Dysfunctional high-density lipoproteins in diabetes mellitus
https://doi.org/10.14341/probl13118
Abstract
The risk of cardiovascular disease (CVD) in persons with type 2 diabetes mellitus (DM2) increases two to four times. One of the main factors increasing cardiovascular risk is dyslipidemia, which includes abnormalities in all lipoproteins, including high-density lipoproteins (HDL). The development of DM2 is accompanied not only by a decrease in the level of HDL, but also by significant changes in their structure. This leads to the transformation of native HDL into so-called dysfunctional or diabetic HDL, which loses their antiatherogenic, cardioprotective, anti-inflammatory and anti-diabetic properties. In poorly controlled diabetes mellitus HDL can not only lose its beneficial functions, but also acquire proatherogenic, proinflammatory ones. Diabetic HDL can contribute to the accumulation of such unfavorable qualities as increased proliferation, migration, and invasion of cancer cells. Given that HDL, in addition to participation in cholesterol transport, performs important regulatory functions in the body, there is reason to assume that structural modifications of HDL (oxidation, glycation, triglyceride enrichment, loss of HDL-associated enzymes, etc.) are one of the causes of vascular complications of diabetes.
About the Authors
O. N. Poteryaeva
Institute of Biochemistry, Federal Research Center of Fundamental and Translation Medicine
Russian Federation
Competing Interests:
Russian Federation
Olga N. Poteryaeva - MD, PhD.
2 Timakova str., Novosibirsk, 630117.
SPIN-код: 2140-4725
Competing Interests:
None
I. F. Usynin
Institute of Biochemistry, Federal Research Center of Fundamental and Translation Medicine
Russian Federation
Competing Interests:
Russian Federation
Ivan F. Usynin - BD, PhD.
2 Timakova str., Novosibirsk, 630117.
SPIN-код: 2772-7098
Competing Interests:
None
References
1. Dedov II, Shestakova MV, Vikulova OK, et al. Epidemiological characteristics of diabetes mellitus in Russian Federation: clinical and statistical analisis according to the Federal diabetes register data of 01.01.2021. Diabetes mellitus. 2021;24(3):204-221. (In Russ.). doi: https://doi.org/10.14341/DM12759
2. Srivastava RAK. Dysfunctional HDL in diabetes mellitus and its role in the pathogenesis of cardiovascular disease. Mol Cell Biochem. 2018;440(1-2):167-187. doi: https://doi.org/10.1007/s11010-017-3165-z
3. Vergès B. Pathophysiology of diabetic dyslipidaemia: where are we? Diabetologia. 2015;58(5):886-899. doi: https://doi.org/10.1007/s00125-015-3525-8
4. Ershova AI, Al Rashi DO, Ivanova AA, et al. Secondary hyperlipidemias: etiology and pathogenesis. Russ J Cardiol. 2019;63(5):74-81. (In Russ.). doi: https://doi.org/10.15829/1560-4071-2019-5-74-81
5. Hwang Y-C, Ahn H-Y, Park S-W, Park C-Y. Association of HDL-C and apolipoprotein A-I with the risk of type 2 diabetes in subjects with impaired fasting glucose. Eur J Endocrinol. 2014;171(1):137-142. doi: https://doi.org/10.1530/EJE-14-0195
6. Bonilha I, Zimetti F, Zanotti I, et al. Dysfunctional high-density lipoproteins in type 2 diabetes mellitus: molecular mechanisms and therapeutic implications J. Clin. Med. 2021;10(11):2233. doi: https://doi.org/10.3390/jcm10112233
7. Ahmed HM, Miller M, Nasir K, et al. Primary low level of high-density lipoprotein cholesterol and risks of coronary heart disease, cardiovascular disease, and death: results from the multi-ethnic study of atherosclerosis. Am.J.Epidemiol. 2016;183(10):875-883. doi: https://doi.org/10.1093/aje/kwv305
8. Wong N, Nicholls S, Tan J, Bursill C. The Role of High-Density Lipoproteins in Diabetes and Its Vascular Complications. Int J Mol Sci. 2018;19(6):1680. doi: https://doi.org/10.3390/ijms19061680
9. Poteryaeva ON, Usynin IF. Antidiabetic role of high density lipoproteins. Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry. 2019;13(2):113-121. (In Russ.). doi: https://doi.org/10.1134/S1990750819020070
10. Cochran BJ, Ong K-L, Manandhar B, et al. High density lipoproteins and diabetes. Cells. 2021;10(4):850. doi: https://doi.org/10.3390/cells10040850
11. Drew BG, Rye KA, Duffy SJ, et al. The emerging role of HDL in glucose metabolism. Nat Rev Endocrinol. 2012;8(4):237-245. doi: https://doi.org/10.1038/nrendo.2011.235
12. Han R, Lai R, Ding Q, et al. Apolipoprotein A-I stimulates AMP-activated protein kinase and improves glucose metabolism. Diabetologia. 2007;50(9):1960-1968. doi: https://doi.org/10.1007/s00125-007-0752-7
13. Stenkula KG, Lindahl M, Petrlova J, et al. Single injections of apoAI acutely improve in vivo glucose tolerance in insulin-resistant mice. Diabetologia. 2014;57(4):797-800. doi: https://doi.org/10.1007/s00125-014-3162-7
14. Torkhovskaya TI, Kudinov VA, Zakharova TS, et al. Dysfunctional high-density lipoproteins: role in atherogenesis and potential targets for phospholipid therapy. Kardiologiya. 2018;58(3):73-83. (in Russ.). doi: https://doi.org/10.18087/cardio.2018.3.10101
15. Estrada-Luna D, Ortiz-Rodriguez MA, Medina-Briseño L, et al. Current therapies focused on high-density lipoproteins associated with cardiovascular disease. Molecules. 2018;23(11):2730. doi: https://doi.org/10.3390/molecules23112730
16. Femlak M, Gluba-Brzózka A, Ciałkowska-Rysz A, et al. The role and function of HDL in patients with diabetes mellitus and the related cardiovascular risk. Lipids Health Dis. 2017;16(1):207. doi: https://doi.org/10.1186/s12944-017-0594-3
17. Usynin IF., Poteryaeva ON., Russkikh GS. et al. Apolipoprotein A-I stimulates secretion of Insulin and matrix metalloproteinases by islets of Langerhans. Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry. 2018;64(2):195-200. (In Russ). doi: https://doi.org/10.1134/S1990750818040091
18. Viktorinova A, Jurkovicova I, Fabryova L, et al. Abnormalities in the relationship of paraoxonase 1 with HDL and apolipoprotein a1 and their possible connection to HDL dysfunctionality in type 2 diabetes. Diabetes Res. Clin. Pract. 2018;140(2):174-182. doi: https://doi.org/10.1016/j.diabres.2018.03.055
19. Poteryaeva ON, Shevkopljas OP. Sexual characteristics of some carbohydrates and serum lipids in patients with type 2 diabetes mellitus. Medicina i obrazovanie v Sibiri. 2009;1. (in Russ.). Доступно по: http: //www.ngmu.ru/cozo/mos/article/text_full.php?id=328
20. Brites F, Martin M, Guillas I, Kontush A. Antioxidative activity of high-density lipoprotein (HDL): Mechanistic insights into potential clinical benefit. BBA Clin. 2017;8(2):66-77. doi: https://doi.org/10.1016/j.bbacli.2017.07.002
21. Kontush A, Chapman MJ. Why is HDL functionally deficient in type 2 diabetes? Curr Diab Rep. 2008;8(1):51-59. doi: https://doi.org/10.1007/s11892-008-0010-5
22. Riwanto M, Rohrer L, von Eckardstein A, et al. Dysfunctional HDL: from structure, function-relationships to biomarkers. Hand. Exp. Pharmacol. 2015;224(8):337-366. doi: https://doi.org/10.1007/978-3-319-09665-0_10.
23. Stahlman M, Fagerberg B, Adiels M, et al. Dyslipidemia, but not hyperglycemia and insulin resistance, is associated with marked alterations in the HDL lipidome in type 2 diabetic subjects in the DIWA cohort: impact on small HDL particles. Biochim Biophys Acta. 2013;1831(11):1609-1617. doi: https://doi.org/10.1016/j.bbalip.2013.07.009
24. Spasov AA, Solov’eva OA, Kuznetsova VA. Protein glycation during diabetes mellitus and the possibility of its pharmacological correction (review). Himiko-farmacevticheskij Zhurnal. 2017;51(6):3-7. (In Russ.). doi: https://doi.org/10.30906/0023-1134-2017-51-6-3-7
25. Nobecourt E, Davies MJ, Brown BE, et al. The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin:cholesterol acyltransferase. Diabetologia. 2007;50(3):643-653. doi: https://doi.org/10.1007/s00125-006-0574-z
26. Bacchetti T, Masciangelo S, Armeni T, et al. Glycation of human high density lipoprotein by methylglyoxal: effect on HDL-paraoxonase activity. Metabolism. 2014;63(3):307-311. doi: https://doi.org/10.1016/j.metabol.2013.10.013
27. Domingo-Espín J, Nilsson O, Bernfur K, et al. Site-specific glycations of apolipoprotein A-I lead to differentiated functional effects on lipid-binding and on glucose metabolism. Biochim Biophys Acta - Mol Basis Dis. 2018;1864(9):2822-2834. doi: https://doi.org/10.1016/j.bbadis.2018.05.014
28. Kashyap SR, Osme A, Ilchenko S, et al. Glycation reduces the stability of apoAI and increases HDL dysfunction in diet-controlled type 2 diabetes. J. Clin. Endocrinol. Metab. 2018;103(2):388-396. doi: https://doi.org/10.1210/jc.2017-01551
29. Morresi C, Cianfruglia L, Sartini D, et al. Effect of high glucose-induced oxidative stress on paraoxonase 2 expression and activity in Caco-2 cells. Cells. 2019;8(12):E1616. doi: https://doi.org/10.3390/cells8121616
30. Gomez Rosso L, Lhomme M, Meroño T, et al. Poor glycemic control in type 2 diabetes enhances functional and compositional alterations of small, dense HDL3c. Biochim Biophys Acta - Mol Cell Biol Lipids. 2017;1862(2):188-195. doi: https://doi.org/10.1016/j.bbalip.2016.10.014
31. Barter PJ, Cochran BJ, Rye K-A. CETP inhibition, statins and diabetes. Atherosclerosis. 2018;278(2):143-146. doi: https://doi.org/10.1016/j.atherosclerosis.2018.09.033
32. Kunutsor SK, Kieneker LM, Bakker SJL, James RW, Dullaart RPF. Incident type 2 diabetes is associated with HDL, but not with its anti-oxidant constituent - paraoxonase-1: The prospective cohort PREVEND study. Metabolism. 2017;73(2):43-51. doi: https://doi.org/10.1016/j.metabol.2017.05.004
33. Kontush A, Lindahl M, Lhomme M, et al. Structure of HDL: particle subclasses and molecular components. Handb.Exp.Pharmacol. 2015;224:3-51. doi: https://doi.org/10.1007/978-3-319-09665-0_1
34. Kubota M, Nakanishi S, Hirano M, et al. Relationship between serum cholesterol efflux capacity and glucose intolerance in Japanese Americans. J Atheroscler Thromb. 2014;21(10):1087-1097. doi: https://doi.org/10.5551/jat.24315
35. Saleheen D, Scott R, Javad S, et al. association of HDL cholesterol efflux capacity with incident coronary heart disease events: a prospective case-control study. Lancet Diabetes Endocrinol. 2015;3(7):507-513. doi: https://doi.org/10.1016/S2213-8587(15)00126-6
36. Rohatgi A, Grundy SM. Cholesterol efflux capacity as a therapeutic target: rationale and clinical implications. J. Am. Coll. Cardiol. 2015;66(20):2211-2213. doi: https://doi.org/10.1016/j.jacc.2015.09.012
37. Tsun JG, Yung S, Chau MK, et al. Cellular cholesterol transport proteins in diabetic nephropathy. PLoS ONE. 2014;9(9):e105787. doi: https://doi.org/10.1371/journal.pone.0105787
38. Machado-Lima A, Iborra RT, Pinto RS, et al. In Type 2 Diabetes Mellitus Glycated Albumin Alters Macrophage Gene Expression Impairing ABCA1-Mediated Cholesterol Efflux. J Cell Physiol. 2015;230(6):1250-1257. doi: https://doi.org/10.1002/jcp.24860
39. Nicholls SJ, Zheng L, Hazen SL. Formation of dysfunctional high-density lipoprotein by myeloperoxidase. Trends Cardiovasc. Med. 2005;15(6):212-219. doi: https://doi.org/10.1016/j.tcm.2005.06.004
40. Nobecourt E, Jacqueminet S, Hansel B, et al. Defective antioxidative activity of small dense HDL3 particles in type 2 diabetes: relationship to elevated oxidative stress and hyperglycaemia. Diabetologia, 2005;48(3):529-538. doi: https://doi.org/10.1007/s00125-004-1655-5
41. Flekac M, Skrha J, Zidkova K, et al. Paraoxonase 1 gene polymorphisms and enzyme activities in diabetes mellitus. Physiol. Res. 2008;57(5):717-726. doi: https://doi.org/10.33549/physiolres.931285
42. Shen Y, Ding FH, Sun JT, et al. Association of elevated apoA-I glycation and reduced HDL-associated paraoxonase1, 3 activity, and their interaction with angiographic severity of coronary artery disease in patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2015;14(1):52. doi: https://doi.org/10.1186/s12933-015-0221-4
43. Kota SK, Meher LK, Kota SK, et al. Implications of serum paraoxonase activity in obesity, diabetes mellitus, and dyslipidemia. Indian J. Endocrinol. Metab. 2013;17(3):402-412. doi: https://doi.org/10.4103/2230-8210.111618
44. Morgantini C, Natali A, Boldrini B, et al. Anti-inflammatory and antioxidant properties of HDLs are impaired in type 2 diabetes. Diabetes. 2011;60(10):2617-2623. doi: https://doi.org/10.2337/db11-0378
45. Rye K-A, Barter PJ. Cardioprotective functions of HDLs. J Lipid Res. 2014;55(2):168-179. doi: https://doi.org/10.1194/jlr.R039297
46. Sorrentino SA, Besler C, Rohrer L, et al. Endothelial-vasoprotective effects of high-density lipoprotein are impaired in patients with type 2 diabetes mellitus but are improved after extended-release niacin therapy. Circulation. 2010;121(1):110-122. doi: https://doi.org/10.1161/ CIRCULATIONAHA.108.836346
47. Ebtehaj S, Gruppen EG, Parvizi M, et al. The anti-infammatory function of HDL is impaired in type 2 diabetes: role of hyperglycemia, paraoxonase-1 and low grade inflammation. Cardiovasc Diabetol. 2017;16(1):132. doi: https://doi.org/10.1186/s12933-017-0613-8
48. Vaisar T, Couzens E, Hwang A, et al. Type 2 diabetes is associated with loss of HDL endothelium protective functions. PLoS One. 2018;13(3):e0192616. doi: https://doi.org/10.1371/journal.pone.0192616
49. Robert J, Osto E, von Eckardstein A. The endothelium is both a target and a barrier of HDL’s protective functions. Cells. 2021;10(5):1041. doi: https://doi.org/10.3390/cells10051041
50. Denimal D, Monier S, Brindisi MC, et al. Impairment of the ability of HDL from patients with metabolic syndrome but without diabetes mellitus to activate eNOS: correction by S1P enrichment. Arterioscler Thromb Vasc Biol. 2017;37(5):804-811. doi: https://doi.org/10.1161/ATVBAHA.117.309287
51. Spieker LE, Sudano I, Hurlimann D, et al. High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation. 2002;105(12):1399-1402. doi: https://doi.org/10.1161/01.CIR.0000013424.28206.8F
52. Mazzuferi G, Bacchetti T, Islam MO, et al. High density lipoproteins and oxidative stress in breast cancer. Lipids Health Dis. 2021;20(1):143. doi: https://doi.org/10.1186/s12944-021-01562-1
53. Huang X, He D, Ming J, et al. High-density lipoprotein of patients with breast cancer complicated with type 2 diabetes mellitus promotes cancer cells adhesion to vascular endothelium via ICAM-1 and VCAM-1 upregulation. Breast Cancer Res Treat. 2016;155(3):441-455. doi: https://doi.org/10.1007/s10549-016-3696-0
54. Kawakami A, Aikawa M, Alcaide P, Luscinskas FW, Libby P, Sacks FM. Apolipoprotein CIII Induces Expression of Vascular Cell Adhesion Molecule-1 in Vascular Endothelial Cells and Increases Adhesion of Monocytic Cells. Circulation. 2006;114(7):681-687. doi: https://doi.org/10.1161/CIRCULATIONAHA.106.622514
55. Pirillo A, Catapano AL. Pitavastatin and HDL: Effects on plasma levels and function(s). Atheroscler Suppl. 2017;27(7):e1-e9. doi: https://doi.org/10.1016/j.atherosclerosissup.2017.05.001
56. Masson W, Lobo M, Siniawski D, et al. Therapy with cholesteryl ester transfer protein (CETP) inhibitors and diabetes risk. Diabetes Metab. 2018;44(6):508-513. doi: https://doi.org/10.1016/j.diabet.2018.02.005
57. Barter PJ, Cochran BJ, Rye K-A. CETP inhibition, statins and diabetes. Atherosclerosis. 2018;278(7):143-146. doi: https://doi.org/10.1016/j.atherosclerosis.2018.09.033
58. Metelskaya VA. Functional diversity of high-density lipoproteins: finding the golden mean. Ateroscleroz. 2021;17(2):61-71. (In Russ.). doi: https://doi.org/10.52727/2078-256X-2021-17-2-61-71
59. Usynin IF, Dudarev AN, Gorodetskaya AY, et al. Apolipoprotein A-I Stimulates Cell Proliferation in Bone Marrow Cell Culture. Bull Exp Biol Med. 2018;164(3):308-311. (In Russ.). doi: https://doi.org/10.1007/s10517-018-3978-0
60. Poteryaeva ON, Usynin IF. Therapeutic approaches to restoring the antiatherogenic function of high density lipoproteins. Yakut Med J. 2021;164(3):98-103. (In Russ.). doi: https://doi.org/10.25789/YMJ.2021.75.25
Supplementary files
|
|
1. Figure 1. Structural and functional impairment of HDL in T2DM [adapted from 21] | |
| Subject | ||
| Type | Исследовательские инструменты | |
View
(205KB)
|
Indexing metadata ▾ | |
Review
For citations:
Poteryaeva O.N., Usynin I.F. Dysfunctional high-density lipoproteins in diabetes mellitus. Problems of Endocrinology. 2022;68(4):69-77. (In Russ.) https://doi.org/10.14341/probl13118
Views:
2365
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
.jpg){kind=logo}
