Alpha-lipoic acid protects against pressure overload-induced heart failure via ALDH2-dependent Nrf1-FUNDC1 signaling.
Wenjia LiLei YinXiaolei SunJian WuZhen DongKai HuAijun SunJunbo GePublished in: Cell death & disease (2020)
Alpha-lipoic acid (α-LA), a well-known antioxidant, was proved to active ALDH2 in nitrate tolerance and diabetic animal model. However, the therapeutic advantage of α-LA for heart failure and related signaling pathway have not been explored. This study was designed to examine the role of α-LA-ALDH2 in heart failure injury and mitochondrial damage. ALDH2 knockout (ALDH2-/-) mice and primary neonatal rat cardiomyocytes (NRCMs) were subjected to assessment of myocardial function and mitochondrial autophagy. Our data demonstrated α-LA significantly reduced the degree of TAC-induced LV hypertrophy and dysfunction in wild-type mice, not in ALDH2-/- mice. In molecular level, α-LA significantly restored ALDH2 activity and expression as well as increased the expression of a novel mitophagy receptor protein FUNDC1 in wild-type TAC mice. Besides, we confirmed that ALDH2 which was activated by α-LA governed the activation of Nrf1-FUNDC1 cascade. Our data suggest that α-LA played a positive role in protecting the heart against adverse effects of chronic pressure overload.
Keyphrases
- wild type
- oxidative stress
- heart failure
- diabetic rats
- signaling pathway
- left ventricular
- poor prognosis
- high fat diet induced
- high glucose
- induced apoptosis
- binding protein
- nitric oxide
- type diabetes
- drug induced
- cardiac resynchronization therapy
- endoplasmic reticulum stress
- electronic health record
- atrial fibrillation
- cell death
- metabolic syndrome
- big data
- pi k akt
- insulin resistance
- nlrp inflammasome
- small molecule
- long non coding rna
- protein protein
- adverse drug
- single molecule