Premium
Aldehyde dehydrogenase activator attenuates diabetic cardiomyopathy; a role in improving the quality of resident cardiac stem cells?
Author(s) -
Palaniyandi Suresh Selvaraj,
Disatnik MarieHelene,
Sun Lihan,
Vishnumangalam Jyothi Jayaram,
Xia Xiaoyu,
Pavlovic Aleksandra,
Bhalla Vivek,
Ashley Euan,
MochlyRosen Daria
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.572.3
Subject(s) - aldehyde dehydrogenase , diabetic cardiomyopathy , aldh2 , cardiomyopathy , activator (genetics) , diabetes mellitus , medicine , streptozotocin , in vivo , endocrinology , alcoholic cardiomyopathy , pharmacology , chemistry , biochemistry , enzyme , heart failure , biology , receptor , microbiology and biotechnology
Background Hyperglycemia due to diabetes leads to the production of reactive aldehydes such as 4‐hydroxy‐2‐nonenal (HNE). These toxic aldehydes form adducts on proteins, leading to cell damage and organ dysfunction such as cardiomyopathy. Activation of aldehyde dehydrogenases (ALDHs) which metabolize toxic aldehydes into non‐toxic acids, can ameliorate diabetic cardiomyopathy. Methods Neonatal cardiomyocytes were subjected to high glucose stress (25mM) and treated with Alda‐1 (20 μM), a small molecule ALDH activator that we discovered. Diabetic cardiomyopathy was induced in DBA mice at 8 weeks of age by injecting streptozotocin. The mice with a significant hyperglycemia were treated from 12 week onwards for three months without (n=18) or with (n=24) Alda‐1 (16mg/Kg/day) using Alzet osmotic pumps. Results and Discussion We found that Alda‐1 treatment increased ALDH activity and decreased HNE‐protein adducts formation in vitro and vivo. Alda‐1 reduced adverse cardiac remodeling and myocardial dysfunction. Alda‐1 increased the number of resident cardiac stem cells in the tissue. Human heart samples from patients with cardiomyopathy and diabetes also showed decreased ALDH activity and increased HNE‐protein adducts formation Conclusion Activator of ALDH attenuated diabetic cardiomyopathy in mice. Finally, ALDH activators have potential to be a therapeutic agent to prevent diabetic cardiomyopathy.