs 164.8±6.5 mmHg, n=32, * p <0.01). SHR treated with LSN-HHO-1 demonstrated a consistent reduction in MBP of ≈20 ± 4 mmHg when compared with the control LXSN injected SHR throughout the 20 weeks of the experiment. Administration of the HO inhibitor, stannic mesoporphyrin (Sn MP), to LSN-HHO-1-treated SHR resulted in a 15 to 18 mmHg rise of MBP, further suggesting that increased HO expression underlie, at least in part, the blood pressure lowering effect of LSN-HHO-1. Rats expressing HHO-1 showed significant reduction in the urinary excretion of the vasoconstrictor cytochrome P-450 arachidonate metabolite, 20-HETE. Moreover, gracilis muscle arterioles (≈ 55μm in diameter) isolated from HHO-1 transgenic SHR showed less contractile responses to increased intraluminal pressure than vessels isolated from LXSN-treated SHR; this effect was reversed by the addition of SnMP. Interestingly, HHO-1 transgenic rats showed significant proportionate increase in somatic growth, i.e., nose to tail length, fibula length and body weight gain. These studies demonstrate that delivery of the human HO-1 gene by a retroviral vector results in permanent expression of HHO-1, long-term reduction in blood pressure together with growth promoting activity in the SHR.

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