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Intramuscular delivery of rAAV-mediated kallikrein gene reduces hypertension and prevents cardiovascular injuries in model rats

引用

Acta Pharmacologica Sinica 2007年第12期28卷 1898-1906页

作者： Yao WANG~(2,3),Ling-bo HOU~(2,3),Zhen-jun LIU~2,Yan WANG~2,Chun-lian CHEN~2,Xiao XIAO~(2,4),Dao-wen WANG~(2,5)~2 Institute of Hypertension and Department of Internal Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science andTechnology,Wuhan 430030,China ~4 Departments of Molecular Genetics and Biochentistry and Gene Therapy Center University of Pittsburgh,Pittsburgh,PA 15261,USA Institute of Hypertension and Department of Internal Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Departments of Molecular Genetics and Biochemistry and Gene Therapy Center Universit

Aim:The overexpression of the human tissue kallikrein （HK） gene can reduceblood pressure and ameliorate the secondary syndromes associated with hyper-tension in animal *** current study was designed to investigate hy-potensive effect of intramuscular delivery of HK ***:We generatedan recombinant adeno-associated virus （rAAV） vector expressing human tissuekallikrein under the control of a cytomegalovirus promoter and administered therAAV-HK vector to a spontaneously hypertensive rat model at a dose of 1×1010virons/rat through intramuscular ***:A persistent,high-level ex-pression of HK post-gene delivery was confirmed by *** systolic bloodpressure in the rats receiving rAAV-LacZ and saline increased from 171.3 mmHg to182.3 mmHg 28 weeks' post *** contrast,the delivery of the HK gene byAAV vectors attenuated the increase of the systolic blood pressure in the *** systolic blood pressure was only slightly lowered （from a level of 174mmHg to 170.5 mmHg） post-vector *** difference in blood pres-sure between the treated group and the control groups is statistically significantat 12.6 *** hypotensive effect of rAAV-HK persisted until the end of thetesting *** addition,a significant amelioration of cardiovascularhypertrophy,renal injury,and collagen depositions in the rAAV-HK-treated ani-mals were also ***:All the effects are comparable with thoseof intravenous ***,the intramuscular administration of rAAV-HKmay be used in gene therapy for hypertension.

关键词： recombinant adeno-associated virus vector human tissue kallikrein intramuscular administration hypertension gene therapy cardiovascular remodeling spontaneously hypertensive rat

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