[Impact of transfection with recombinant adenovirus vector-mediated Klotho gene on myocardial remodeling in a rat model of heart failure].
OBJECTIVE
To assess the impact of transfection with recombinant adenovirus vector-mediated Klotho gene on myocardial remodeling in a rat model of heart failure (HF) by intraperitoneal injection of isoproterenol.


METHODS
Rats were divided into 5 groups by table of exponential random numbers: normal control group, HF group, saline-control HF group, recombinant adenovirus vector transfection group (Ad.EGFP group, 2 × 10¹⁰ pfu, 0.5 ml/rat), pDC316-CMV-EGFP-rKlotho transfection group (Ad.Klotho group, n=5 each). Left ventricular ejection fraction (LVEF) was obtained by echocardiography, hemodynamic parameters obtained by multi-channel physiological recorder, myocardial tissue underwent pathohistological examination. Additionally, the green fluorescin expression was observed on frozen heart section. Myocardial fibrosis correlated gene expression including Klotho gene, collagen I and III was detected by real time-PCR. Moreover, plasma levels of B-type natriuretic peptide (BNP) were measured with ELISA.


RESULTS
Compared to saline control HF group, LVEF, LVSP and ±dp/dtmax were significantly increased, myocardial fibrosis and myocardial remodeling were significantly attenuated in the Ad. Klotho group and there was green fluorescin distribution in myocardial tissues of Ad. Klotho group. Klotho expression was down-regulated and collagen I and III expression was upregulated in HF rats compared to normal control group (all P<0.05) and these changes could be significantly reversed in Ad. Klotho group (all P<0.05). Plasma BNP level was also significantly lower in Ad. Klotho group than in HF group (P<0.05).


CONCLUSIONS
Klotho gene transfection could improve cardiac function and attenuate cardiac remodeling and reducing myocardial fibrosis.
Graduate College of Guilin Medical University, Guilin 541004, China.
Zheng
Z
Jia
Email: weiling43@163.com.
Ling
L
Wei
Qian
Q
Liu
Ziying
Z
Zhu
Jing
J
Yang
Xiaohua
X
Yang
Shibao
S
Gan
Weiqiang
W
Chen
Liping
L
Zhang
D000256:Adenoviridae; D000818:Animals; D004195:Disease Models, Animal; D004452:Echocardiography; D015870:Gene Expression; D005822:Genetic Vectors; D005966:Glucuronidase; D006333:Heart Failure; D006439:Hemodynamics; D007545:Isoproterenol; D000090265:Klotho Proteins; D009206:Myocardium; D020097:Natriuretic Peptide, Brain; D051381:Rats; D014162:Transfection; D016277:Ventricular Function, Left
D020097:Natriuretic Peptide, Brain; D005966:Glucuronidase; D000090265:Klotho Proteins; D007545:Isoproterenol