PMID- 12425814
OWN - NLM
STAT- MEDLINE
DCOM- 20030113
LR  - 20121115
IS  - 0376-2491 (Print)
IS  - 0376-2491 (Linking)
VI  - 82
IP  - 16
DP  - 2002 Aug 25
TI  - [Hypotensive effect of encapsulated genetically engineered fibroblasts expressing 
      mutant atrial natriuretic peptide in hypertensive rats].
PG  - 1086-9
AB  - OBJECTIVE: To study the inhibitive effect of subcutaneous implantation of capsule 
      filled with fibroblasts engineered to secrete the mutant human atrial natriuretic 
      peptide (mhANP) on blood pressure in young spontaneously hypertensive rats (SHR) 
      and to explore the feasibility of gene therapy for the treatment of hypertension. 
      METHODS: A recombinant retroviral vector pLHY24 bearing mhANP cDNA was 
      constructed. Primary fibroblasts derived from the skin of new born SHR were 
      cultured and transfected with the vector pLHY24 to establish a genetically 
      modified fibroblast line or transfected with the blank vector pLNCX. Then the two 
      kinds of cell culture were put into specially made capsules with microholes. The 
      capsules filled with the genetically modified allogenic fibroblasts and those 
      with blank vector were implanted into the dorsal subcutaneous tissues of two 
      groups of 10 young SHR respectively. The plasma ANP, blood pressure, urine 
      volume, potassium and sodium concentrations in urine, and body weight were 
      determined every week for 7 weeks. RESULTS: After delivery of retroviral vector 
      bearing mhANP gene into the packaging cell PA317 and the primary fibroblasts, 
      immunoreactive mhANP were detected in the cell culture medium at the 
      concentration of (5.84 +/- 0.07) and (13.37 +/- 2.36) ng.10(-6) cells.24 h(-1) 
      respectively. One week after implantation of the genetically modified allogenic 
      fibroblasts the plasma level of mhANP was 131 pg/ml +/- 8 pg/ml, significantly 
      higher than that in control group (104 pg/ml +/- 7 pg/ml, t = 8.62, P < 0.001). 
      Although the blood pressure increased along with aging after the gene transfer, 
      an obvious delay of blood pressure increase was seen significantly lower in test 
      group [from (129 +/- 9) to (169 +/- 9) mm Hg] than that in the control group 
      [from (145 +/- 10) to (181 +/- 9) mm Hg, P < 0.05 or 0.01]. A maximal blood 
      pressure reduction of 28 mm Hg in young SHR was observed 7 days after 
      transplantation as compared with controls. In addition, there was an obvious 
      increase in urine volume of test group 2 weeks after transplantation and the 
      effect lasted for more than 2 weeks. However, there were no statistical 
      differences in body weight and the concentrations of K(+) and Na(+) in urine. 
      CONCLUSION: Subcutaneous implantation of the encapsulated genetically modified 
      fibroblasts engineered to secrete mutant ANP causes a lowering effect of blood 
      pressure in young SHR.
FAU - Li, Tao
AU  - Li T
AD  - National Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, 
      Beijing 100005, China.
FAU - Liang, Hongyan
AU  - Liang H
FAU - Lu, Guo
AU  - Lu G
FAU - Shi, Ruiwen
AU  - Shi R
FAU - Lu, Shengdong
AU  - Lu S
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Zhonghua Yi Xue Za Zhi
JT  - Zhonghua yi xue za zhi
JID - 7511141
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Capsules)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
SB  - IM
MH  - Animals
MH  - Antihypertensive Agents/*metabolism
MH  - Atrial Natriuretic Factor/*genetics/physiology
MH  - Blood Pressure/physiology
MH  - Capsules
MH  - Fibroblasts/cytology/*metabolism
MH  - Gene Expression
MH  - Genetic Therapy/methods
MH  - Humans
MH  - Hypertension/genetics/physiopathology/*therapy
MH  - Male
MH  - Mutation
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Time Factors
MH  - Transfection
EDAT- 2002/11/12 04:00
MHDA- 2003/01/14 04:00
CRDT- 2002/11/12 04:00
PHST- 2002/11/12 04:00 [pubmed]
PHST- 2003/01/14 04:00 [medline]
PHST- 2002/11/12 04:00 [entrez]
PST - ppublish
SO  - Zhonghua Yi Xue Za Zhi. 2002 Aug 25;82(16):1086-9.