Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats

Hatem E. Sabaawy, Fan Zhang, Xuandai Nguyen, Abdelmonem ElHosseiny, Alberto Nasjletti, Michal Schwartzman, Phyllis Dennery, Attallah Kappas, Nader G. Abraham

    Research output: Contribution to journalArticlepeer-review

    137 Scopus citations

    Abstract

    Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with release of free iron and carbon monoxide. Both heme and carbon monoxide have been implicated in the regulation of vascular tone. A retroviral vector containing human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purification and concentration of the viral particles to achieve 5×109 to 1×1010 colony-forming units per milliliter. The ability of concentrated infectious viral particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac injection of the concentrated infectious viral particles (expressing HHO-1) to 5-day-old spontaneously hypertensive rats resulted in functional expression of the HHO-1 gene and attenuation of the development of hypertension. Rats expressing HHO-1 showed a significant decrease in urinary excretion of a vasoconstrictor arachidonic acid metabolite and a reduction in myogenic responses to increased intraluminal pressure in isolated arterioles. Unexpectedly, HHO-1 chimeric rats showed a simultaneous significant proportionate increase in somatic growth. Thus, delivery of HHO-1 gene by retroviral vector attenuates the development of hypertension and promotes body growth in spontaneously hypertensive rats.

    Original languageEnglish (US)
    Pages (from-to)210-215
    Number of pages6
    JournalHypertension
    Volume38
    Issue number2
    DOIs
    StatePublished - 2001

    All Science Journal Classification (ASJC) codes

    • Internal Medicine

    Keywords

    • Gene transfer
    • Growth
    • Heme oxygenase-1
    • Hypertension
    • Retrovirus

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