Prolonged hypotensive effect of human tissue kallikrein gene delivery and recombinant enzyme administration in spontaneous hypertension rats.
- Author:
Huaichang SUN
1
;
Lei ZHANG
;
Anping WANG
;
Zhengfeng XUE
Author Information
1. Jiangsu Provincial Center for Animal Transgenesis and Biopharming, Yangzhou University, Yanhzhou, 225009, P.R. China. sun78564@hotmail.com
- Publication Type:Original Article
- Keywords:
gene delivery;
human tissue kallikrein;
hypotensive effect;
recombinant enzyme administration
- MeSH:
Animals;
Blood Pressure/physiology;
COS Cells;
Cercopithecus aethiops;
Chickens;
Female;
Gene Therapy;
*Gene Transfer Techniques;
Genetic Vectors/genetics/metabolism;
Humans;
Hypertension/genetics/*therapy;
Hypotension/genetics/*metabolism;
Rats;
Rats, Inbred SHR;
Recombinant Proteins/administration & dosage/genetics/metabolism/*therapeutic use;
Tissue Kallikreins/*genetics/metabolism
- From:Experimental & Molecular Medicine
2004;36(1):23-27
- CountryRepublic of Korea
- Language:English
-
Abstract:
To evaluate the feasibility of treating hypertension by human tissue kallikrein gene (KLK1) delivery and by enzyme (rK1) administration, two recombinant vectors expressing KLK1 cDNA were constructed for gene delivery (pcDNA-KLK1) and recombinant enzyme preparation (pOV-KLK1). Expression of the pcDNA-KLK1 vector in COS-1 cells was confirmed by immunofluorescence and in spontaneous hypertension rats (SHR) by enzymatic detection. Following intramuscular or intravenous injection with the pcDNA-KLK1 vector, systolic pressure of SHR was significantly decreased, which lasted for 20 d to two months depending on dose, route and/or time of injection. Egg white containing recombinant hK1 was prepared by injection of egg-laying hens with the oviduct-specific expression vector pOV-KLK1 and administered into SHR via oral gavage. Following administration, systolic pressure of the SHR was decreased to that of normal rats, which lasted for 3-5 d depending on the dosage used. These data suggest that both hKLK1 gene delivery and recombinant enzyme administration can be used as alternative strategies for treating human hypertension.
