ArticlePloS one2016
Cardiac Mitochondrial Respiratory Dysfunction and Tissue Damage in Chronic Hyperglycemia Correlate with Reduced Aldehyde Dehydrogenase-2 Activity.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Is Type 2 Diabetes a Modifiable Risk Factor for the Evolution and Progression of Heart Failure With a Preserved Ejection Fraction?Journal of the American College of Cardiology · 2025Review
- Irisin deficiency exacerbates cardiac dysfunction and enhances hemorrhage injury in hemorrhage/resuscitation.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- Targeted Overexpression of Mitochondrial ALDH2 in Coronary Endothelial Cells Mitigates HFpEF in a Diabetic Mouse Model.Biomolecules · 2025Article
- The antioxidant l-Ergothioneine prevents cystine lithiasis in the Slc7a9Redox biology · 2023Article
- Effects of intracardiac delivery of aldehyde dehydrogenase 2 gene in myocardial salvage.Gene therapy · 2023Article
- Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence?Heart failure reviews · 2022Review
- Aldehyde Dehydrogenase 2 Activator Augments the Beneficial Effects of Empagliflozin in Mice with Diabetes-Associated HFpEF.International journal of molecular sciences · 2022Article
- Article
- Diabetic Aldehyde Dehydrogenase 2 Mutant (ALDH2*2) Mice Are More Susceptible to Cardiac Ischemic-Reperfusion Injury Due to 4-Hydroxy-2-Nonenal Induced Coronary Endothelial Cell Damage.Journal of the American Heart Association · 2021Article
- The role of mitochondria in metabolic disease: a special emphasis on heart dysfunction.The Journal of physiology · 2021Review
- 4-Hydroxy-2-nonenal, a lipid peroxidation product, as a biomarker in diabetes and its complications: challenges and opportunities.Free radical research · 2021Review
- Mitochondrial Transplantation Modulates Inflammation and Apoptosis, Alleviating Tendinopathy Both In Vivo and In Vitro.Antioxidants (Basel, Switzerland) · 2021Article
- A Novel ALDH2 Activator AD-9308 Improves Diastolic and Systolic Myocardial Functions in Streptozotocin-Induced Diabetic Mice.Antioxidants (Basel, Switzerland) · 2021Article
- The effect of ALDH2 rs671 gene mutation on clustering of cardiovascular risk factors in a big data study of Chinese population: associations differ between the sexes.BMC cardiovascular disorders · 2020Observational
- 4-Hydroxy-2-nonenal attenuates 8-oxoguanine DNA glycosylase 1 activity.Journal of cellular biochemistry · 2020Article
- Article
- Cardiac Function is not Susceptible to Moderate Disassembly of Mitochondrial Respiratory Supercomplexes.International journal of molecular sciences · 2020Article
- ALDH1A3 Regulations of Matricellular Proteins Promote Vascular Smooth Muscle Cell Proliferation.iScience · 2019Article
- Effects of nuclear respiratory factor‑1 on apoptosis and mitochondrial dysfunction induced by cobalt chloride in H9C2 cells.Molecular medicine reports · 2019Article
- Modelling cardiac fibrosis using three-dimensional cardiac microtissues derived from human embryonic stem cells.Journal of biological engineering · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial isozyme of the heart involved in the metabolism of toxic aldehydes produced from oxidative stress. We hypothesized that hyperglycemia-mediated decrease in ALDH2 activity may impair mitochondrial respiration and ultimately result in cardiac damage. A single dose (65 mg/kg; i.p.) streptozotocin injection to rats resulted in hyperglycemia with blood glucose levels of 443 ± 9 mg/dl versus 121 ± 7 mg/dl in control animals, p<0.0001, N = 7-11. After 6 months of diabetes mellitus (DM) induction, the rats were sacrificed after recording the functionality of their hearts. Increase in the cardiomyocyte cross sectional area (446 ± 32 μm2 Vs 221 ± 10 μm2; p<0.0001) indicated cardiac hypertrophy in DM rats. Both diastolic and systolic dysfunctions were observed with DM rats compared to controls. Most importantly, myocardial ALDH2 activity and levels were reduced, and immunostaining for 4HNE protein adducts was increased in DM hearts compared to controls. The mitochondrial oxygen consumption rate (OCR), an index of mitochondrial respiration, was decreased in mitochondria isolated from DM hearts compared to controls (p<0.0001). Furthermore, the rate of mitochondrial respiration and the increase in carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)-induced maximal respiration were also decreased with chronic hyperglycemia. Chronic hyperglycemia reduced mitochondrial OXPHOS proteins. Reduced ALDH2 activity was correlated with mitochondrial dysfunction, pathological remodeling and cardiac dysfunction, respectively. Our results suggest that chronic hyperglycemia reduces ALDH2 activity, leading to mitochondrial respiratory dysfunction and consequently cardiac damage and dysfunction.
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