AIMS: About 40% of East Asians carry an aldehyde dehydrogenase-2*2 (ALDH2*2) allele, and the influence of the ALDH2*2 allele on human cardioprotection has not been studied. This study was designed to evaluate the effect of ALDH2*2 allele on cardioprotection of patients with congenital heart diseases after open-heart surgery. METHODS AND RESULTS: The right atrial appendage was harvested before performing cardiopulmonary bypass in cyanotic and acyanotic congenital heart disease groups (n = 20 per group). Tissues were assayed to determine the impact of cyanosis on metabolic remodelling. A prospective cohort of Tetralogy of Fallot (TOF) patients (n = 118) was recruited to investigate the influence of the ALDH2*2 allele on cardioprotection after surgical repair. Myocardium samples were dissected after cardioplegia. ALDH2 activity, oxidative stress and glutathione (GSH) levels, and activating transcription factor-4 (ATF4) were analysed. After genotyping and grouping, all of the experimental and clinical results were compared between ALDH2*2 carriers and non-carriers. Cyanosis inhibited ALDH2 activity and led to aldehyde accumulation in ALDH2*2 carriers. This accumulation in turn increased expression of ATF4 and resulted in larger myocardium GSH pools. The differences in ALDH2 activity and GSH level between carriers and non-carriers disappeared during cardioplegic arrest, and more aldehydes accumulated in the non-carriers. Consequently, ALDH2*2 carriers showed lower postoperative troponin I, inotrope score, and shorter postoperative length of ICU and hospital stay. CONCLUSIONS: ALDH2*2 carriers with cyanotic congenital heart disease were associated with an induced metabolic remodelling phenotype and a compensatory myocardium GSH pool. When ALDH2 activity was impaired during open-heart surgery, this larger GSH pool could lead to unexpectedly better cardioprotection. This may aid in the prediction of cardioprotection outcomes and identification of individualized cardioprotective strategies.
AIMS: About 40% of East Asians carry an aldehyde dehydrogenase-2*2 (ALDH2*2) allele, and the influence of the ALDH2*2 allele on human cardioprotection has not been studied. This study was designed to evaluate the effect of ALDH2*2 allele on cardioprotection of patients with congenital heart diseases after open-heart surgery. METHODS AND RESULTS: The right atrial appendage was harvested before performing cardiopulmonary bypass in cyanotic and acyanotic congenital heart disease groups (n = 20 per group). Tissues were assayed to determine the impact of cyanosis on metabolic remodelling. A prospective cohort of Tetralogy of Fallot (TOF) patients (n = 118) was recruited to investigate the influence of the ALDH2*2 allele on cardioprotection after surgical repair. Myocardium samples were dissected after cardioplegia. ALDH2 activity, oxidative stress and glutathione (GSH) levels, and activating transcription factor-4 (ATF4) were analysed. After genotyping and grouping, all of the experimental and clinical results were compared between ALDH2*2 carriers and non-carriers. Cyanosis inhibited ALDH2 activity and led to aldehyde accumulation in ALDH2*2 carriers. This accumulation in turn increased expression of ATF4 and resulted in larger myocardium GSH pools. The differences in ALDH2 activity and GSH level between carriers and non-carriers disappeared during cardioplegic arrest, and more aldehydes accumulated in the non-carriers. Consequently, ALDH2*2 carriers showed lower postoperative troponin I, inotrope score, and shorter postoperative length of ICU and hospital stay. CONCLUSIONS:ALDH2*2 carriers with cyanotic congenital heart disease were associated with an induced metabolic remodelling phenotype and a compensatory myocardium GSH pool. When ALDH2 activity was impaired during open-heart surgery, this larger GSH pool could lead to unexpectedly better cardioprotection. This may aid in the prediction of cardioprotection outcomes and identification of individualized cardioprotective strategies.
Authors: Antje D Ebert; Kazuki Kodo; Ping Liang; Haodi Wu; Bruno C Huber; Johannes Riegler; Jared Churko; Jaecheol Lee; Patricia de Almeida; Feng Lan; Sebastian Diecke; Paul W Burridge; Joseph D Gold; Daria Mochly-Rosen; Joseph C Wu Journal: Sci Transl Med Date: 2014-09-24 Impact factor: 17.956
Authors: Eric R Gross; Vanessa O Zambelli; Bryce A Small; Julio C B Ferreira; Che-Hong Chen; Daria Mochly-Rosen Journal: Annu Rev Pharmacol Toxicol Date: 2014-09-29 Impact factor: 13.820
Authors: Katia M S Gomes; Juliane C Campos; Luiz R G Bechara; Bruno Queliconi; Vanessa M Lima; Marie-Helene Disatnik; Paulo Magno; Che-Hong Chen; Patricia C Brum; Alicia J Kowaltowski; Daria Mochly-Rosen; Julio C B Ferreira Journal: Cardiovasc Res Date: 2014-05-09 Impact factor: 10.787
Authors: Alain van Mil; Geerthe Margriet Balk; Klaus Neef; Jan Willem Buikema; Folkert W Asselbergs; Sean M Wu; Pieter A Doevendans; Joost P G Sluijter Journal: Cardiovasc Res Date: 2018-12-01 Impact factor: 10.787
Authors: Akiko Matsumoto; David C Thompson; Ying Chen; Kyoko Kitagawa; Vasilis Vasiliou Journal: Environ Health Prev Med Date: 2016-10-06 Impact factor: 3.674