title: Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats.
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 5x10(9) to 1x10(10) 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.
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: H E
authors.initials: HE
authors.lastname: Sabaawy
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Nguyen
authors.forename: A
authors.initials: A
authors.lastname: ElHosseiny
authors.forename: A
authors.initials: A
authors.lastname: Nasjletti
authors.forename: M
authors.initials: M
authors.lastname: Schwartzman
authors.forename: P
authors.initials: P
authors.lastname: Dennery
authors.forename: A
authors.initials: A
authors.lastname: Kappas
authors.forename: N G
authors.initials: NG
authors.lastname: Abraham
mesh_terms: D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D001794:Blood Pressure; D002678:Chimera; D046508:Culture Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics* / Q000378:metabolism; D051547:Heme Oxygenase-1; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008565:Membrane Proteins; D011312:Pressure; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D012190:Retroviridae / Q000235:genetics; D014162:Transfection; D014661:Vasoconstriction; D015430:Weight Gain
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1