Cardiovascular Revascularization Medicine
Volume 13, Issue 1 , Pages 11-19, January 2012

The role of oxidized phospholipids, lipoprotein (a) and biomarkers of oxidized lipoproteins in chronically occluded coronary arteries in sudden cardiac death and following successful percutaneous revascularization☆

  • Paul Fefer

      Affiliations

    • Schulich Heart Center, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada M4N 3M5
    • Current address: Sheba Medical Center, Tel Aviv University, Tel Aviv.
    • ,
  • Sotirios Tsimikas

      Affiliations

    • Vascular Medicine Program, University of California, San Diego, USA
    • ,
  • Amit Segev

      Affiliations

    • St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
    • Current address: Sheba Medical Center, Tel Aviv University, Tel Aviv.
    • ,
  • John Sparkes

      Affiliations

    • Schulich Heart Center, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada M4N 3M5
    • ,
  • Fumiyuki Otsuma

      Affiliations

    • CVPath Institute, Gaithersburg, MD, USA
    • ,
  • Frank Kolodgie

      Affiliations

    • CVPath Institute, Gaithersburg, MD, USA
    • ,
  • Renu Virmani

      Affiliations

    • CVPath Institute, Gaithersburg, MD, USA
    • ,
  • Joseph Juliano

      Affiliations

    • Vascular Medicine Program, University of California, San Diego, USA
    • ,
  • Thierry Charron

      Affiliations

    • St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
    • Current address: Hôpital du Sacré-Coeur de Montréal, Montréal, Québec.
    • ,
  • Bradley H. Strauss

      Affiliations

    • Schulich Heart Center, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada M4N 3M5
    • Corresponding Author InformationCorresponding author. Schulich Heart Center, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada M4N 3M5. Tel.: +1 416 480 6066; fax: +1 416 480 4745.

Received 17 April 2011; received in revised form 5 August 2011; accepted 15 August 2011. published online 14 November 2011.

Abstract 

Aims

OxPL are pro-inflammatory and may mediate atherogenesis, thrombosis and endothelial dysfunction. We studied the histological presence and temporal increases in oxidized phospholipids on apolipoprotein B-100 particles (OxPL/apoB), lipoprotein (a) [Lp(a)] and biomarkers of oxidized lipoproteins in subjects with chronic total coronary occlusions (CTO) with sudden cardiac death (SCD) and following percutaneous coronary intervention (PCI).

Methods

Eight subjects with SCD and CTO and 33 patients with successful PCI of CTO were included. Blood samples were drawn before PCI, immediately post-PCI, at 6 and 24 h, at 3 days and at 1 week. Plasma levels of OxPL/apoB, Lp(a), IgG and IgM autoantibodies to malondialdehyde (MDA) low-density lipoprotein and apoB-immune complexes were measured in all samples and compared with previous data from 141 patients undergoing PCI of non-CTO vessels.

Results

Immunohistochemistry of coronary CTOs revealed OxPL and MDA-like epitopes, particularly in areas of recanalized and organized thrombus and neovascularization. Following PCI, OxPL/apoB and Lp(a) levels, expressed as percent change from baseline levels before PCI, rose gradually and progressively over the next 7 days. In contrast, levels of OxPL/apoB and Lp(a) in non-CTO vessels rose immediately post PCI and then dropped rapidly to baseline within 24 h.

Conclusions

CTOs contain immunohistological evidence of OxPL and MDA-like epitopes. Successful PCI of CTOs results in a slower increase in OxPL/apoB and Lp(a) but higher increase in IgM immune complexes compared to non-CTO vessels. Pro-inflammatory oxidation-specific epitopes may impact development of CTOs and affect outcomes following PCI that can be evaluated in larger clinical trials.

Keywords: Chronic total occlusion, Oxidized phospholipids, Oxidized LDL, Angioplasty

 

☆ Disclosure: Dr Tsimikas is named as co-inventor of patents and patent applications related to oxidation-specific antibodies, has equity interest in Atherotope, and is a consultant to Quest Diagnostics. The other authors declare no conflicts of interest.

PII: S1553-8389(11)00501-X

doi:10.1016/j.carrev.2011.08.001

Cardiovascular Revascularization Medicine
Volume 13, Issue 1 , Pages 11-19, January 2012

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