Down-regulation of endothelin-1 and alteration of apoptosis signaling following left ventricular volume reduction surgery in heart failure of adult rats.
While left ventricular (LV) reduction surgery (LVR) is a novel treatment for severe heart failure, alteration of signal transduction pathways by this surgery is unknown. LV endothelin-1 plays a critical role in LV remodeling following myocardial infarction (MI). Another possible mechanism of remodeling is myocardial cell loss due to apoptosis. The purpose of the present study was to determine whether the LV endothelin-1 level and apoptosis signaling change after LVR. Adult rats were divided into two groups: non-MI group and MI group, and the MI group was subjected to permanent ligation of the left anterior descending artery. Four weeks later, rats in the MI group were subjected to LVR (LVR group) or a sham operation (OMI group). Two weeks after the second operation, echocardiography revealed that LVR improved LV systolic function and remodeling. Upregulation of LV endothein-1 was detected only in the OMI group but not in the non-MI group nor in the LVR group. The percentage of terminal deoxynucleotidyl transfer-mediated end-labeling of fragmented nuclei (TUNEL)-positive cardiac myocytes was significantly higher in the OMI group than in the LVR group or the non-MI group. Western blotting of extracts from the left ventricle showed that bcl-2 and bcl-xL levels were restored and caspase-3 activation was repressed after LVR. Thus, LVR modulates the expression of endothelin-1 and apoptosis signaling in failing hearts. These alterations of signal transduction pathways might contribute to the beneficial effects of LVR on systolic function in heart failure.
Kawamura
Teruhisa
T
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Hasegawa
Koji
K
Morimoto
Tatsuya
T
Iwakura
Atsushi
A
Nishina
Takeshi
T
Nomoto
Takuya
T
Komeda
Masashi
M
D000818:Animals; D017209:Apoptosis; D006348:Cardiac Surgical Procedures; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D004452:Echocardiography; D019332:Endothelin-1 / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D020287:In Situ Nick-End Labeling; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling; D051020:bcl-X Protein / Q000378:metabolism
C494813:Bcl2l1 protein, rat; D019332:Endothelin-1; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C505410:Casp3 protein, rat; D053148:Caspase 3