Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
5-Year IF – 2.0, IF – 1.9, JCI (2024) – 0.43
Scopus CiteScore – 4.3
Q1 in SJR 2024, SJR score – 0.598, H-index: 49 (SJR)
ICV – 161.00; MNiSW – 70 pts
Initial editorial assessment and first decision within 24 h

ISSN 1899–5276 (print), ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2017, vol. 26, nr 4, July, p. 655–659

doi: 10.17219/acem/62836

PubMed ID: 28691419

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Circulating PCSK9 affects serum LDL and cholesterol levels more than SREBP-2 expression

Asghar Mohammadi1,B,C,D, Mohamad Shabani2,A, Faezeh Naseri3,B,F, Bita Hosseni2,B,F, Elham Soltanmohammadi2,B,F, Sadegh Piran2,B,F, Mohammad Najafi2,4,A,C,D,E,F

1 Biochemistry Department, Medical School, Tarbiat Modares University of Medical Sciences, Tehran, Iran

2 Biochemistry Department, Medical School, Iran University of Medical Sciences, Tehran, Iran

3 Biochemistry Department, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Cellular and Molecular Research Center, Biochemistry Department, Medical School, Iran University of Medical Sciences, Tehran, Iran

Abstract

Background. Cholesterol homeostasis is dependent upon the sterol regulatory element binding protein 2 (SREBP-2) regulatory system and the functioning of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9). Many studies have also reported that low density lipoprotein receptor (LDLR) levels in cellular membranes are related to the functioning of these proteins.
Objectives. The aim of this study was to investigate the association of lipid profiles with circulating PCSK9 protein values and SREBP-2 expression levels in normal subjects.
Material and Methods. The study involved 120 randomly chosen healthy subjects. Their lipid profiles were measured using routine laboratory techniques, and the plasma PCSK9 protein and SREBP-2 expression levels were determined by ELISA and real time quantitative PCR methods, respectively. A statistical analysis was carried out using a statistical software package.
Results. Linear regression analyses showed a significant correlation between total cholesterol and PCSK9 (3.54 ± 1.31 ng/mL), as well as between total cholesterol and SREBP-2 (0.1–35.38) (p = 0.002 and p = 0.02, respectively). Furthermore, multiple regression analyses showed strict correlations between PCSK9 and cholesterol-related parameters especially the total cholesterol/HDL-C ratio (β = 3.53, p = 0.001). There was no significant correlation between circulating PCSK9 and SREBP-2 expression levels (r = 1.2, p = 0.3).
Conclusion. The study results revealed that serum cholesterol-related parameters are strictly associated with plasma PCSK9 values, suggesting that PCSK9 function has a greater effect on serum total cholesterol levels than SREBP-2 expression does. Furthermore, the total cholesterol/HDL-C ratio was a better indicator for evaluating PCSK9 level than total cholesterol.

Key words

lipid profile, PCSK9, SREBP-2

References (18)

  1. Thompson RC, Allam AH, Zink A, Wann, et al. Computed tomographic evidence of atherosclerosis in the mummified remains of humans from around the world. Glob Heart. 2014;9(2):187–196.
  2. Gijsberts CM, den Ruijter HM, Asselbergs FW, Chan MY, de Kleijn DP, Hoefer IE. Biomarkers of coronary artery disease differ between Asians and Caucasians in the general population. Glob Heart. 2015; pii: S2211-8160(14)02671-4.
  3. Patel SD, Zymvragoudakis V, Sheehan L, Lea T, Modarai B, Katsanos K,Zayed H. Atherosclerotic Plaque Analysis: A Pilot Study to Assess a Novel Tool to Predict Outcome Following Lower Limb Endovascular Intervention. Eur J Vasc Endovasc Surg. 2015; pii: S1078-5884(15)00326-3.
  4. Najafi M, Roustazadeh A, Alipoor B. Ox-LDL particles: Modified components, cellular uptake, biological roles and clinical assessments. Cardiovasc Hematol Disord Drug Targets. 2011;119–128.
  5. Eberlé D, Hegarty B, Bossard P, Ferré P, Foufelle F. SREBP transcription factors: master regulators of lipid homeostasis. Biochimie. 2004;86(11):839–848.
  6. Shimada YJ, Cannon CP. PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitors: Past, present, and the future. Eur Heart J. 2015; pii: ehv174.
  7. Sokolov A, Radhakrishnan A. Accessibility of cholesterol in endoplasmic reticulum membranes and activation of SREBP-2 switch abruptly at a common cholesterol threshold. J Biol Chem. 2010;285(38):29480–29490.
  8. Strøm TB, Tveten K, Leren TP. PCSK9 acts as a chaperone for the LDL receptor in the endoplasmic reticulum. Biochem J. 2014;457(1): 99-105.
  9. Jeong HJ, Lee HS, Kim KS, Kim YK, Yoon D, Park SW. Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2. J Lipid Res. 2008;49(2):399–409.
  10. Schulz R, Schlüter KD, Laufs U. Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9). Basic Res Cardiol. 2015;110(2):4.
  11. Mbikay M, Mayne J, Chrétien M. Proprotein convertases subtilisin/kexin type 9, an enzyme turned escort protein: hepatic and extra hepatic functions. J Diabetes. 2013;5(4):391–405.
  12. Alborn WE, Cao G, Careskey HE, Qian YW, et al. Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum LDL cholesterol. Clin Chem. 2007;53(10):1814–1819.
  13. Lambert G, Ancellin N, Charlton F, et al. Plasma PCSK9 concentrations correlate with LDL and total cholesterol in diabetic patients and are decreased by fenofibrate treatment. Clin Chem. 2008;54(6):1038–1045.
  14. Cariou B, Si-Tayeb K, Le May C. Role of PCSK9 beyond liver involvement. Curr Opin Lipidol. 2015;26(3):155–161.
  15. Mbikay M, Sirois F, Simoes S, Mayne J, Chrétien M. Quercetin-3-glucoside increases low-density lipoprotein receptor (LDLR) expression, attenuates proprotein convertase subtilisin/kexin 9 (PCSK9) secretion, and stimulates LDL uptake by Huh7 human hepatocytes in culture. FEBS Open Bio. 2014;4:755–762.
  16. Shin DJ, Osborne TF. Thyroid hormone regulation and cholesterol metabolism are connected through Sterol Regulatory Element-Binding Protein-2 (SREBP-2). J Biol Chem. 2003;278(36):34114–34118.
  17. Dong B, Wu M, Li H, Kraemer FB, Adeli K, Seidah NG, Park SW, Liu J.Strong induction of PCSK9 gene expression through HNF1alpha and SREBP2: mechanism for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic hamsters. J Lipid Res. 2010;51(6):1486–1495.
  18. Wang L, Xu F, Zhang XJ, Jin RM, Li X. Effect of high-fat diet on cholesterol metabolism in rats and its association with Na(+)/K (+)-ATPase/Src/pERK signaling pathway. J Huazhong Univ Sci Technolog Med Sci. 2015;35(4):490–494.
© Wroclaw Medical University