Key result
Empagliflozin reduces glucose-induced cardiomyocyte apoptosis and oxidative stress by activating AMPK/PGC-1α and suppressing RhoA/ROCK.
Why the study?
Empagliflozin reduces HF hospitalization in diabetic patients, but the molecular mechanisms underlying its cardioprotection in diabetic cardiomyopathy remain unclear.
Does empagliflozin reduce oxidative stress and apoptosis in cardiomyocytes exposed to high glucose?
Does empagliflozin reduce oxidative stress and apoptosis in cardiomyocytes exposed to high glucose?
Empagliflozin exerts cardioprotective effects against high glucose-induced injury via AMPK/PGC-1α activation and RhoA/ROCK pathway suppression, independent of SGLT2.
Hypothesis-generating for AMPK-dependent cardioprotection by empagliflozin in hyperglycemia; leaves clinical translation to diabetic cardiomyopathy open.
BACKGROUND: Diabetic cardiomyopathy (DCM) increases the risk of hospitalization for heart failure (HF) and mortality in patients with diabetes mellitus. However, no specific therapy to delay the progression of DCM has been identified. Mitochondrial dysfunction, oxidative stress, inflammation, and calcium handling imbalance play a crucial role in the pathological processes of DCM, ultimately leading to cardiomyocyte apoptosis and cardiac dysfunctions. Empagliflozin, a novel glucose-lowering agent, has been confirmed to reduce the risk of hospitalization for HF in diabetic patients. Nevertheless, the molecular mechanisms by which this agent provides cardioprotection remain unclear. AIM: To investigate the effects of empagliflozin on high glucose (HG)-induced oxidative stress and cardiomyocyte apoptosis and the underlying molecular mechanism. METHODS: mRNA expression. Western blot analysis was used to measure the phosphorylation of AMP-activated protein kinase (AMPK) and myosin phosphatase target subunit 1 (MYPT1), as well as the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and active caspase-3 protein levels. RESULTS: experiment, the findings indicate that treatment of cardiomyocytes with empagliflozin (10 μM) or fasudil (FA) (a ROCK inhibitor, 100 μM) or overexpression of PGC-1α significantly attenuated HG-induced mitochondrial injury, oxidative stress, and cardiomyocyte apoptosis. However, the above effects were partly reversed by the addition of compound C (CC). In cells exposed to HG, empagliflozin treatment increased the protein levels of p-AMPK and PGC-1α protein while decreasing phosphorylated MYPT1 levels, and these changes were mitigated by the addition of CC. Adding FA and overexpressing PGC-1α in cells exposed to HG substantially increased PGC-1α protein levels. In addition, no sodium-glucose cotransporter (SGLT)2 protein expression was detected in cardiomyocytes. CONCLUSION: Empagliflozin partially achieves anti-oxidative stress and anti-apoptotic effects on cardiomyocytes under HG conditions by activating AMPK/PGC-1α and suppressing of the RhoA/ROCK pathway independent of SGLT2.
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Li et al. (2023) studied Diabetic cardiomyopathy. Empagliflozin vs. High glucose alone was evaluated on High glucose-induced mitochondrial injury, oxidative stress, and cardiomyocyte apoptosis. Empagliflozin attenuated high glucose-induced mitochondrial injury, oxidative stress, and cardiomyocyte apoptosis by activating AMPK/PGC-1α and suppressing the RhoA/ROCK pathway.
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