ASSOCIATION OF PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 WITH HYPERTENSION AND SMOKING
K. S. Benimetskaya,
M. P. Yachmeneva,
S. V. Astrakov,
L. V. Shcherbakova,
D. V. Denisova,
Yu. I. Ragino,
M. I. Voevoda 
Abstract
Objectives. To estimate the relationship of proprotein convertase subtilisin/kexin type 9 (PCSK9) level with blood pressure (BP) and smoking in a population of young males in Novosibirsk.
Material and methods. The group was formed by the method of random numbers from the population sample of Novosibirsk that underwent a one-time survey as part of the screening «Monitoring of health status and prevalence of risk factors of therapeutic diseases, their prediction and prevention in Siberia». The study included 492 males, the average age was 36.0 ± 5.86 years. Levels of PCSK9 were determined with ELISA using a test system «Human PCSK9 ELISA» (BioVendor, Czech Republic).
Results. The average level of the PCSK9 protein was 325.9 ± 141.97 ng/ml, median (interquartile range) was 300.19 (240.20; 361.80). Mean systolic BP was 126.13 ± 13.40 mm Hg, mean diastolic BP was 82.91 ± 9.93 mm Hg. Fifety-six percent (277 males) was non-smokers, 44% (214 males) smoked. PCSK9 levels were higher in sample of smokers (339.49 ± 139.86; 311.82 (251.04; 369.78)) than in sample of non-smokers (315.17 ± 143.16; 286.16 (229.91; 351.71)) (p = 0.011), samples were independent. There was no difference in the level of PCSK9 protein in a pair of samples contrasting in BP. A weak statistically significant correlation between the level of PCSK9 and smoking (rs = 0.115, p = 0.01) was shown, it was indirectly confirmed by the result of multiple regression analysis. Hypertension was an independent predictor of higher levels of PCSK9 protein according to multivariate linear regression analysis using a stepwise method (B = 32.593; SE = 14.624; p = 0.026). Also hypertension was an independent predictor of a higher level of PCSK9 protein according to multivariate linear regression analysis using the backward method in the same model (B = 30.457; SE = 14.649; p = 0.038).
Conclusion. The presence of hypertension indicates an increased level of PCSK9. The obtained data support the role of PCSK9 in the pathogenesis of cardiovascular diseases and the prospect of its use as a biological marker. Present study was the first one of such category in Russia.
Supporting agencies: RFBR according to the research project № 18-34-00763
About the Authors
K. S. Benimetskaya
Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
Junior research assistant, laboratory for clinical biochemical and hormonal researches of therapeutic diseases, IIPM – Branch of IC&G SB RAS, teaching assistant of general medicine faculty, Novosibirsk National Research University
175/1, B. Bogatkova str., Novosibirsk, 630089
M. P. Yachmeneva
Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Medical resident, IIPM – Branch of IC&G SB RAS, laboratory for clinical biochemical and hormonal researches of therapeutic diseases
Russian Federation
Medical resident, IIPM – Branch of IC&G SB RAS, laboratory for clinical biochemical and hormonal researches of therapeutic diseases
S. V. Astrakov
Novosibirsk State University
Russian Federation
Dr. of Sci. (Med.), professor, Institute of Medicine and Psychology
Russian Federation
Dr. of Sci. (Med.), professor, Institute of Medicine and Psychology
L. V. Shcherbakova
Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Senior research assistant, laboratory of clinical population and preventive researches of therapeutic and hormonal diseases
Russian Federation
Senior research assistant, laboratory of clinical population and preventive researches of therapeutic and hormonal diseases
D. V. Denisova
Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Dr. of Sci. (Med.), leading research assistant, laboratory of preventive medicine
Russian Federation
Dr. of Sci. (Med.), leading research assistant, laboratory of preventive medicine
Yu. I. Ragino
Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Dr. of Sci. (Med.), professor of RAS, corresponding member of RAS, head of laboratory for clinical biochemical and hormonal researches of therapeutic diseases, Deputy Director for Science
Russian Federation
Dr. of Sci. (Med.), professor of RAS, corresponding member of RAS, head of laboratory for clinical biochemical and hormonal researches of therapeutic diseases, Deputy Director for Science
M. I. Voevoda
Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Dr. of Sci. (Med.), professor, academician of RAS, head of IIPM – Branch of IC&G SB RAS
Russian Federation
Dr. of Sci. (Med.), professor, academician of RAS, head of IIPM – Branch of IC&G SB RAS
References
1. Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derré A, Villéger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, Boileau C. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34:154-156.
2. Cohen JC, Boerwinkle E, Mosley Jr TH, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354(12):1264-72.
3. Park SW, Moon Y-A, Horton JD. Posttranscriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/ kexin type 9a in mouse liver. J Biol Chem. 2004;279(48): 50630-8.
4. Sabatine MS, Giugliano RP, KeechAC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017;376(18):1713-22.
5. Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Lecorps G, Mahaffey KW, Moryusef A, Pordy R, Quintero K, Roe MT, Sasiela WJ, Tamby JF, Tricoci P, White HD, Zeiher AM. ODYSSEY OUTCOMES Committees and Investigators (2018) Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379:2097-2107.
6. Mbikay M, Sirois F, Mayne J et al. PCSK9deficient mice exhibit impaired glucose tolerance and pancreatic islet abnormalities. FEBS Lett. 2010;584(4):701-6.
7. Lakoski SG, Lagace TA, Cohen JC, Horton JD, Hobbs HH. Genetic and metabolic determinants of plasma PCSK9 levels. J Clin Endocrinol Metab. 2009;94(7):2537-43.
8. Hachem А, Hariri E, Saoud P, Lteif C, Lteif L, Welty F. The Role of Proprotein Convertase Subtilisin/ Kexin Type 9 (PCSK9) in Cardiovascular Homeostasis: A Non-Systematic Literature Review. Current Cardiology Reviews. 2017;13:274-282.
9. Leander K., Mälarstig A., Van’t Hooft F.M. et al. Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Predicts Future Risk of Cardiovascular Events Independently of Established Risk Factors. Circulation. 2016;133(13):1230-9.
10. Sharotri V, Collier DM, Olson DR, Zhou R, Snyder PM. Regulation of epithelial sodium channel trafficking by proprotein convertase subtilisin/kexin type 9 (PCSK9). J Biol Chem. 2012; 287(23):19266-74.
11. Bhalla V, Hallows KR. Mechanisms of ENaC regulation and clinical implications. J Am Soc Nephrol. 2008;19(10):1845-54.
12. Kleyman TR, Carattino MD, Hughey RP. ENaC at the cutting edge: regulation of epithelial sodium channels by proteases. J Biol Chem. 2009;284(31):20447-51.
13. Hachem A, Hariri E, Saoud P, Lteif C, Lteif L, Welty F. The Role of Proprotein Convertase Subtilisin/ Kexin Type 9 (PCSK9) in Cardiovascular Homeostasis: A Non-Systematic Literature Review. Curr Cardiol Rev. 2017;13(4):274-282.
14. Cariou B, Le May C, Costet P. Clinical aspects of PCSK9. Atherosclerosis. 2011;216:258–265.
15. Cui Q, Ju X, Yang T, Zhang M, Tang W, Chen Q, Hu Y, Haas JV, Troutt JS, Pickard RT, Darling R, Konrad RJ, Zhou H, Cao G. Serum PCSK9 is associated with multiple metabolic factors in a large Han Chinese population. Atherosclerosis. 2010;213(2):632-636.
16. Chernogubova E, Strawbridge R, Mahdessian H, Mälarstig A, Krapivner S, Gigante B, Hellénius ML, de Faire U, Franco-Cereceda A, Syvänen AC, Troutt JS, Konrad RJ, Eriksson P, Hamsten A, van‘t Hooft FM. Common and low-frequency genetic variants in the PCSK9 locus influence circulating PCSK9 levels. Arterioscler Thromb Vasc Biol. 2012:32(6):15261534.
17. Ridker PM, Rifai N, Bradwin G et al. Plasma proprotein convertase subtilisin/kexin type 9 levels and the risk of first cardiovascular events. Eur Heart J. 2016;37(6):554-60.
18. Ragino YuI, Astrakova KS, Shakhtshneider E, Stakhneva EM, Gafarov VV, Bogatyrev SN, Voevoda MI. Blood Levels of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Men from Different Population Groups and Its Relation to Unfavorable Long-Term Prognosis. Kardiologiia. 2017;4:72-76 (In Russ.).
19. Tran NT, Aslibekyan S, Tiwari HK, Zhi D, Sung YJ, Hunt SC, Rao DC, Broeckel U, Judd SE, Muntner P, Kent ST, Arnett DK, Irvin MR. PCSK9 variation and association with blood pressure in African Americans: preliminary findings from the HyperGEN and REGARDS studies. Front Genet. 2015;6:136.
Review
For citations:
Benimetskaya K.S., Yachmeneva M.P., Astrakov S.V., Shcherbakova L.V., Denisova D.V., Ragino Yu.I., Voevoda M.I. ASSOCIATION OF PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 WITH HYPERTENSION AND SMOKING. Innovative Medicine of Kuban. 2019;(1):20-27. (In Russ.)
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