PCSK9: регуляция биологической активности и связь с обменом жиров и углеводов

PCSK9: регуляция биологической активности и связь с обменом жиров и углеводов

Автор: Аверкова Анастасия Олеговна

Журнал: Клиническая практика @clinpractice

Рубрика: Обзоры

Статья в выпуске: 3 (31), 2017 года.

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Пропротеиновая конвертаза субтилизин-кексинового типа 9 (PCSK9) - сериновая протеаза, участвующая в регуляции экспрессии рецепторов липопротеидов низкой плотности (ЛПНПР) и метаболизме apoB липопротеидов. Известно, что экспрессия PCSK9 в печени, а также её активность и секреция оказывают значительное влияние на обмен холестерина. Повышение уровня печеночной PCSK9 ведет к усиленному разрушению ЛПНПР, что приводит к снижению захвата apoB липопротеинов и последующему увеличению концентрации в плазме липопротеидов, включая ЛПНП. В результате PCSK9 стала новой мишенью липид-снижающих препаратов. Целью обзора является освещение текущих сведений о метаболической и связанной с питанием регуляции PCSK9 и влиянии на уровень холестерина, обмен apoB липопротеидов и риск сердечно-сосудистых заболеваний (ССЗ).

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Гиперлипидемия, лпнп

Короткий адрес: https://sciup.org/143164652

IDR: 143164652

Список литературы PCSK9: регуляция биологической активности и связь с обменом жиров и углеводов

  • Shimada Y.J., Cannon C.P. PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitors: past, present, and the future. European Heart Journal 2015; 36(36):2415-2424.
  • Dron J.S., Hegele R.A. Complexity of mechanisms among human proprotein convertase subtilisin-kexin type 9 variants. Current opinion in lipidology 2017; 28(2):161-169.
  • Ito M.K., Santos R.D. PCSK9 Inhibition With Monoclonal Antibodies: Modern Management of Hypercholesterolemia. J Clin Pharmacol 2017; 57(1):7-32.
  • Cariou B., Le May C., Costet P. Clinical aspects of PCSK9. Atherosclerosis 2011; 216(2):258-265.
  • Browning J.D., Horton J.D. Fasting reduces plasma proprotein convertase, subtilisin/kexin type 9 and cholesterol biosynthesis in humans. Journal of Lipid Research 2010; 51(11):3359-3363.
  • Guo Y.L., Zhang W., Li J.J. PCSK9 and lipid lowering drugs. Clinica chimica acta; international journal of clinical chemistry 2014; 437:66-71.
  • Horton J.D., Shah N.A., Warrington J.A. et al. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proceedings of the National Academy of Sciences of the United States of America 2003; 100(21):12027-12032.
  • Hua X., Yokoyama C., Wu J. et al. SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proceedings of the National Academy of Sciences of the United States of America 1993; 90(24):11603-11607.
  • Maxwell K.N., Soccio R.E., Duncan E.M. et al. Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice. Journal of Lipid Research 2003; 44(11):2109-2119.
  • Careskey H.E., Davis R.A., Alborn W.E. et al. Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9. Journal of Lipid Research 2008, 49(2):394-398.
  • Horton J.D., Cohen J.C., Hobbs H.H. Molecular biology of PCSK9: its role in LDL metabolism. Trends in biochemical sciences 2007; 32(2):71-77.
  • Abifadel M., Varret M., Rabes J.P. et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nature genetics 2003; 34(2):154-156.
  • Tavori H., Fan D., Blakemore J.L. et al. Serum proprotein convertase subtilisin/kexin type 9 and cell surface low-density lipoprotein receptor: evidence for a reciprocal regulation. Circulation 2013; 127(24):2403-2413.
  • Timms K.M., Wagner S., Samuels M.E. et al. A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree. Hum Genet 2004; 114(4):349-353.
  • Kosenko T., Golder M., Leblond G. etal. Lowdensity lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation. J Biol Chem 2013; 288(12):8279-8288.
  • Tavori H., Giunzioni I., Linton M.R.F. et al. Loss of Plasma Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) After Lipoprotein Apheresis. Circulation research 2013; 113(12):1290-1295.
  • Benjannet S., Rhainds D., Hamelin J. et al. The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications. J Biol Chem 2006; 281(41):30561-30572.
  • Han B., Eacho P.I., Knierman M.D. et al. Isolation and characterization of the circulating truncated form of PCSK9. Journal of Lipid Research 2014; 55(7):1505-1514.
  • Lipari M.T., Li W., Moran P. et al. Furin-cleaved proprotein convertase subtilisin/kexin type 9 (PCSK9) is active and modulates low density lipoprotein receptor and serum cholesterol levels. J Biol Chem 2012; 287(52):43482-43491.
  • Kraemer F.B., Laane C., Park B. et al. Low-density lipoprotein receptors in rat adipocytes: regulation with fasting. The American journal of physiology 1994; 266(1 Pt 1):E26-32.
  • Nishikawa S., Doi K., Nakayama H. et al. The effect of fasting on hepatic lipid accumulation and transcriptional regulation of lipid metabolism differs between C57BL/6J and BALB/cA mice fed a high-fat diet. Toxicologic pathology 2008; 36(6):850-857.
  • Persson L., Cao G., Stahle L. et al. Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans. Arterioscler Thromb Vasc Biol 2010; 30(12):2666-2672.
  • Baass A., Dubuc G., Tremblay M. et al. Plasma PCSK9 isassociatedwithage, sex, andmultiplemetabolic markers in a population-based sample of children and adolescents. Clinical chemistry 2009; 55(9):1637-1645.
  • Dubuc G., Tremblay M., Pare G. et al. A new method for measurement of total plasma PCSK9: clinical applications. Journal of Lipid Research 2010; 51(1):140-149.
  • Lakoski S.G., Lagace T.A., Cohen J.C. et al. Genetic and metabolic determinants of plasma PCSK9 levels. The Journal of clinical endocrinology and metabolism 2009; 94(7):2537-2543.
  • Persson L., Gälman C., Angelin B. et al. Importance of Proprotein Convertase Subtilisin/Kexin Type 9 in the Hormonal and Dietary Regulation of Rat Liver Low-Density Lipoprotein Receptors. Endocrinology 2009; 150(3):1140-1146.
  • Wu M., Dong B., Cao A. et al. Delineation of molecular pathways that regulate hepatic PCSK9 and LDL receptor expression during fasting in normolipidemic hamsters. Atherosclerosis 2012; 224(2):401-410.
  • Li H., Dong B., Park S.W. et al. Hepatocyte nuclear factor 1alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine. J Biol Chem 2009; 284(42):28885-28895.
  • Ricoult S.J., Manning B.D. The multifaceted role of mTORC1 in the control of lipid metabolism. EMBO reports 2013; 14(3):242-251.
  • Kourimate S., Le May C., Langhi C. et al. Dual mechanisms for the fibrate-mediated repression of proprotein convertase subtilisin/kexin type 9. J Biol Chem 2008; 283(15):9666-9673.
  • Costet P., Cariou B., Lambert G. et al. Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c. J Biol Chem 2006; 281(10):6211-6218.
  • Langhi C., Le May C., Gmyr V. et al. PCSK9 is expressed in pancreatic delta-cells and does not alter insulin secretion. Biochem Biophys Res Commun 2009; 390(4):1288-1293.
  • Mbikay M., Sirois F., Mayne J. et al. PCSK9-deficient mice exhibit impaired glucose tolerance and pancreatic islet abnormalities. FEBS letters 2010; 584(4):701-706.
  • Bonnefond A., Yengo L., Le May C. et al. The loss-of-function PCSK9 p.R46L genetic variant does not alter glucose homeostasis. Diabetologia 2015; 58(9):2051-2055.
  • Roth E.M., Taskinen M.R., Ginsberg H.N. et al. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial. Int J Cardiol 2014; 176(1):55-61.
  • Cariou B., Langhi C., Le Bras M. et al. Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets. Nutrition & Metabolism 2013; 10(1):4.
  • Li Y., Xu S., Mihaylova M.M. et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell metabolism 2011; 13(4):376-388.
  • Bjermo H., Iggman D., Kullberg J. et al. Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. The American journal of clinical nutrition 2012; 95(5):1003-1012.
  • Richard C., Couture P., Desroches S. et al. Effect of the Mediterranean diet with and without weight loss on surrogate markers of cholesterol homeostasis in men with the metabolic syndrome. The British journal of nutrition 2012; 107(5):705-711.
  • Galland L. Diet and Inflammation. Nutrition in Clinical Practice 2010; 25(6):634-640.
  • Sekiya M., Yahagi N., Matsuzaka T. et al. Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology 2003; 38(6):1529-1539.
  • Jänis M.T., Tarasov K., Ta H.X. et al. Beyond LDL-C lowering: Distinct molecular sphingolipids are good indicators of proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency. Atherosclerosis 2013; 228(2):380-385.
  • Dong B., Singh A.B., Azhar S. et al. High-fructose feeding promotes accelerated degradation of hepatic LDL receptor and hypercholesterolemia in hamsters via elevated circulating PCSK9 levels. Atherosclerosis 2015; 239(2):364-374.
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