Effects of long-term intermittent hypoxia on mitochondrial and Fas death receptor dependent apoptotic pathways in rat hearts

Lee, Shin-Da; Kuo, Wei Wen; Lin, James A.; Chu, Yu Fang; Wang, Chin Kun; Yeh, Yu Lan; Wang, Shyi Gang P; Liu, Jer Yuh; Chang, Mu Hsin; Huang, Chih Yang

doi:10.1016/j.ijcard.2006.03.064

Cited by 45 publications

(39 citation statements)

References 18 publications

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“…The myocardium subsequently exhibits an increase in ventricular wall thickness, myocardial architecture changes [11] and myocardial interstitial space expansion. These events lead to ventricular dysfunction [12]. This phenomenon is similar to hypertension, resulting in ventricular hypertrophy [13].…”

Section: Introductionmentioning

confidence: 99%

Differences in left ventricular cardiomyocyte loss induced by chronic intermittent hypoxia between spontaneously hypertensive and Wistar–Kyoto rats

et al. 2010

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Section: Introductionmentioning

confidence: 99%

Differences in left ventricular cardiomyocyte loss induced by chronic intermittent hypoxia between spontaneously hypertensive and Wistar–Kyoto rats

et al. 2010

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“…6,7 Cardiac apoptosis was found in many chronic metabolic and cardiovascular diseases such as obesity, 8,9 diabetes, and hypertension, 7,10 and in various stressful conditions, such as long-term hypoxia, 8,11 or smoke. 12 The occurrence of apoptosis has been often reported to contribute to the loss of cardiomyocytes in myocardial diseases, and is recognized as a predictor of adverse outcomes in patients with cardiac diseases or heart failure.…”

Section: Introductionmentioning

confidence: 99%

Effects of insulin replacement on cardiac apoptotic and survival pathways in streptozotocin‐induced diabetic rats

Kuo

Chung

Liu

et al. 2009

Cell Biochemistry & Function

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Increased myocyte apoptosis in diabetic hearts has been previously reported. Therefore, the purpose of this study was to evaluate the effects of insulin on cardiac apoptotic, hypertrophic, and survival pathways in streptozotocin (STZ)-induced diabetic rats. Forty-eight male Wistar rats at 8 weeks of age were randomly divided into control group (Control), STZ-induced (65 mg/kg STZ i.v.) Type 1-like diabetic rats (DM), and DM rats with 4 IU insulin replacement (DI) for 4 and 8 weeks, respectively. The levels of protein involved in cardiac apoptotic, hypertrophic, and survival pathways were measured by Western blotting. Cardiac mitochondrial-dependent apoptotic pathways, such as Bad, cytosolic cytochrome c, activated caspase 9 and 3, and calcineurin-nuclear factor activation transcription 3 (NFAT3) hypertrophic pathway in DM were increased compared to Control and attenuated in DI group after 8 weeks whereas those were not found after 4 weeks. Cardiac anti-apoptotic Bcl2 and phosphorylated-Bad were significantly decreased in DM group but not in DI group after 8 weeks. Insulin-like growth factor-I receptor (IGFIR), phosphatidylinositol 3'-kinase (PI3K), and the protein kinase B (Akt) were significantly decreased in DM relative to Control and DI after 8 weeks whereas those were not found after 4 weeks. Insulin replacement not only prevents activation of the cardiac mitochondrial-dependent apoptotic pathway and calcineurin-related NFAT3 hypertrophic pathway in diabetes but it also enhances the cardiac insulin/IGFIR-PI3K-Akt survival pathway, all of which are attenuated with insulin therapeutic duration-dependent manners. The findings may provide possible diabetes-related apoptotic, hypertrophic, and survival pathways for potentially preventing cardiac abnormality in diabetes.

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“…When cytochrome c is released from mitochondria into cytosol, it is responsible for activating caspase-9, which further activates caspase-3 and executes the apoptotic program (9). One of our previous studies showed that longer duration of nocturnal sustained hypoxia at 0-, 4-, and 8-wk periods appeared to exert more deleterious effects on Fas and mitochondrial-dependent apoptotic pathways in Sprague-Dawley rats (20,21). The increased cardiac apoptosis was found in leptin-deficient and leptin-resistant mice (6), implying that leptin-signaling impairments may lead to cardiac apoptosis.…”

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confidence: 99%

The coexistence of nocturnal sustained hypoxia and obesity additively increases cardiac apoptosis

Lee

Kuo

Bau

et al. 2008

Journal of Applied Physiology

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. The coexistence of nocturnal sustained hypoxia and obesity additively increases cardiac apoptosis. J Appl Physiol 104: 1144-1153, 2008. First published January 17, 2008 doi:10.1152 doi:10. /japplphysiol.00152.2007 nocturnal sustained hypoxia during sleeping time has been reported in severe obesity, but no information regarding the cardiac molecular mechanism in the coexistence of nocturnal sustained hypoxia and obesity is available. This study evaluates whether the coexistence of nocturnal sustained hypoxia and obesity will increase cardiac Fas death receptor and mitochondrial-dependent apoptotic pathway. Methods: 32 lean and 32 obese 5-to 6-mo-old rats with or without nocturnal sustained hypoxia were studied and assigned to one of four subgroups: normoxia lean (NL), normoxia obese (NO), hypoxia lean (HL, 12% O2 for 8 h and 21% O2 16 h/day, 1 wk), and hypoxia obese (HO). The heart weight index, tail cuff plethysmography, echocardiography, hematoxylin-eosin staining, TUNEL assays, Western blotting, and RT-PCR were performed. Results: systolic and diastolic blood pressures in HO were higher than those in NL, and fractional shortening in HO was reduced compared with others. The whole heart weight, the left ventricular weight, the abnormal myocardial architecture, and TUNEL-positive apoptotic cells, as well as the activity of cardiac Fas-dependent and mitochondrial-dependent apoptotic pathway, were significantly increased in obese group or nocturnal sustained hypoxia group and were further increased when obesity and nocturnal sustained hypoxia coexisted, the evidence for which is based on decreases in an anti-apoptotic protein Bcl2 level and Bid and increases in Fas, FADD, pro-apoptotic Bad, BNIP3, cytosolic cytochrome c, activated caspase-8, activated caspase-9, and activated caspase-3. Conclusions: The cardiac Fas receptor-and mitochondrial-dependent apoptotic pathways were more activated in obesity with coexistent nocturnal sustained hypoxia, which may represent one possible apoptotic mechanism for the development of heart failure in obesity with nocturnal sustained hypoxia.

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Effects of long-term intermittent hypoxia on mitochondrial and Fas death receptor dependent apoptotic pathways in rat hearts

Cited by 45 publications

References 18 publications

Differences in left ventricular cardiomyocyte loss induced by chronic intermittent hypoxia between spontaneously hypertensive and Wistar–Kyoto rats

Differences in left ventricular cardiomyocyte loss induced by chronic intermittent hypoxia between spontaneously hypertensive and Wistar–Kyoto rats

Effects of insulin replacement on cardiac apoptotic and survival pathways in streptozotocin‐induced diabetic rats

The coexistence of nocturnal sustained hypoxia and obesity additively increases cardiac apoptosis

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