Linked Life Data

20836698

Source:http://linkedlifedata.com/resource/pubmed/id/20836698

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-3-15
pubmed:abstractText
We examined the hypothesis that vascular and renal dysfunction caused by angiotensin II (Ang II) through increased levels of blood pressure, inflammatory cytokines, and oxidative stress in Sprague-Dawley rats can be prevented by lentiviral-mediated delivery of endothelial heme oxygenase (HO)-1. We targeted the vascular endothelium using a lentiviral construct expressing human HO-1 under the control of the endothelium-specific promoter VE-cadherin (VECAD-HO-1) and examined the effect of long-term human HO-1 expression on blood pressure in Ang II-mediated increases in blood pressure and oxidant stress. A bolus injection of VECAD-HO-1 into the renal artery resulted in expression of human HO-1 for up to 6-9 weeks. Sprague-Dawley rats were implanted with Ang II minipumps and treated with lentivirus carrying either the HO-1 or green fluorescent protein. Renal tissue from VECAD-HO-1-transduced rats expresses human HO-1 mRNA and proteins without an effect on endogenous HO-1. Infusion of Ang II increased blood pressure (p?<?0.001) but decreased vascular relaxation in response to acetylcholine, endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (peNOS) levels, and renal and plasma levels of adiponectin (p?<?0.05); in contrast, plasma tumor necrosis factor-? and monocyte chemoattractant protein-1 levels increased. Ang II-treated animals had higher levels of superoxide anion and inducible nitric oxide synthase and increased urinary protein and plasma creatinine levels. Lentiviral transduction with the VECAD-HO-1 construct attenuated the increase in blood pressure (p?<?0.05), improved vascular relaxation, increased plasma adiponectin, and prevented the elevation in urinary protein and plasma creatinine in Ang II-treated rats. Endothelial-specific expression of HO-1 also reduced oxidative stress and levels of inflammatory cytokines resulting in increased expression of the anti-apoptotic proteins phosphorylated AKT, phosphorylated AMP-activated protein kinase, peNOS, and eNOS. Collectively, these findings demonstrate that endothelial-specific increases in HO-1 expression attenuate Ang II hypertension and the associated vascular dysfunction that is associated with increases in adiponectin and peNOS and reductions in oxidative stress and levels of inflammatory cytokines.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1557-7422
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
271-82
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed-meshheading:20836698-Adiponectin, pubmed-meshheading:20836698-Angiotensin II, pubmed-meshheading:20836698-Animals, pubmed-meshheading:20836698-Animals, Genetically Modified, pubmed-meshheading:20836698-Biological Markers, pubmed-meshheading:20836698-Blood Pressure, pubmed-meshheading:20836698-Disease Models, Animal, pubmed-meshheading:20836698-Endothelium, Vascular, pubmed-meshheading:20836698-Gene Therapy, pubmed-meshheading:20836698-Genetic Vectors, pubmed-meshheading:20836698-HEK293 Cells, pubmed-meshheading:20836698-Heme Oxygenase-1, pubmed-meshheading:20836698-Humans, pubmed-meshheading:20836698-Hypertension, pubmed-meshheading:20836698-Inflammation, pubmed-meshheading:20836698-Kidney, pubmed-meshheading:20836698-Lentivirus, pubmed-meshheading:20836698-Nitric Oxide Synthase, pubmed-meshheading:20836698-Rats, pubmed-meshheading:20836698-Rats, Sprague-Dawley, pubmed-meshheading:20836698-Signal Transduction, pubmed-meshheading:20836698-Superoxides, pubmed-meshheading:20836698-Vasodilation
pubmed:year
2011
pubmed:articleTitle
Lentiviral-human heme oxygenase targeting endothelium improved vascular function in angiotensin II animal model of hypertension.
pubmed:affiliation
Department of Physiology and Pharmacology, The University of Toledo, Toledo, OH 43614, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural