Investigating the Effect of a Single Infusion of Reconstituted High-Density Lipoprotein in Patients with Symptomatic Carotid Plaques

Ann Vasc Surg. 2015 Oct;29(7):1380-91. doi: 10.1016/j.avsg.2015.04.084. Epub 2015 Jun 30.

Abstract

Background: Elevation of plasma high-density lipoprotein (HDL) cholesterol concentration reduces cardiovascular mortality and morbidity. HDLs have been shown to possess acute anti-inflammatory, antioxidant, and antithrombotic properties. We hypothesize that HDL therapy can acutely alter local and systemic manifestations of plaque instability.

Methods: Forty patients with early symptomatic carotid disease were randomized to either receive reconstituted HDL (rHDL) 40 mg/kg (n = 20) or placebo (n = 20). Carotid endarterectomies were performed 24 hr later. Plaques were obtained intraoperatively and used for measurement of thrombomodulatory genes expression. Plasma samples were collected before the infusion, 24 and 48 hr later to measure changes in systemic markers of plaque instability.

Results: No significant differences were noted in thrombomodulatory genes expression between the 2 groups. Systemic levels of tissue factor, matrix metalloproteinase 9 (MMP-9), and monocyte chemotactic factor-1 (MCP-1) were significantly reduced in the rHDL group. However, the effects on MMP-9 and MCP-1 were abolished in the immediate postoperative period. Although rHDL did not affect plasma interleukin-6 levels 24 hr following the infusion, it prevented the significant postoperative elevation seen in the placebo group.

Conclusions: A single infusion of rHDL can acutely alter plasma biomarkers associated with plaque instability and cardiovascular morbidity.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Carotid Artery, Internal / metabolism
  • Carotid Artery, Internal / pathology
  • Carotid Artery, Internal / surgery*
  • Carotid Stenosis / blood
  • Carotid Stenosis / complications
  • Carotid Stenosis / diagnosis
  • Carotid Stenosis / genetics
  • Carotid Stenosis / therapy*
  • Endarterectomy, Carotid*
  • Female
  • Gene Expression Regulation
  • Humans
  • Inflammation Mediators / blood
  • Infusions, Intravenous
  • Lipoproteins, HDL / administration & dosage*
  • Lipoproteins, HDL / blood
  • London
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic*
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Inflammation Mediators
  • Lipoproteins, HDL