Protection against ischemia/reperfusion injury and myocardial dysfunction by antisense-oligodeoxynucleotide directed at angiotensin-converting enzyme mRNA

Chen, H; Mohuczy, Dagmara; Li, D; Kimura, Birgitta; Phillips, M. Ian; Mehta, Puja K.; Mehta, Jawahar L.

doi:10.1038/sj.gt.3301439

Cited by 17 publications

(5 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This hypoxia sensitive vector could be used with genes that have proven beneficial effects in ischemia, such as superoxide dismutase, 21,22 heme oxygenase, 23 and antisenses to angiotensin II type 1 receptor, 24 ␤-1 adrenergic receptor, 25 and angiotensin-converting enzyme. 26 …”

Section: Tang Et Al Hypoxia Inducible Vector For Ischemiamentioning

confidence: 99%

Hypoxia Inducible Double Plasmid System for Myocardial Ischemia Gene Therapy

et al. 2002

View full text Add to dashboard Cite

Abstract-Coronary artery disease frequently involves repeated bouts of myocardial ischemia. To automatically up-regulate the cardioprotective transgenes under hypoxic ischemia, a "vigilant vector" gene therapy system was developed and tested in a rat embryonic myocardial cell line (H9c2). In the vigilant vector, a hypoxia response element-incorporated promoter was used as a switch to turn on the gene expression in response to hypoxic signal. Furthermore, a novel double plasmid system was designed to elevate the potency of the vigilant vector. Instead of putting the promoter and the reporter gene in the same plasmid (single plasmid system), we separated them into two plasmids: the transactivator plasmid and reporter plasmid (double plasmid system). The hypoxia response element (HRE)-incorporated promoter increased the expression of a chimeric transcription factor consisting of the yeast GAL4 DNA binding domain and the human nuclear (transcription) factor-B (NF-B) p65 activation domain. The powerful chimeric regulator binds specifically to the upstream activating sequence for GAL4 in the reporter plasmid and activates the transcription of the transgene. Our experiments showed that the HRE-mediated expression could quickly increase 2.08Ϯ0.75-fold within 6 hours of hypoxia and further augmented 7.12Ϯ1.52-fold when the hypoxia condition was prolonged to 24 hours. The hypoxia-inducible double plasmid system dramatically amplified the transgene expression under both hypoxia and normoxia by 412.79Ϯ185.

show abstract

Section: Tang Et Al Hypoxia Inducible Vector For Ischemiamentioning

confidence: 99%

Hypoxia Inducible Double Plasmid System for Myocardial Ischemia Gene Therapy

et al. 2002

View full text Add to dashboard Cite

show abstract

“…effective in blocking the production of angiotensin II by inhibiting ACE in treated mice. Increasing the captopril dose or prolonging captopril treatment resulted in elevated serum ACE levels (37)(38)(39).…”

Section: Captopril Increases Serum Ace Levelsmentioning

confidence: 99%

Captopril Prevents Experimental Autoimmune Myocarditis

Godsel

León

Wang

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

Captopril, an angiotensin-converting enzyme inhibitor, is widely used in the treatment of a variety of cardiomyopathies, but its effect on autoimmune myocarditis has not been addressed experimentally. We investigated the effect of captopril on myosin-induced experimental autoimmune myocarditis. A/J mice, immunized with syngeneic cardiac myosin, were given 75 mg/L of captopril in their drinking water. Captopril dramatically reduced the incidence and severity of myocarditis, which was accompanied by a reduction in heart weight to body weight ratio and heart weight. Captopril specifically interfered with cell-mediated immunity as myosin delayed-type hypersensitivity (DTH) was reduced, while anti-myosin Ab production was not affected. Captopril-treated, OVA-immunized mice also exhibited a decrease in OVA DTH. In myosin-immunized, untreated mice, injection of captopril directly into the test site also suppressed myosin DTH. Interestingly, captopril did not directly affect Ag-specific T cell responsiveness because neither in vivo nor in vitro captopril treatment affected the proliferation, IFN-γ secretion, or IL-2 secretion by Ag-stimulated cultured splenocytes. These results indicate that captopril ameliorates experimental autoimmune myocarditis and may act, at least in part, by interfering with the recruitment of cells to sites of inflammation and the local inflammatory environment.

show abstract

“…In addition, multiple subclinical I͞R incidents can induce cumulative tissue injury leading to chronic degenerative diseases such as vascular dementia, ischemic cardiomyopathy, and renal insufficiency. Cytoprotective strategies using pharmacological agents have yielded limited success in the prevention of I͞R injury (2)(3)(4)(5)(6). Practical difficulties with timing of administration of the therapy, achieving adequate tissue levels of therapeutic product, and unregulated transgene expression pose significant clinical challenges.…”

mentioning

confidence: 99%

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

Pachori

Melo

Hart

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia͞reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia͞reperfusion injury.

show abstract

Protection against ischemia/reperfusion injury and myocardial dysfunction by antisense-oligodeoxynucleotide directed at angiotensin-converting enzyme mRNA

Cited by 17 publications

References 50 publications

Hypoxia Inducible Double Plasmid System for Myocardial Ischemia Gene Therapy

Hypoxia Inducible Double Plasmid System for Myocardial Ischemia Gene Therapy

Captopril Prevents Experimental Autoimmune Myocarditis

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

Contact Info

Product

Resources

About