Regulation of the CB1R/AMPK/PGC-1α signaling pathway in mitochondria of mouse hearts and cardiomyocytes with chronic intermittent hypoxia

Hu, Zixuan; Mu, Sufang; Zhao, Li; Dou, Zhanjun; Wang, Peipei; Zhang, Junfeng; Jin, Ning; Lu, Xin; Xu, Xia; Liang, Tao; Duan, Yuting; Xiong, Yong; Wang, Bei

doi:10.1007/s11325-023-02863-8

Cited by 2 publications

(4 citation statements)

References 70 publications

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“…Previous studies have shown that under IH conditions, H9C2 cardiomyocytes are also damaged, ROS is markedly increased, oxidative stress in cardiomyocytes is increased, mitochondria are seriously fragmented, the membrane potential is decreased, and the mitochondrial function is impaired. Together, these data show that CIH has serious damaging effects on db/db mice and H9C2 cardiomyocytes [40][41][42].…”

Section: Plos Onementioning

confidence: 63%

Chronic intermittent hypoxia aggravated diabetic cardiomyopathy through LKB1/AMPK/Nrf2 signaling pathway

Liu,

Si,

et al. 2024

PLoS ONE

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Chronic intermittent hypoxia (CIH) may play an important role in the development of diabetic cardiomyopathy (DCM). However, the exact mechanism of CIH-induced myocardial injury in DCM remains unclear. In vivo, the db/db mice exposed to CIH were established, and in vitro, the H9C2 cells were exposed to high glucose (HG) combined with intermittent hypoxia (IH). The body weight (BW), fasting blood glucose (FBG) and food intake were measured every two weeks. The glycolipid metabolism was assessed with the oral glucose tolerance test (OGTT) and insulin resistance (IR). Cardiac function was detected by echocardiography. Cardiac pathology was detected by HE staining, Masson staining, and transmission electron microscopy. The level of reactive oxygen species (ROS) in myocardial tissue was detected by dihydroethidium (DHE). The apoptosis was detected by TUNEL staining. The cell viability, ROS, and the mitochondrial membrane potential were detected by the cell counting kit-8 (CCK-8) assay and related kits. Western blotting was used to analyze the liver kinase B1/AMP-activated protein kinase/ nuclear factor-erythroid 2-related factor 2 (LKB1/AMPK/Nrf2) signaling pathway. CIH exposure accelerated glycolipid metabolism disorders and cardiac injury, and increased the level of cardiac oxidative stress and the number of positive apoptotic cells in db/db mice. IH and HG decreased the cell viability and the level of mitochondrial membrane potential, and increased ROS expression in H9C2 cells. These findings indicate that CIH exposure promotes glycolipid metabolism disorders and myocardial apoptosis, aggravating myocardial injury via the LKB1/AMPK/Nrf2 pathway in vitro and in vivo.

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Section: Plos Onementioning

confidence: 63%

Chronic intermittent hypoxia aggravated diabetic cardiomyopathy through LKB1/AMPK/Nrf2 signaling pathway

Liu,

Si,

et al. 2024

PLoS ONE

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“…On the other hand, AM251, another CB 1 R antagonist, which was started 24 h after AMI and continued for 12 weeks, failed to affect infarct size but promoted cardiac remodeling ( Wagner et al, 2003 ). The same drug, however, reduced the damage of murine cardiomyocytes undergoing hypoxia by decreasing apoptosis, oxidative stress and mitochondrial injury ( Hu et al, 2023 ). Incubation of murine atrial cardiomyocytes with rimonabant failed to inhibit cell death during H/R ( Lim et al, 2009 ).…”

Section: Cardioprotection In Experimental Myocardial Ischemia/reperus...mentioning

confidence: 99%

“…The results regarding the role of CB 1 Rs in I/R injury are inconsistent. It has already been mentioned above that studies with CB 1 R antagonists suggest that CB 1 Rs have a beneficial ( Lim et al, 2009 )– in vivo experiments only; ( Wagner et al, 2003 ; Slavic et al, 2013 );] or detrimental effect ( Hu et al, 2023 ) or no effect at all [( Lim et al, 2009 )– in vitro experiments only)].…”

Section: Cardioprotection In Experimental Myocardial Ischemia/reperus...mentioning

confidence: 99%

“…In an in vitro study, the anti-fibrotic and anti-oxidative actions of CB 2 R activation leading to the inhibition of the TGF-β1/Smad3 pathway was shown ( Li et al, 2016 ). Blockade of CB 1 Rs with AM251 reduced the damage of cardiomyocytes exposed to hypoxia by activation of the AMPK pathway ( Hu et al, 2023 ). With respect to the cannabidiol-dependent cardioprotective actions against I/R injury, the PI3K/Akt and MAPK/ERK pathways were shown as the only cellular mechanisms ( Franco-Vadillo et al, 2021 ).…”

Section: Potential Cellular Mechanisms Of Cardioprotective Actions Of...mentioning

confidence: 99%

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Re-evaluation of the cardioprotective effects of cannabinoids against ischemia-reperfusion injury according to the IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) criteria

Pędzińska-Betiuk,

Schlicker,

Weresa

et al. 2024

Front. Pharmacol.

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Ischemic heart disease, associated with high morbidity and mortality, represents a major challenge for the development of drug-based strategies to improve its prognosis. Results of pre-clinical studies suggest that agonists of cannabinoid CB2 receptors and multitarget cannabidiol might be potential cardioprotective strategies against ischemia-reperfusion injury. The aim of our study was to re-evaluate the cardioprotective effects of cannabinoids against ischemia-reperfusion injury according to the IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) criteria published recently by the European Union (EU) CARDIOPROTECTION COST ACTION. To meet the minimum criteria of those guidelines, experiments should be performed (i) on healthy small animals subjected to ischemia with reperfusion lasting for at least 2 hours and (ii) confirmed in small animals with comorbidities and co-medications and (iii) in large animals. Our analysis revealed that the publications regarding cardioprotective effects of CB2 receptor agonists and cannabidiol did not meet all three strict steps of IMPACT. Thus, additional experiments are needed to confirm the cardioprotective activities of (endo)cannabinoids mainly on small animals with comorbidities and on large animals. Moreover, our publication underlines the significance of the IMPACT criteria for a proper planning of preclinical experiments regarding cardiac ischemia-reperfusion injury.

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Regulation of the CB1R/AMPK/PGC-1α signaling pathway in mitochondria of mouse hearts and cardiomyocytes with chronic intermittent hypoxia

Cited by 2 publications

References 70 publications

Chronic intermittent hypoxia aggravated diabetic cardiomyopathy through LKB1/AMPK/Nrf2 signaling pathway

Chronic intermittent hypoxia aggravated diabetic cardiomyopathy through LKB1/AMPK/Nrf2 signaling pathway

Re-evaluation of the cardioprotective effects of cannabinoids against ischemia-reperfusion injury according to the IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) criteria

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