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Alterations in left ventricular function during intermittent hypoxia: Possible involvement of O-GlcNAc protein and MAPK signaling.

Guo X, Shang J, Deng Y, Yuan X, Zhu D, Liu H - Int. J. Mol. Med. (2015)

Bottom Line: IH induced a significant increase in blood pressure, associated with a gradually abnormal myocardial architecture.In parallel, compared with exposure to normoxia, 4 weeks of IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in the levels of myocardial nuclear factor-κB (NF-κB), inflammatory cytokines, caspase-3 and cardiomyocyte apoptosis.Taken together, our suggest a possible involvement of O-GlcNAc protein and MAPK signaling in the alterations of left ventricular function and cardiac injury following IH.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, Key Laboratory of Respiratory Disease of the Ministry of Health, Wuhan 430030, P.R. China.

ABSTRACT
Obstructive sleep apnea, characterized by recurrent episodes of hypoxia [intermittent hypoxia (IH)], has been identified as a risk factor for cardiovascular diseases. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) of proteins has important regulatory implications on the pathophysiology of cardiovascular disorders. In this study, we examined the role of O-GlcNAcylation in cardiac architecture and left ventricular function following IH. Rats were randomly assigned to a normoxia and IH group (2 min 21% O2; 2 min 6-8% O2). Left ventricular function, myocardial morphology and the levels of signaling molecules were then measured. IH induced a significant increase in blood pressure, associated with a gradually abnormal myocardial architecture. The rats exposed to 2 or 3 weeks of IH presented with augmented left ventricular systolic and diastolic function, which declined at week 4. Consistently, the O-GlcNAc protein and O-GlcNAcase (OGA) levels in the left ventricular tissues steadily increased following IH, reaching peak levels at week 3. The O-GlcNAc transferase (OGT), extracellular signal-regulated kinase 1/2 (ERK1/2) and the p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation levels were affected in an opposite manner. The phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) remained unaltered. In parallel, compared with exposure to normoxia, 4 weeks of IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in the levels of myocardial nuclear factor-κB (NF-κB), inflammatory cytokines, caspase-3 and cardiomyocyte apoptosis. Taken together, our suggest a possible involvement of O-GlcNAc protein and MAPK signaling in the alterations of left ventricular function and cardiac injury following IH.

No MeSH data available.


Related in: MedlinePlus

Experimental protocols and changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP) and heart rate (HR). (A) Each cycle of intermittent hypoxia (IH) consisted of a 2-min episode of hypoxia (FiO2 6–8%) and a 2-min period of reoxygenation (FiO2 21%). Arterial blood gases were measured at baseline (C0), during the nadir hypoxic portion of the cycle (I2) and at the peak of the air flush (C2). *P<0.05 vs. C0; #P<0.05 vs. C2. (B) Changes in MABP, SBP, DBP and HR in the rats exposed to normoxia or IH. Data are the means ± SD. *P<0.05 vs. corresponding values of the control group (normoxia); #P<0.05 vs. corresponding baseline values.
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f1-ijmm-36-01-0150: Experimental protocols and changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP) and heart rate (HR). (A) Each cycle of intermittent hypoxia (IH) consisted of a 2-min episode of hypoxia (FiO2 6–8%) and a 2-min period of reoxygenation (FiO2 21%). Arterial blood gases were measured at baseline (C0), during the nadir hypoxic portion of the cycle (I2) and at the peak of the air flush (C2). *P<0.05 vs. C0; #P<0.05 vs. C2. (B) Changes in MABP, SBP, DBP and HR in the rats exposed to normoxia or IH. Data are the means ± SD. *P<0.05 vs. corresponding values of the control group (normoxia); #P<0.05 vs. corresponding baseline values.

Mentions: Over the course of exposure to IH consisting of 2 min of hypoxia followed by 2 min of re-oxygenation, arterial blood gases withdrawn during the most hypoxic portion of the cycle showed a nadir hypoxia within the range of severe OSA, which recovered to the baseline PaO2 during the air flush (Fig. 1A). Baseline blood pressure parameters [mean arterial blood pressure (MABP), systolic blood pressure (SBP), diastolic blood pressure (DBP)] and HR were similar between the 2 groups. Exposure to IH for 2 weeks evoked a significant increase in MABP, SBP and DBP, which remained elevated until the end of the 4-week duration of exposure to IH. However, exposure to normoxia failed to cause any significant changes in blood pressure parameters with time. However, neither exposure to normoxia nor IH markedly altered the rats HR during the same observation period (Fig. 1B).


Alterations in left ventricular function during intermittent hypoxia: Possible involvement of O-GlcNAc protein and MAPK signaling.

Guo X, Shang J, Deng Y, Yuan X, Zhu D, Liu H - Int. J. Mol. Med. (2015)

Experimental protocols and changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP) and heart rate (HR). (A) Each cycle of intermittent hypoxia (IH) consisted of a 2-min episode of hypoxia (FiO2 6–8%) and a 2-min period of reoxygenation (FiO2 21%). Arterial blood gases were measured at baseline (C0), during the nadir hypoxic portion of the cycle (I2) and at the peak of the air flush (C2). *P<0.05 vs. C0; #P<0.05 vs. C2. (B) Changes in MABP, SBP, DBP and HR in the rats exposed to normoxia or IH. Data are the means ± SD. *P<0.05 vs. corresponding values of the control group (normoxia); #P<0.05 vs. corresponding baseline values.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494595&req=5

f1-ijmm-36-01-0150: Experimental protocols and changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP) and heart rate (HR). (A) Each cycle of intermittent hypoxia (IH) consisted of a 2-min episode of hypoxia (FiO2 6–8%) and a 2-min period of reoxygenation (FiO2 21%). Arterial blood gases were measured at baseline (C0), during the nadir hypoxic portion of the cycle (I2) and at the peak of the air flush (C2). *P<0.05 vs. C0; #P<0.05 vs. C2. (B) Changes in MABP, SBP, DBP and HR in the rats exposed to normoxia or IH. Data are the means ± SD. *P<0.05 vs. corresponding values of the control group (normoxia); #P<0.05 vs. corresponding baseline values.
Mentions: Over the course of exposure to IH consisting of 2 min of hypoxia followed by 2 min of re-oxygenation, arterial blood gases withdrawn during the most hypoxic portion of the cycle showed a nadir hypoxia within the range of severe OSA, which recovered to the baseline PaO2 during the air flush (Fig. 1A). Baseline blood pressure parameters [mean arterial blood pressure (MABP), systolic blood pressure (SBP), diastolic blood pressure (DBP)] and HR were similar between the 2 groups. Exposure to IH for 2 weeks evoked a significant increase in MABP, SBP and DBP, which remained elevated until the end of the 4-week duration of exposure to IH. However, exposure to normoxia failed to cause any significant changes in blood pressure parameters with time. However, neither exposure to normoxia nor IH markedly altered the rats HR during the same observation period (Fig. 1B).

Bottom Line: IH induced a significant increase in blood pressure, associated with a gradually abnormal myocardial architecture.In parallel, compared with exposure to normoxia, 4 weeks of IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in the levels of myocardial nuclear factor-κB (NF-κB), inflammatory cytokines, caspase-3 and cardiomyocyte apoptosis.Taken together, our suggest a possible involvement of O-GlcNAc protein and MAPK signaling in the alterations of left ventricular function and cardiac injury following IH.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, Key Laboratory of Respiratory Disease of the Ministry of Health, Wuhan 430030, P.R. China.

ABSTRACT
Obstructive sleep apnea, characterized by recurrent episodes of hypoxia [intermittent hypoxia (IH)], has been identified as a risk factor for cardiovascular diseases. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) of proteins has important regulatory implications on the pathophysiology of cardiovascular disorders. In this study, we examined the role of O-GlcNAcylation in cardiac architecture and left ventricular function following IH. Rats were randomly assigned to a normoxia and IH group (2 min 21% O2; 2 min 6-8% O2). Left ventricular function, myocardial morphology and the levels of signaling molecules were then measured. IH induced a significant increase in blood pressure, associated with a gradually abnormal myocardial architecture. The rats exposed to 2 or 3 weeks of IH presented with augmented left ventricular systolic and diastolic function, which declined at week 4. Consistently, the O-GlcNAc protein and O-GlcNAcase (OGA) levels in the left ventricular tissues steadily increased following IH, reaching peak levels at week 3. The O-GlcNAc transferase (OGT), extracellular signal-regulated kinase 1/2 (ERK1/2) and the p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation levels were affected in an opposite manner. The phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) remained unaltered. In parallel, compared with exposure to normoxia, 4 weeks of IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in the levels of myocardial nuclear factor-κB (NF-κB), inflammatory cytokines, caspase-3 and cardiomyocyte apoptosis. Taken together, our suggest a possible involvement of O-GlcNAc protein and MAPK signaling in the alterations of left ventricular function and cardiac injury following IH.

No MeSH data available.


Related in: MedlinePlus