Down-regulation of the human ether-a-go-go-related gene in rat cardiac hypertrophy.
BACKGROUND
Cardiac hypertrophy is a risk factor for QT prolongation and cardiac sudden death. In this study, the authors examined the expressional regulation on the rat human ether-a-go-go-related gene (HERG), which encodes a structural subunit of the rapid component of the delayed rectifier potassium current (I(Kr)), during myocardial hypertrophy using rat as a model system.


METHODS
Cardiac hypertrophy was established in Sprague-Dawley rats by coarctation of the abdominal aorta [left ventricular hypertrophy (LVH) group]. Sham-operated rats were defined as control group (Ctrl group). Hemodynamic, morphologic and histologic parameters were recorded 6 weeks after operation. In addition, the expression of HERG was also determined using a combination of real-time polymerase chain reaction, Western blot and immunohistochemical analyses.


RESULTS
Compared with the sham-operated Ctrl group, abdominal aortic coarctation induced LVH in the LVH group, as evidenced by significantly increased ratios of heart weight/left ventricular weight to body weight and enlarged left ventricular myocytes in the histologic sections. The hemodynamic profile revealed significant increases in heart rate and left ventricular end-diastolic pressure, as well as a decrease in the maximal rate of left ventricular pressure fall in the LVH rats, when compared with the Ctrl rats. Electrocardiograms showed prolonged QT and corrected QT intervals. On the molecular level, a significant reduction of HERG, messengerRNA and protein was observed in LVH group, which was inversely correlated with prolonged corrected QT (r = -0.842, P = 0.000).


CONCLUSIONS
The expressional down-regulation of HERG gene may constitute a novel mechanism for QT prolongation during cardiac hypertrophy.
Department of Cardiology, The First Affiliated Hospital, Shantou University Medical College, China.
Chuangjia
C
Hu
Chunying
C
Yan
Jijin
J
Lin
Shukai
S
Liu
Yanyan
Y
Li
D000818:Animals; D001012:Aorta, Abdominal; D001017:Aortic Coarctation / Q000150:complications; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008133:Long QT Syndrome / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D017931:DNA Primers; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D012333:RNA, Messenger