Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenomedullin (AM) is a potent vasodilator expressed in tissues relevant to cardiac and renal functions. Our previous study showed that delivery of the human AM gene in the form of naked DNA caused a prolonged reduction of blood pressure in genetically hypertensive rats. In this study, we evaluated potential protective effects of adenovirus-mediated AM gene delivery on salt-induced cardiorenal lesions in hypertensive Dahl saltsensitive (DSS) rats. Adenovirus carrying the human AM cDNA under the control of the cytomegalovirus promoter-enhancer (Ad.CMV-hAM) was generated by homologous recombination of E. coli. Expression of recombinant human AM was detected by a radioimmunoassay in the medium of human embryonic kidney 293 cells transfected with Ad.CMV-hAM. A single intravenous injection of Ad.CMV-hAM caused a significant reduction of systolic blood pressure for 4 weeks in DSS rats compared with control rats with or without injection of adenovirus carrying the green fluorescent protein gene. AM gene delivery significantly reduced left ventricular mass and urinary protein, increased cAMP levels, and enhanced renal function as evidenced by increases in glomerular filtration rate and renal blood flow. Morphological investigations showed that AM gene transfer reduced cardiomyocyte diameter and interstitial fibrosis in the heart as well as glomerular sclerosis, tubular disruption, and protein cast accumulation in the kidney. Expression of human AM mRNA was identified in rat heart, kidney, lung, liver, and aorta, and immunoreactive human AM levels were measured in rat plasma and urine. These results indicate that human AM gene delivery protects against salt-induced hypertension and cardiac and renal lesions in DSS rats via activation of cAMP as a second messenger. These findings provide new insights into the role of AM in salt-induced hypertension and may have implications in therapeutic applications to salt-related cardiovascular and renal diseases.
 ...
PMID:Human adrenomedullin gene delivery protects against cardiac hypertrophy, fibrosis, and renal damage in hypertensive dahl salt-sensitive rats. 1098 55

Adrenomedullin (AM) is a potent vasodilator and natriuretic peptide that plays an important role in cardiorenal function. In this study, we explored the potential protective role of AM in volume-dependent hypertension by somatic gene delivery. Adenovirus containing the human AM cDNA under the control of the cytomegalovirus promoter/enhancer was administered into deoxycorticosterone acetate (DOCA)-salt hypertensive rats via tail vein injection. A single injection of the human AM gene resulted in a prolonged reduction of blood pressure with a maximal reduction of 41 mm Hg 9 days after gene delivery. Human AM gene delivery enhanced renal function, as indicated by a 3-fold increase in renal blood flow and a 2-fold increase in glomerular filtration rate (n=5, P<0.05). Histological examination of the kidney revealed a significant reduction in glomerular sclerosis, tubular injury, luminol protein cast accumulation, and interstitial fibrosis as well as urinary protein. Human AM gene delivery caused significant decreases in left ventricular weight and cardiomyocyte diameter, which were accompanied by reduced interstitial fibrosis and extracellular matrix formation within the heart. Expression of human AM mRNA was detected in the kidney, adrenal gland, heart, aorta, lung, and liver; immunoreactive human AM levels were measured in urine and plasma. Significant increases in urinary and cardiac cAMP levels were observed in DOCA-salt rats receiving the human AM gene, indicating activation of the AM receptor. These findings showed that AM gene delivery attenuates hypertension, protects against cardiac remodeling and renal damage in volume-overload hypertension, and may have significance in therapeutic applications in cardiovascular and renal diseases.
 ...
PMID:Adrenomedullin gene delivery attenuates hypertension, cardiac remodeling, and renal injury in deoxycorticosterone acetate-salt hypertensive rats. 1111 14

Adrenomedullin (AM) is a potent vasodilator expressed in tissues relevant to cardiovascular function. AM peptide has been shown to inhibit the proliferation and migration of vascular smooth muscle cells in vitro. However, the effect of AM on blood vessels after vascular injury in vivo has not been elucidated. In order to explore the potential roles of AM in vascular biology, we evaluated the effect of AM by local gene delivery on neointima formation in balloon-injured rat artery. Adenovirus carrying the human AM cDNA under the control of cytomegalovirus promoter/enhancer (Ad.CMV-hAM) was generated by homologous recombination. After delivery of Ad.CMV-hAM into rat left carotid artery, we identified the expression of human AM mRNA in the left carotid artery, but not in the right carotid artery, heart or kidney by reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Following local AM gene delivery, we observed a 51% reduction in intima/media ratio at the injured site as compared with that of control rats injected with the luciferase gene (n=7, P<0.01). AM gene transfer resulted in regeneration of endothelium as compared to the control. AM gene delivery significantly increased cGMP levels in balloon-injured arteries. These results indicate that AM contributes to reduction of neointima formation by promotion of re-endothelialization and inhibition of vascular smooth muscle cell proliferation via cGMP-dependent signaling pathway.
 ...
PMID:Adrenomedullin gene delivery inhibits neointima formation in rat artery after balloon angioplasty. 1266 32