Oxidized low-density lipoproteins and its connection with dyslipidemia, inflammatory markers, and oxidative stress in patients with occupational chronic obstructive pulmonary disease

The role of low-density oxidized lipoproteins (OxLDL) in the pathogenesis of occupational chronic obstructive pulmonary disease (COPD) is not understood well enough.

The study aims to determine the serum levels of oxidized low-density lipoproteins and their relationship with lipid profile, the level of oxidative stress and level C-reactive protein in patients with occupational chronic obstructive pulmonary disease.

Methods. 116 patients diagnosed with occupational COPD and 25 patients with no respiratory diseases (comparison group) were examined. Serum levels of OxLDL was determined by solid phase enzyme-linked immunosorbent assay (ELISA) using the commercial reagent kit MDA-oxLDL from Biomedica Gruppe, Austria.

Results. Circulating OxLDL was detected in serum in a significant proportion of patients with stable occupational COPD. In most of the patients, the concentration of OxLDL was within the values observed in the comparison group or exceeded them by no more than two times. In the minority of patients with occupational COPD (16.5%), the concentration of OxLDL was high and 4 – 10 times higher than its average value in the comparison group. It can be assumed that the revealed differences in the concentration of OxLDL are due to the different degree and intensity of oxidation of low-density lipoproteins. The relationships between OxLDL and lipid metabolism, oxidative stress (OS), the antioxidant capacity of serum (AOS), and serum levels of C-reactive protein were described.

Conclusion. Serum OxLDL levels in patients with occupational COPD, the relationship between OxLDL and lipid metabolism, oxidative stress, and inflammation will provide an expanded view of the pathogenetic aspects of occupational COPD.

1. Shen Y., Yang T., Guo S. et al. Increased serum ox-LDL levels correlated with lung function, inflammation, and oxidative stress in COPD. Mediators Inflamm. 2013; 2013: 972347. DOI: 10.1155/2013/972347.

2. Can U., Yerlikaya F.H., Yosunkaya S. Role of oxidative stress and serum lipid levels in stable chronic obstructive pulmonary disease. J. Chin. Med. Assoc. 2015; 78 (12): 702–708. DOI: 10.1016/j.jcma.2015.08.004.

3. Mazière C., Mazière J.C. Activation of transcription factors and gene expression by oxidized low-density lipoprotein. Free Radic. Biol. Med. 2009; 46 (2): 127–137. DOI: 10.1016/j.freeradbiomed.2008.10.024.

4. Greig F.H., Kennedy S., Spickett C.M. Physiological effects of oxidized phospholipids and their cellular signaling mechanisms in inflammation. Free Radic. Biol. Med. 2012; 52 (2): 266–280. DOI: 10.1016/j.freeradbiomed.2011.10.481.

5. Sedgwick J.B., Hwang Y.S., Gerbyshak H.A. et al. Oxidized low-density lipoprotein activates migration and degranulation of human granulocytes. Am. J. Respir. Cell. Mol. Biol. 2003; 29 (6): 702–709. DOI: 10.1165/rcmb.2002-0257OC.

6. Lee H.S., Song C.Y. Oxidized low-density lipoprotein and oxidative stress in the development of glomerulosclerosis. Am. J. Nephrol. 2009; 29 (1): 62–70. DOI: 10.1159/000151277.

7. Chuchalin A.G. [A role of nitric oxide for the modern clinical practice: A scientific report at the 5th Pan-Russian Congress on pulmonary hypertension, December 13, 2017]. Pul’monologiya. 2018; 28 (4): 503–511. DOI: 10.18093/0869-0189-2018-28-4-503-511 (in Russian).

8. Karoli N.A., Rebrov A.P. [Endothelial damage and functional state of the vascular wall in chronic obstructive pulmonary disease]. Klinicheskaya meditsina. 2018; 96 (6): 527–536. DOI: 10.18821/0023-2149-2018-96-6-527-536 (in Russian).

9. Levitan I., Volkov S., Subbaiah P.V. Oxidized LDL: diversity, patterns of recognition, and pathophysiology. Antioxid. Redox. Signal. 2010; 13 (1): 39–75. DOI: 10.1089/ars.2009.2733.

10. Rahman I., Adcock I.M. Oxidative stress and redox regulation of lung inflammation in COPD. Eur. Respir. J. 2006; 28 (1): 219–242. DOI: 10.1183/09031936.06.00053805.

11. Hiki M., Shimada K., Ohmura H. et al. Serum levels of remnant lipoprotein cholesterol and oxidized low-density lipoprotein in patients with coronary artery disease. J. Cardiol. 2009; 53 (1): 108–116. DOI: 10.1016/j.jjcc.2008.09.010.

12. Yeh M., Cole A.L., Choi J. et al. Role for sterol regulatory element-binding protein in activation of endothelial cells by phospholipid oxidation products. Circ. Res. 2004; 95 (8): 780–788. DOI: 10.1161/01.RES.0000146030.53089.18.

13. Lu M., Gursky O. Aggregation and fusion of low-density lipoproteins in vivo and in vitro. Biomol. Concepts. 2013; 4 (5): 501–518. DOI: 10.1515/bmc-2013-0016.

14. Steinberg D., Witztum J.L. Oxidized low-density lipoprotein and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2010; 30 (12): 2311–2316. DOI: 10.1161/ATVBAHA.108.179697.

15. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2017 Report. Available at: https://goldcopd.org [Accessed: 10.06.18].

16. Izmerov N.F., Chuchalin A.G., eds. [Occupational Respiratory Diseases. National Handbook]. Moscow: GEOTAR-Media; 2015 (in Russian).

17. Itabe H., Mori M., Fujimoto Y. et al. Minimally modified LDL is an oxidized LDL enriched with oxidized phosphatidylcholines. J. Biochem. 2003; 134 (3): 459–465. DOI: 10.1093/jb/mvg164.

18. Lu J., Jiang W., Yang J.H. et al. Electronegative LDL impairs vascular endothelial cell integrity in diabetes by disrupting fibroblast growth factor 2 (FGF2) autoregulation. Diabetes. 2008; 57 (1): 158–166. DOI: 10.2337/db07-1287.