Evaluation of plasma PCSK9 concentrations, transcript of LDL receptor, as well as the total number of monocyte LDL receptors in acute coronary syndrome patients

Cardiol J. 2016;23(6):604-609. doi: 10.5603/CJ.a2016.0068. Epub 2016 Sep 26.

Abstract

Background: Before our study, there were no data concerning complex evaluation of: plasma PCSK9 concentrations, transcript LDL receptor (LDLR), as well as the total amount of monocytes' LDLR in acute coronary syndrome (ACS) patients. PCSK9 levels in a few cohort studies were found to correlate with the number of white blood cells (WBC) or platelets (PLT). The study aims to evaluate PCSK9-LDLR concentrations, as well as to find any association between PCSK9 and WBC or PLT.

Methods: The study group included 95 consecutive patients with acute myocardial infarction, in whom angiography/angioplasty of the culprit vessel was performed. The control group consisted of 10 healthy young volunteers. Thirty patients from the studied group were qualified for further percutaneous revascularization after 3 months. Laboratory tests were performed using commercially available kits. LDLR expression on monocyte surface was measured by flow cytometry, but the mRNA level for LDLR was established by real time polymerase chain reaction. The PCSK9 plasma concentration was measured by ELISA kits.

Results: Higher concentration of PCSK9 and amount of LDLR on monocytes surface were observed in patients with ACS compared with healthy young volunteers (number of LDLRs on monocytes [reaction units] 10.8 ± 9.6 vs. 41.8 ± 11.8, p < 0.001, PCSK9 [ng/mL] 295.4 ± 76.4 vs. 213 ± 63.2, p < 0.001). A similar relationship was observed after application of 3-month intensive lipid-lowering therapy in patients with ACS (n = 30, PCSK9 [ng/mL] 281.1 ± 59.5 vs. 358.5 ± 74.7, p < 0.001, LDLR transcript [reaction units] 0.6 ± 0.32 vs. 1.87 ± 0.24, p < 0.001, number of LDLRs on monocytes [reaction units] 5.9 ± 3.1 vs. 22.3 ± 3.8, p < 0.001). There were no significant differences in levels of PCSK9, LDLR between patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). There was no relation of the PCSK9 with WBC as well as with PLT.

Conclusions: We observed significantly higher concentration of PCSK9, and significantly higher levels of mRNA LDLR transcript in patients with ACS compared with healthy young volunteers. A similar pattern was observed after 3 months of intensive statin therapy among patients with ACS. There were no differences in these parameters between patients with STEMI vs. NSTEMI. The results of the study require confirmation in a larger population of patients.

Keywords: LDL receptor; PCSK9; acute coronary syndrome.

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / diagnosis
  • Aged
  • Biomarkers / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Monocytes / metabolism*
  • Proprotein Convertase 9 / blood*
  • RNA / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptors, LDL / blood*
  • Receptors, LDL / genetics
  • Transcription, Genetic

Substances

  • Biomarkers
  • Receptors, LDL
  • RNA
  • PCSK9 protein, human
  • Proprotein Convertase 9