Heme Oxygenase-1

Stocker, Roland; Perrella, Mark A.

doi:10.1161/circulationaha.105.598698

Cited by 197 publications

(107 citation statements)

References 135 publications

(171 reference statements)

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“…with increase of expression of EC-SOD, cytosolic dimeric Cu,Zn-SOD (SOD-1), catalase (CAT), hemoxygenase-1. The later is the enzyme induced by the stress; it transforms hem in biliverdin (for its further metabolic transformation in bilirubin), and ions of iron [32,33]. The difficulties of clinical use of gene therapy are caused by limited duration of transgenic expression, but cardiovascular disorders (for example, atherosclerosis) develop during the decades, or, visa versa, occur spontaneously (plaque disruption, thrombosis).…”

Section: Experimental Study Of Antioxidant Gene Therapymentioning

confidence: 99%

Enzymatic Antioxidants: Next Phase of Pharmacological Effort to Fight Oxidative Stress?

Maksimenko¹,

Vavaev²,

Tischenko³

2010

TOPROCJ

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Abstract:The focus in the research of antioxidants is notably displaced in favour of research of enzyme derivatives. Extracellular superoxide dismutase (EC-SOD) is of the particular interest, as it demonstrates in vivo the protective action against development of atherosclerosis, hypertension, heart failure, diabetes mellitus. The reliable association of coronary artery disease with the decreased level of heparin-released EC-SOD was established in clinical researches. To base and develop antioxidant therapy, various SOD isozymes, catalase (CAT), the methods of experimental gene therapy, combined application of SOD-and CAT-activities are used. Covalent bienzyme SOD -CHS -CAT conjugate (where CHS -chondroitin sulphate) showed in the experimental trials its high efficacy as the antithrombotic agent. Pre-clinical research data approve the reliable option to gain for it the status of drug candidate. The trend to use the components of glycocalyx and extracellular matrix for target delivery of medical substances is evident. Development of new enzyme antioxidants for therapeutical destination is closely connected with becoming and progress of medical biotechnology, pharmaceutical industry, bioeconomy.

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Section: Experimental Study Of Antioxidant Gene Therapymentioning

confidence: 99%

Enzymatic Antioxidants: Next Phase of Pharmacological Effort to Fight Oxidative Stress?

Maksimenko¹,

Vavaev²,

Tischenko³

2010

TOPROCJ

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“…12 Upregulation of HO-1 protects against vascular diseases, including atherosclerosis via promoting re-endothelialization, inducing anti-inflammatory activities, inhibiting smooth-muscle-cell proliferation, regulating vascular tone and by increasing cellular antioxidant activities. 13 Recently, Wu et al 14 have linked the HO-1 induction effect on re-endothelialization to HO-1's ability to increase the numbers of circulating EPCs and bone marrow early and late outgrowth progenitor cells, and to enhance the maturation of bone marrow-derived progenitor cells.…”

Section: Introductionmentioning

confidence: 99%

Endothelial progenitor cells relationships with clinical and biochemical factors in a human model of blunted angiotensin II signaling

et al. 2011

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Angiotensin II (Ang II) is essential for endothelial progenitor cells (EPCs) function as Ang-II-induced oxidative stress causes senescence of EPCs and endothelial dysfunction and Ang II type 1 receptor blockers increase EPCs. Moreover, EPCs activity is dependent on nitric oxide (NO) and heme oxygenase (HO)-1 as these correlate with EPCs senescence and are reduced in hypertensives. Bartter's/Gitelman's syndrome patients (BS/GS), have increased Ang II yet normo/hypotension along with blunted Ang II signaling, reduced oxidative stress, increased NO and HO-1, thus presenting a unique system to explore EPC biology and its relationship with vascular clinical and biochemical correlates. Circulating EPCs, NO-dependent vasodilation (flow-mediated dilation (FMD)) and HO-1 gene expression were characterized in 10 BS/GS patients and in 10 normotensive subjects. EPCs defined by cell surface antigens CD34+kinase-insert domain receptor (KDR+), CD133+KDR+ and CD133+CD34+KDR+ cells were quantitiated via direct three-color flow-cytometry analysis, HO-1 gene expression by reverse transcription-PCR and FMD by B-mode echo scan of the right brachial artery. Correlation analysis was carried out regarding FMD and EPCs, FMD and HO-1 and EPCs and HO-1. In BS/GS, CD34+KDR+ cell numbers did not differ from controls while CD133+KDR+ and CD133+CD34+ KDR+ cell numbers were higher. HO-1 gene expression, as well as FMD, was higher in BS/GS compared with controls. Both CD133+KDR+ and CD133+CD34+KDR+ strongly correlated with both FMD and HO-1. FMD and HO-1 were also strongly correlated. These results document in a human system that EPC numbers and specific populations are related to important clinical and biochemical factors involved in cardiovascular (CV) status and reaffirm the utility of BS/GS patients as a useful system to investigate EPC's role(s) in the pathophysiology of cardiovascular remodeling in humans.

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“…Of note, several antioxidant genes such as extracellular superoxide dismutase and heme oxygenase-1 (HO-1) have been used for gene therapy in experimental animal models of CVD. 3 Heme oxygenase-1 has well-documented protective effects in the vasculature (reviewed in Stocker and Perrella 4 and Ryter et al 5 ). It is the rate-limiting enzyme of heme catabolism, in which heme is degraded to carbon monoxide (CO) and biliverdin.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress-inducible lentiviral vectors for gene therapy

Hurttila

Kansanen

et al. 2008

Gene Ther

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Oxidative stress is important in several pathologies, including cardiovascular diseases such as atherosclerosis and cardiac ischemia-reperfusion injury. An important mechanism for adaptation to oxidative stress is induction of genes through the antioxidant response element (ARE), which regulates the expression of antioxidant and cytoprotective genes via the transcription factor Nrf2 (nuclear factor E2-related factor 2). As Nrf2-regulated genes are induced during oxidant stress occurring, for example, in reperfusion after ischemia, we took a novel approach to exploit ARE for the development of oxidative stress-inducible gene therapy vectors. To this end, one, two or three ARE-containing regions from human NAD(P)H:quinone oxidoreductase-1, glutamate-cysteine ligase modifier subunit and mouse heme oxygenase-1 were cloned into a vector expressing luciferase under a minimal SV40 promoter. The construct, which was the most responsive to ARE-inducing agents, was chosen for further studies in which a lentiviral vector was produced for an efficient transfer to endothelial cells. Heme oxygenase-1 (HO-1), which has well-characterized anti-inflammatory properties, was used as the therapeutic transgene. In human endothelial cells, AREdriven HO-1 overexpression inhibited nuclear factor-kB activation and subsequent vascular cell adhesion molecule-1 expression induced by tumor necrosis factor-a. We conclude that the ARE element is a promising alternative for the development of oxidative stress-inducible gene therapy vectors.

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Heme Oxygenase-1

Cited by 197 publications

References 135 publications

Enzymatic Antioxidants: Next Phase of Pharmacological Effort to Fight Oxidative Stress?

Enzymatic Antioxidants: Next Phase of Pharmacological Effort to Fight Oxidative Stress?

Endothelial progenitor cells relationships with clinical and biochemical factors in a human model of blunted angiotensin II signaling

Oxidative stress-inducible lentiviral vectors for gene therapy

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