Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-5-20
pubmed:abstractText
Our studies have established that a single intracardiac administration of the retroviral vector containing angiotensin II type I receptor antisense gene causes prolonged antihypertensive actions in the spontaneously hypertensive rat. These results suggest that antisense gene therapy is a conceptually valid strategy for the control of hypertension at the genetic level. To evaluate whether attenuation of the pathophysiological aspects of hypertension are dependent on the blood pressure lowering actions of antisense gene therapy, we chose the renin transgenic rat as a hypertensive animal model and cardiac hypertrophy as the hypertension-associated pathophysiology. A single intracardiac administration of the retroviral vector containing angiotensin II type I receptor antisense in the neonatal rat resulted in long-term expression of the antisense transgene in various cardiovascular-relevant tissues, including the heart. This expression was associated with a significant attenuation of cardiac hypertrophy despite its failure to normalize high blood pressure. Developmental studies indicated that cardiac hypertrophy was evident as early as 16 days of age in viral vector-treated control transgenic rats, despite these animals exhibiting normal blood pressure. These observations demonstrate that, in the renin-transgenic rat, the onset of cardiac hypertrophy occurs during development and is prevented without normalization of high blood pressure. Collectively, these results provide further proof of the concept and indicate that antisense gene therapy could successfully target the local tissues' renin-angiotensin system to produce beneficial cardiovascular outcomes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
969-75
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12019278-Actins, pubmed-meshheading:12019278-Animals, pubmed-meshheading:12019278-Animals, Genetically Modified, pubmed-meshheading:12019278-Atrial Natriuretic Factor, pubmed-meshheading:12019278-Blood Pressure, pubmed-meshheading:12019278-Cardiomegaly, pubmed-meshheading:12019278-DNA, Antisense, pubmed-meshheading:12019278-Female, pubmed-meshheading:12019278-Gene Expression, pubmed-meshheading:12019278-Gene Therapy, pubmed-meshheading:12019278-Genetic Vectors, pubmed-meshheading:12019278-Male, pubmed-meshheading:12019278-RNA, Messenger, pubmed-meshheading:12019278-Rats, pubmed-meshheading:12019278-Rats, Sprague-Dawley, pubmed-meshheading:12019278-Receptor, Angiotensin, Type 1, pubmed-meshheading:12019278-Receptors, Angiotensin, pubmed-meshheading:12019278-Renin, pubmed-meshheading:12019278-Retroviridae, pubmed-meshheading:12019278-Treatment Outcome
pubmed:year
2002
pubmed:articleTitle
Blood pressure-independent attenuation of cardiac hypertrophy by AT(1)R-AS gene therapy.
pubmed:affiliation
Hypertension Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.