Sirolimus Therapy Is Associated with Elevation in Circulating PCSK9 Levels in Cardiac Transplant Patients

Vinaya Simha, Sisi Qin, Pankaj Shah, Byron H. Smith, Walter K. Kremers, Sudhir Kushwaha, Liewei Wang, Naveen L. Pereira

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Sirolimus used in transplantation is often associated with hypercholesterolemia. We measured serum lipid and PCSK9 levels in 51 heart transplant recipients who had their immunosuppressive therapy switched from calcineurin inhibitors to sirolimus. The switch resulted in a 23% increase in LDL cholesterol, and 46% increase in triglycerides and PCSK9 levels increased from 316 ± 105 ng/mL to 343 ± 107 ng/mL (p = 0.04), however the change in PCSK9 levels did not correlate with an increase in lipid levels (p = 0.2). To investigate the mechanism for the variability in the change in PCSK9 levels, lymphoblastoid cell lines were incubated with both sirolimus and everolimus, resulting in a 2–3 fold increase in PCSK9 expression and protein levels in mTOR inhibitor sensitive but not in mTOR inhibitor resistant cell lines. This first in human study demonstrates that sirolimus therapy is associated with elevation in PCSK9 levels which is not associated with sirolimus-induced hypercholesterolemia.

Original languageEnglish (US)
Pages (from-to)9-15
Number of pages7
JournalJournal of cardiovascular translational research
Volume10
Issue number1
DOIs
StatePublished - Feb 1 2017

Keywords

  • Cardiac transplant
  • Hypercholesterolemia
  • PCSK9
  • Sirolimus
  • mTOR inhibitors

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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