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Mouse Model of Alloimmune-induced Vascular Rejection and Transplant Arteriosclerosis
07:05

Mouse Model of Alloimmune-induced Vascular Rejection and Transplant Arteriosclerosis

Published on: May 17, 2015

Genetic variants of the hemostatic system and development of transplant coronary artery disease

Jian-Qing He1, Lakshmi K Gaur, April Stempien-Otero

  • 1Puget Sound Blood Center, Seattle, Washington, USA.

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
|June 12, 2002
PubMed

Insights

Donor genetic factors, specifically PAI-1 4G/5G and alpha(2) integrin C807T polymorphisms, predict coronary artery disease (CAD) after heart transplantation. Recipient factors may modify this risk, highlighting local vascular responses in transplant CAD.

Area of Science:

  • Cardiology
  • Transplantation Immunology
  • Genetics

Background:

  • Coronary artery disease (CAD) post-heart transplant may stem from accelerated inflammation and thrombosis.
  • Genetic factors influencing hemostasis and cell adhesion are linked to native CAD.
  • Heart transplantation allows study of recipient vs. donor hemostatic contributions to CAD.

Purpose of the Study:

  • To investigate the role of recipient and donor hemostatic genetic polymorphisms in the development of transplant-associated CAD.
  • To determine if specific genetic variations in hemostasis proteins influence CAD risk after heart transplantation.

Main Methods:

  • Genotyping of hemostatic polymorphisms in 53 heart transplant recipients and their donors.
  • Longitudinal follow-up (average 43 months) with coronary angiography to assess transplant CAD.
  • Analysis of donor and recipient genetic factors in relation to CAD development.

Main Results:

  • Recipient genotype did not predict transplant CAD.
  • Donor polymorphisms in PAI-1 4G/5G and alpha(2) integrin C807T were significant predictors of transplant CAD.
  • Donor PAI-1 4G/4G increased CAD risk (RR 2.6), modified by recipient factors; donor alpha(2) integrin 807 T/T showed higher risk (RR 7.4).

Conclusions:

  • Both donor and recipient genetic and metabolic factors interact at the vessel wall to influence transplant-associated CAD.
  • Findings support the importance of local thrombotic responses to endothelial injury in transplant CAD pathogenesis.
  • Donor-derived genetic predispositions play a crucial role in the development of CAD after heart transplantation.
Abstract

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