Dysregulation of cardiac mitochondrial aldehyde dehydrogenase 2: Studies in dogs with chronic heart failure

• Published in: Journal of Molecular and Cellular Cardiology Plus (Online) 2024-06, Vol.8, p.100067, Article 100067
• Main Authors: Gupta, Ramesh C., Singh-Gupta, Vinita, Szekely, Kristina J., Zhang, Kefei, Lanfear, David E., Sabbah, Hani N.
• Format: Article
• Language: English
• Subjects: Aldehyde dehydrogenase; Heart failure, aldehydes; Mitochondria; Protein kinase
• ISSN: 2772-9761; 2772-9761
• DOI: 10.1016/j.jmccpl.2024.100067

Mitochondrial (MITO) dysfunction occurs in the failing heart and contributes to worsening of heart failure (HF). Reduced aldehyde dehydrogenase 2 (ALDH2) in left ventricular (LV) myocardium of diabetic hearts has been implicated in MITO dysfunction through accumulation of toxic aldehydes including and elevated levels of 4-hydroxy-2-nonenal (4HNE). This study examined whether dysregulation of MITO ALDH2 (mALDH2) occurs in mitochondria of the failing LV and is associated with increased levels of 4HNE. LV tissue from 7 HF and 7 normal (NL) dogs was obtained. Protein quantification of total mitochondrial ALDH2 (t-mALDH2), phosphorylated mALDH2 (p-mALDH2), total MITO protein kinase c epsilon (t-mPKCε), phosphorylated mPKCε (p-mPKCε) was performed by Western blotting, and total mALDH2 enzymatic activity was measured. Protein adducts of 4HNE-MITO and 4HNE-mALDH2 were also measured in MITO fraction by Western Blotting. Protein level of t-mALDH2 was decreased in HF compared with NL dogs (0.63 ± 0.07 vs 1.17 ± 0.08, p