Transcriptional down-regulation of the platelet ADP receptor P2Y(12) and clusterin in patients with systemic lupus erythematosus

J Thromb Haemost. 2004 Aug;2(8):1436-42. doi: 10.1111/j.1538-7836.2004.00854.x.

Abstract

Cardiovascular complications are common in systemic lupus erythematosus (SLE) and myocardial infarctions are the leading cause of increased mortality. The ADP receptor P2Y(12) plays a central role in platelet activation and the P2Y(12) blocker clopidogrel reduces the incidence of cardiovascular events. Clusterin, a complement inhibitory protein suggested to be involved in the pathogenesis of SLE, has been found recently in a microarray study to be expressed at very high levels in platelets. Using a new protocol for mRNA quantification in platelets we set out to study if gene expression is altered in SLE patients compared with a healthy control group. Quantitative assay based on real-time PCR was used to measure mRNA expression, Western blot for P2 receptor protein expression and PFA-100 for platelet aggregation. The P2Y(12) receptor expression was decreased in SLE compared to the controls (P < 0.05), while expression of P2Y(1) and P2X(1) were unaltered. These findings were consistent at the protein level. The clusterin mRNA expression was very high. However, SLE patients had significantly lower levels than controls (P < 0.05). Platelet aggregation was similar in both groups. It may be suggested that a decreased level of P2Y(12) receptors could represent a protective response in SLE against thrombotic complications. Lowered clusterin levels could be involved in the pathogenesis of SLE due to decreased protective effects. These findings could help to achieve a better understanding of the platelet function in SLE and serve as a guide for further research and drug use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Platelets / metabolism
  • Blotting, Western
  • Clopidogrel
  • Clusterin
  • Dimerization
  • Down-Regulation*
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Glycoproteins / biosynthesis*
  • Glycoproteins / genetics*
  • Humans
  • Linear Models
  • Lupus Erythematosus, Systemic / metabolism*
  • Male
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics*
  • Middle Aged
  • Molecular Chaperones / biosynthesis*
  • Molecular Chaperones / genetics*
  • Platelet Activation
  • Platelet Aggregation
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Purinergic P2 / biosynthesis*
  • Receptors, Purinergic P2 / genetics*
  • Receptors, Purinergic P2Y12
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology

Substances

  • CLU protein, human
  • Clusterin
  • Glycoproteins
  • Membrane Proteins
  • Molecular Chaperones
  • P2RY12 protein, human
  • RNA, Messenger
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y12
  • RNA
  • Clopidogrel
  • Ticlopidine