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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

Changes in cardiac architecture and protein expression during the 4 weeks of exposure to intermittent hypoxia (IH). (A) Histopathological analysis and expression of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in the left ventricular tissues. Gradually abnormal myocardial architecture occurred due to exposure to IH, as evidenced by cardiomyocyte disarray and structural disorganization, without significant changes in collagen deposition. OGA and OGT levels changed dynamically during the 4 weeks of exposure to IH. (B) The area of cardiac interstitial collagen prior to exposure to IH was regarded as the baseline value. (C) After 4 weeks of exposure to IH (CIH) there was a significant increase in cardiomyocyte size compared with exposure to normoxia (CON). Scale bar, 100 µm. *P<0.05 vs. normoxia group.
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f2-ijmm-36-01-0150: Changes in cardiac architecture and protein expression during the 4 weeks of exposure to intermittent hypoxia (IH). (A) Histopathological analysis and expression of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in the left ventricular tissues. Gradually abnormal myocardial architecture occurred due to exposure to IH, as evidenced by cardiomyocyte disarray and structural disorganization, without significant changes in collagen deposition. OGA and OGT levels changed dynamically during the 4 weeks of exposure to IH. (B) The area of cardiac interstitial collagen prior to exposure to IH was regarded as the baseline value. (C) After 4 weeks of exposure to IH (CIH) there was a significant increase in cardiomyocyte size compared with exposure to normoxia (CON). Scale bar, 100 µm. *P<0.05 vs. normoxia group.

Mentions: The rats in the IH group gained less body weight than the rats in the normoxia group during the 4-week period of exposure. The ratio of HW/BW and LVW/BW and the indexes of systemic hypertension-induced hypertrophy were significantly higher in the rats in the IH group. The LV tissue sections of the rats in the IH group stained with H&E showed a gradually abnormal myocardial architecture, as evidenced by an increase in cardiomyocyte diameter, cardiomyocyte disarray and structural disorganization. No signigicant changes in the interstitial collagen deposition were observed (Fig. 2 and Table I).


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)

Changes in cardiac architecture and protein expression during the 4 weeks of exposure to intermittent hypoxia (IH). (A) Histopathological analysis and expression of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in the left ventricular tissues. Gradually abnormal myocardial architecture occurred due to exposure to IH, as evidenced by cardiomyocyte disarray and structural disorganization, without significant changes in collagen deposition. OGA and OGT levels changed dynamically during the 4 weeks of exposure to IH. (B) The area of cardiac interstitial collagen prior to exposure to IH was regarded as the baseline value. (C) After 4 weeks of exposure to IH (CIH) there was a significant increase in cardiomyocyte size compared with exposure to normoxia (CON). Scale bar, 100 µm. *P<0.05 vs. normoxia group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-ijmm-36-01-0150: Changes in cardiac architecture and protein expression during the 4 weeks of exposure to intermittent hypoxia (IH). (A) Histopathological analysis and expression of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in the left ventricular tissues. Gradually abnormal myocardial architecture occurred due to exposure to IH, as evidenced by cardiomyocyte disarray and structural disorganization, without significant changes in collagen deposition. OGA and OGT levels changed dynamically during the 4 weeks of exposure to IH. (B) The area of cardiac interstitial collagen prior to exposure to IH was regarded as the baseline value. (C) After 4 weeks of exposure to IH (CIH) there was a significant increase in cardiomyocyte size compared with exposure to normoxia (CON). Scale bar, 100 µm. *P<0.05 vs. normoxia group.
Mentions: The rats in the IH group gained less body weight than the rats in the normoxia group during the 4-week period of exposure. The ratio of HW/BW and LVW/BW and the indexes of systemic hypertension-induced hypertrophy were significantly higher in the rats in the IH group. The LV tissue sections of the rats in the IH group stained with H&E showed a gradually abnormal myocardial architecture, as evidenced by an increase in cardiomyocyte diameter, cardiomyocyte disarray and structural disorganization. No signigicant changes in the interstitial collagen deposition were observed (Fig. 2 and Table I).

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