The long non-coding RNA MALAT1 is upregulated in myocardial tissue exposed to intermittent hypoxia_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

CHEN Fengwei , ZHANG Cheng , DONG Hui , WANG Qimin ,  MA Jing , WANG Guangfa

Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing 100034, P. R. China;

Corresponding author：

MA Jing, Email: majjmail@163.com

Keywords：

Obstructive sleep apnea; Long non-coding RNA; Intermitted hypoxia; Hypercapnia; Inflammation

DOI：

10.7507/1671-6205.201710025

Video：

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Abstract Full text Figures/Tables Video References Cited by

ObjectiveBy detecting the expression of the long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in myocardial tissue under different hypoxia patterns, to explore the possible mechanism of obstructive sleep apnea (OSA)-induced cardiovascular diseases.MethodsSD rats were randomly and equally divided into 4 groups namely a normal (N) group, a continuous hypoxia (CH) group, an intermittent hypoxia (IH) group and an intermittent hypoxia with hypercapnia (IHH) group, and were treated for 1, 2, and 3 weeks. The expression of MALAT1 and associated immune factors of the myocardial tissue were examined by qRT-PCR.ResultsAn elevation without significance was observed in those three hypoxia groups in contrast with N group after 1 week’s treatment. However, in 2 and 3 weeks’ groups, the mRNA expression of MALAT1 was significantly higher in IHH group than the other three groups (all P<0.01), while there was no significant difference among IH, CH or N groups despite an increasing tendency in IH and CH groups against N group were observed. Additionally, the expressions of hypoxia inducible factor-1α (P<0.05), Toll-like receptor 4 (P<0.01) and interleukin-6 (P<0.05) mRNA were also increased significantly in IHH group compared with IH, CH and IHH groups in 3 weeks’ treatment respectively, which were coordinated with the change of MALAT1 mRNA.ConclusionsThe expression of MALAT1 in myocardial tissue is elevated by intermittent hypoxia with hypercapnia, and the tendency is similar with hypoxia-induced inflammation factors. These findings indicate that MALAT1 is probably a regulatory factor of OSA induced myocardial immune injury.

Citation： CHEN Fengwei, ZHANG Cheng, DONG Hui, WANG Qimin, MA Jing, WANG Guangfa. The long non-coding RNA MALAT1 is upregulated in myocardial tissue exposed to intermittent hypoxia. Chinese Journal of Respiratory and Critical Care Medicine, 2018, 17(4): 377-382. doi: 10.7507/1671-6205.201710025 Copy

1.	Drager LF, Togeiro SM, Polotsky VY, et al. Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome. J Am Coll Cardiol, 2013, 62(7): 569-576.
2.	Crifo B, Taylor CT. Crosstalk between toll-like receptors and hypoxia-dependent pathways in health and disease. J Investig Med, 2016, 64(2): 369-375.
3.	Unnikrishnan D, Jun J, Polotsky V. Inflammation in sleep apnea: an update. Rev Endocr Metab Disord, 2015, 16(1): 25-34.
4.	Chen YG, Satpathy AT, Chang HY. Gene regulation in the immune system by long noncoding RNAs. Nat Immunol, 2017, 18(9): 962-972.
5.	Mazidi M, Penson P, Gluba-Brzozka A, et al. Relationship between long noncoding RNAs and physiological risk factors of cardiovascular disease. J Clin Lipidol, 2017, 11(3): 617-623.
6.	Boon RA, Jae N, Holdt L, et al. Long Noncoding RNAs: From Clinical Genetics to Therapeutic Targets?. J Am Coll Cardiol, 2016, 67(10): 1214-1226.
7.	Tripathi V, Ellis JD, Shen Z, et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell, 2010, 39(6): 925-938.
8.	Tripathi V, Shen Z, Chakraborty A, et al. Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet, 2013, 9(3): e1003368.
9.	Michalik KM, You X, Manavski Y, et al. Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res, 2014, 114(9): 1389-1397.
10.	Luo F, Liu X, Ling M, et al. The lncRNA MALAT1, acting through HIF-1alpha stabilization, enhances arsenite-induced glycolysis in human hepatic L-02 cells. Biochim Biophys Acta, 2016, 1862(9): 1685-1695.
11.	Salle-Lefort S, Miard S, Nolin MA, et al. Hypoxia upregulates Malat1 expression through a CaMKK/AMPK/HIF-1alpha axis. Int J Oncol, 2016, 49(4): 1731-1736.
12.	Liu JY, Yao J, Li XM, et al. Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus. Cell Death Dis, 2014, 5(10): e1506.
13.	Lelli A, Nolan KA, Santambrogio S, et al. Induction of long noncoding RNA MALAT1 in hypoxic mice. Hypoxia(Auckl), 2015, 3(default): 45-52.
14.	Vausort M, Wagner DR, Devaux Y. Long noncoding RNAs in patients with acute myocardial infarction. Circ Res, 2014, 115(7): 668-677.
15.	Puthanveetil P, Chen S, Feng B, et al. Long non-coding RNA MALAT1 regulates hyperglycaemia induced inflammatory process in the endothelial cells. J Cell Mol Med, 2015, 19(6): 1418-1425.
16.	Zhao G, Su Z, Song D, et al. The long noncoding RNA MALAT1 regulates the lipopolysaccharide-induced inflammatory response through its interaction with NF-kappaB. FEBS Lett, 2016, 590(17): 2884-2895.
17.	Zhuang YT, Xu DY, Wang GY, et al. IL-6 induced lncRNA MALAT1 enhances TNF-alpha expression in LPS-induced septic cardiomyocytes via activation of SAA3. Eur Rev Med Pharmacol Sci, 2017, 21(2): 302-309.
18.	Zhang X, Tang X, Liu K, et al. Long Noncoding RNA Malat1 Regulates Cerebrovascular Pathologies in Ischemic Stroke. J Neurosci, 2017, 37(7): 1797-1806.
19.	Curley G, Laffey JG, Kavanagh BP. Bench-to-bedside review: carbon dioxide. Crit Care, 2010, 14(2): 220.
20.	Yamaguchi T, Yamazaki T, Nakamura Y, et al. Percutaneous carbon dioxide mist treatment has protective effects in experimental myocardial infarction. J Pharmacol Sci, 2015, 127(4): 474-480.
21.	Laffey JG, Honan D, Hopkins N, et al. Hypercapnic acidosis attenuates endotoxin-induced acute lung injury. Am J Respir Crit Care Med, 2004, 169(1): 46-56.
22.	Brzecka A. Role of hypercapnia in brain oxygenation in sleep-disordered breathing. Acta Neurobiol Exp(Wars), 2007, 67(2): 197-206.
23.	Amato MB, Barbas CS, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med, 1998, 338(6): 347-354.
24.	Dergacheva O, Dyavanapalli J, Pinol RA, et al. Chronic intermittent hypoxia and hypercapnia inhibit the hypothalamic paraventricular nucleus neurotransmission to parasympathetic cardiac neurons in the brain stem. Hypertension, 2014, 64(3): 597-603.
25.	Cummins EP, Oliver KM, Lenihan CR, et al. NF-kappaB links CO2 sensing to innate immunity and inflammation in mammalian cells. J Immunol, 2010, 185(7): 4439-4445.
26.	Abolhassani M, Guais A, Chaumet-Riffaud P, et al. Carbon dioxide inhalation causes pulmonary inflammation. Am J Physiol Lung Cell Mol Physiol, 2009, 296(4): L657-665.
27.	Nichol AD, O'Cronin DF, Howell K, et al. Infection-induced lung injury is worsened after renal buffering of hypercapnic acidosis. Crit Care Med, 2009, 37(11): 2953-2961.
28.	Hanly EJ, Mendoza-Sagaon M, Murata K, et al. CO2 pneumoperitoneum modifies the inflammatory response to sepsis. Ann Surg, 2003, 237(3): 343-350.

1. Drager LF, Togeiro SM, Polotsky VY, et al. Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome. J Am Coll Cardiol, 2013, 62(7): 569-576.
2. Crifo B, Taylor CT. Crosstalk between toll-like receptors and hypoxia-dependent pathways in health and disease. J Investig Med, 2016, 64(2): 369-375.
3. Unnikrishnan D, Jun J, Polotsky V. Inflammation in sleep apnea: an update. Rev Endocr Metab Disord, 2015, 16(1): 25-34.
4. Chen YG, Satpathy AT, Chang HY. Gene regulation in the immune system by long noncoding RNAs. Nat Immunol, 2017, 18(9): 962-972.
5. Mazidi M, Penson P, Gluba-Brzozka A, et al. Relationship between long noncoding RNAs and physiological risk factors of cardiovascular disease. J Clin Lipidol, 2017, 11(3): 617-623.
6. Boon RA, Jae N, Holdt L, et al. Long Noncoding RNAs: From Clinical Genetics to Therapeutic Targets?. J Am Coll Cardiol, 2016, 67(10): 1214-1226.
7. Tripathi V, Ellis JD, Shen Z, et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell, 2010, 39(6): 925-938.
8. Tripathi V, Shen Z, Chakraborty A, et al. Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet, 2013, 9(3): e1003368.
9. Michalik KM, You X, Manavski Y, et al. Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res, 2014, 114(9): 1389-1397.
10. Luo F, Liu X, Ling M, et al. The lncRNA MALAT1, acting through HIF-1alpha stabilization, enhances arsenite-induced glycolysis in human hepatic L-02 cells. Biochim Biophys Acta, 2016, 1862(9): 1685-1695.
11. Salle-Lefort S, Miard S, Nolin MA, et al. Hypoxia upregulates Malat1 expression through a CaMKK/AMPK/HIF-1alpha axis. Int J Oncol, 2016, 49(4): 1731-1736.
12. Liu JY, Yao J, Li XM, et al. Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus. Cell Death Dis, 2014, 5(10): e1506.
13. Lelli A, Nolan KA, Santambrogio S, et al. Induction of long noncoding RNA MALAT1 in hypoxic mice. Hypoxia(Auckl), 2015, 3(default): 45-52.
14. Vausort M, Wagner DR, Devaux Y. Long noncoding RNAs in patients with acute myocardial infarction. Circ Res, 2014, 115(7): 668-677.
15. Puthanveetil P, Chen S, Feng B, et al. Long non-coding RNA MALAT1 regulates hyperglycaemia induced inflammatory process in the endothelial cells. J Cell Mol Med, 2015, 19(6): 1418-1425.
16. Zhao G, Su Z, Song D, et al. The long noncoding RNA MALAT1 regulates the lipopolysaccharide-induced inflammatory response through its interaction with NF-kappaB. FEBS Lett, 2016, 590(17): 2884-2895.
17. Zhuang YT, Xu DY, Wang GY, et al. IL-6 induced lncRNA MALAT1 enhances TNF-alpha expression in LPS-induced septic cardiomyocytes via activation of SAA3. Eur Rev Med Pharmacol Sci, 2017, 21(2): 302-309.
18. Zhang X, Tang X, Liu K, et al. Long Noncoding RNA Malat1 Regulates Cerebrovascular Pathologies in Ischemic Stroke. J Neurosci, 2017, 37(7): 1797-1806.
19. Curley G, Laffey JG, Kavanagh BP. Bench-to-bedside review: carbon dioxide. Crit Care, 2010, 14(2): 220.
20. Yamaguchi T, Yamazaki T, Nakamura Y, et al. Percutaneous carbon dioxide mist treatment has protective effects in experimental myocardial infarction. J Pharmacol Sci, 2015, 127(4): 474-480.
21. Laffey JG, Honan D, Hopkins N, et al. Hypercapnic acidosis attenuates endotoxin-induced acute lung injury. Am J Respir Crit Care Med, 2004, 169(1): 46-56.
22. Brzecka A. Role of hypercapnia in brain oxygenation in sleep-disordered breathing. Acta Neurobiol Exp(Wars), 2007, 67(2): 197-206.
23. Amato MB, Barbas CS, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med, 1998, 338(6): 347-354.
24. Dergacheva O, Dyavanapalli J, Pinol RA, et al. Chronic intermittent hypoxia and hypercapnia inhibit the hypothalamic paraventricular nucleus neurotransmission to parasympathetic cardiac neurons in the brain stem. Hypertension, 2014, 64(3): 597-603.
25. Cummins EP, Oliver KM, Lenihan CR, et al. NF-kappaB links CO2 sensing to innate immunity and inflammation in mammalian cells. J Immunol, 2010, 185(7): 4439-4445.
26. Abolhassani M, Guais A, Chaumet-Riffaud P, et al. Carbon dioxide inhalation causes pulmonary inflammation. Am J Physiol Lung Cell Mol Physiol, 2009, 296(4): L657-665.
27. Nichol AD, O'Cronin DF, Howell K, et al. Infection-induced lung injury is worsened after renal buffering of hypercapnic acidosis. Crit Care Med, 2009, 37(11): 2953-2961.
28. Hanly EJ, Mendoza-Sagaon M, Murata K, et al. CO2 pneumoperitoneum modifies the inflammatory response to sepsis. Ann Surg, 2003, 237(3): 343-350.

Chinese Journal of Respiratory and Critical Care Medicine

The long non-coding RNA MALAT1 is upregulated in myocardial tissue exposed to intermittent hypoxia

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