ЮРАК ИШЕМИК КАСАЛЛИГИДА ЯЛЛИҒЛАНИШНИНГ ЗАРДОБ БИОМАРКЕРЛАРИ ВА ЛЕЙКОТСИТЛАРНИНГ ЛИПИД АЖРАТИШ ҚОБИЛИЯТИНИ БАҲОЛАШ
Keywords:
Калит сўзлар: юрак ишемик касаллиги, биомаркерлар, ҳс-CРП, интерлейкин-6, лейкотситлар, липид ажратиш қобилияти, атеросклероз.Abstract
Резюме:Юрак ишемик касаллиги (ЙИК) замонавий кардиологиянинг энг етакчи муаммоларидан бири бўлиб, сўнгги йилларда унинг патогенези фақатгина анъанавий дислипидемия нуқтаи назаридан эмас, балки сурункали иммун-яллиғланиш жараёни контекстида фаол кўриб чиқилмоқда. Атеросклеротик пилакчаларнинг шаклланиши ва уларнинг барқарорлиги нафақат плазмадаги липидлар концентрациясига, балки периферик қон лейкотситларининг функтсионал ҳолатига ҳам бевосита боғлиқдир. Иммун ҳужайраларининг липид гомеостази бир хил эмас; энг яққол дисфунктсия тизимли яллиғланишнинг юқори даражаси фонида, лейкотситларнинг модификацияланган липопротеинларни ютиши ва уларнинг тескари липид ажратиш (секреция) қобилиятининг сусайиши кўринишида намоён бўлади.ЙИКнинг клиник кечиши (стабил кечишдан ўткир коронар синдромгача) тизимли яллиғланиш биомаркерлари (hs-CRP, IL-6, GDF-15) ва иммун ҳужайраларининг тескари липид транспорти (эффлюкс) фаоллиги ўртасидаги мувозанатга таянади. Бляшкаларнинг дестабилизацияси ва ёрилиши кўпинча лейкотситлар цитоплазмасида липид томчиларининг критик тўпланиши (кўпикли ҳужайралар фенотипи) ҳамда уларнинг деструктив ферментлар ажратиши билан боғлиқдир. Бироқ, тизимли яллиғланишнинг зардоб кўрсаткичлари ва ҳужайра даражасидаги липид ажратиш дисфунктсияси ўртасидаги ўзаро сценарийлар ва корреляциялар баҳемжиҳат ўрганилмаган ҳамда бахсли бўлиб қолмоқда. Патологик жараённинг ривожланиш механизмларини аниқлаш, клиник шаклларни эрта дифферентсиаллаш ва асоратларни башорат қилиш учун ЙИКнинг замонавий мезонларига таянган ҳолда, зардоб биомаркерлари ва лейкотситлар фенотипини кенгайтирилган лаборатор баҳолашга асосланган тадқиқотлар зарур.
References
1. Roth GA, Mensah GA, Johnson CO, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am Coll Cardiol. 2020;76(25):2982-3021.
2. Ross R. Atherosclerosis — an inflammatory disease. N Engl J Med. 1999;340(2):115-126.
3. Libby P. Inflammation in atherosclerosis. Nature. 2002;420(6917):868-874.
4. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119-1131.
5. Tardif JC, Kouz S, Waters DD, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019;381(26):2497-2505.
6. Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in patients with chronic coronary disease. N Engl J Med. 2020;383(19):1838-1847.
7. Rader DJ, Hovingh GK. HDL and cardiovascular disease. Lancet. 2014;384(9943):618-625.
8. Voight BF, Peloso GM, Orho-Melander M, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet. 2012;380(9841):572-580.
9. Khera AV, Cuchel M, de la Llera-Moya M, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med. 2011;364(2):127-135.
10. Rohatgi A, Khera A, Berry JD, et al. HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med. 2014;371(25):2383-2393.
11. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352(16):1685-1695.
12. Duewell P, Kono H, Rayner KJ, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464(7293):1357-1361.
13. Ridker PM. From C-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ Res. 2016;118(1):145-156.
14. Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science. 2013;339(6116):161-166.
15. Libby P, Nahrendorf M, Swirski FK. Leukocytes link local and systemic inflammation in ischemic cardiovascular disease: an expanded cardiovascular continuum. J Am Coll Cardiol. 2016;67(9):1091-1103.
16. Soehnlein O, Libby P. Targeting inflammation in atherosclerosis — from experimental insights to the clinic. Nat Rev Drug Discov. 2021;20(8):589-610.
17. Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the CDC and the AHA. Circulation. 2003;107(3):499-511.
18. Emerging Risk Factors Collaboration; Kaptoge S, Di Angelantonio E, Lowe G, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375(9709):132-140.
19. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002;347(20):1557-1565.
20. Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207.
21. Ridker PM, MacFadyen JG, Everett BM, et al. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial. Lancet. 2018;391(10118):319-328.
22. Ridker PM, Bhatt DL, Pradhan AD, Glynn RJ, MacFadyen JG, Nissen SE. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials. Lancet. 2023;401(10384):1293-1301.
23. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000;101(15):1767-1772.
24. Kaptoge S, Seshasai SRK, Gao P, et al. Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur Heart J. 2014;35(9):578-589.
25. Ridker PM, Rane M. Interleukin-6 signaling and anti-interleukin-6 therapeutics in cardiovascular disease. Circ Res. 2021;128(11):1728-1746.
26. Fibrinogen Studies Collaboration. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA. 2005;294(14):1799-1809.
27. Brennan ML, Penn MS, Van Lente F, et al. Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med. 2003;349(17):1595-1604.
28. Baldus S, Heeschen C, Meinertz T, et al. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation. 2003;108(12):1440-1445.
29. Latini R, Maggioni AP, Peri G, et al. Prognostic significance of the long pentraxin PTX3 in acute myocardial infarction. Circulation. 2004;110(16):2349-2354.
30. Horne BD, Anderson JL, John JM, et al. Which white blood cell subtypes predict increased cardiovascular risk? J Am Coll Cardiol. 2005;45(10):1638-1643.
31. Núñez J, Núñez E, Bodí V, et al. Usefulness of the neutrophil to lymphocyte ratio in predicting long-term mortality in ST segment elevation myocardial infarction. Am J Cardiol. 2008;101(6):747-752.
32. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Circulation. 2019;139(25):e1082-e1143.
33. Rosenson RS, Brewer HB Jr, Davidson WS, et al. Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation. 2012;125(15):1905-1919.
34. Westerterp M, Bochem AE, Yvan-Charvet L, Murphy AJ, Wang N, Tall AR. ATP-binding cassette transporters, atherosclerosis, and inflammation. Circ Res. 2014;114(1):157-170.
35. Zhu X, Owen JS, Wilson MD, et al. Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol. J Lipid Res. 2010;51(11):3196-3206.
36. Yvan-Charvet L, Pagler T, Gautier EL, et al. ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation. Science. 2010;328(5986):1689-1693.
37. Murphy AJ, Akhtari M, Tolani S, et al. ApoE regulates hematopoietic stem cell proliferation, monocytosis, and monocyte accumulation in atherosclerotic lesions in mice. J Clin Invest. 2011;121(10):4138-4149.
38. Murphy AJ, Woollard KJ, Hoang A, et al. High-density lipoprotein reduces the human monocyte inflammatory response. Arterioscler Thromb Vasc Biol. 2008;28(11):2071-2077.
39. Mauldin JP, Nagelin MH, Wojcik AJ, et al. Reduced expression of ATP-binding cassette transporter G1 increases cholesterol accumulation in macrophages of patients with type 2 diabetes mellitus. Circulation. 2008;117(21):2785-2792.
40. 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.
41. Ebtehaj S, Gruppen EG, Bakker SJL, Dullaart RPF, Tietge UJF. HDL (high-density lipoprotein) cholesterol efflux capacity is associated with incident cardiovascular disease in the general population. Arterioscler Thromb Vasc Biol. 2019;39(9):1874-1883.
42. Feingold KR, Grunfeld C. Effect of inflammation on HDL structure and function. Curr Opin Lipidol. 2016;27(5):521-530.
43. Ansell BJ, Navab M, Hama S, et al. Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation. 2003;108(22):2751-2756.
44. McMahon M, Grossman J, FitzGerald J, et al. Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 2006;54(8):2541-2549.
45. Low H, Hoang A, Sviridov D. Cholesterol efflux assay. J Vis Exp. 2012;(61):3810.
46. Sankaranarayanan S, Kellner-Weibel G, de la Llera-Moya M, et al. A sensitive assay for ABCA1-mediated cholesterol efflux using BODIPY-cholesterol. J Lipid Res. 2011;52(12):2332-2340.
47. Rosenson RS, Brewer HB Jr, Ansell BJ, et al. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat Rev Cardiol. 2016;13(1):48-60.
48. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-188.
