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Related Experiment Videos

Endothelial function in pigs transgenic for human complement regulating factor.

Gregor Warnecke1, Sandra R Severson, Mustafa M Ugurlu

  • 1Division of Cardiothoracic Surgery and Transplantation, Department of Surgery, Mayo Clinic and Foundation, 200 First Street SW, Rochester MN 55905, USA.

Transplantation
|April 20, 2002
PubMed
Summary
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Expression of human CD46 in pigs enhances blood vessel relaxation, potentially improving xenotransplantation outcomes. This study investigated endothelial function in transgenic pigs, finding increased relaxation responses to bradykinin.

Area of Science:

  • Transplantation immunology
  • Vascular biology
  • Xenotransplantation

Background:

  • Porcine organs expressing human complement regulating factor (hCRF) resist hyperacute rejection in xenotransplantation.
  • This study investigates endothelial and smooth muscle function in arteries of pigs genetically modified to express human CD46 (hCD46).

Purpose of the Study:

  • To characterize the endothelial and smooth muscle function of arteries from pigs expressing hCD46.
  • To assess the impact of hCD46 expression on vascular reactivity and key vasoactive substances.

Main Methods:

  • Analysis of plasma for angiotensin-converting enzyme (ACE), C-type natriuretic peptide (CNP), and nitric oxide in hCD46 transgenic and nontransgenic pigs.
  • Measurement of nitric oxide synthase (NOS) mRNA and activity in aortic endothelial cells.

Related Experiment Videos

  • Isometric tension measurements in isolated femoral and pulmonary artery rings.

    • Main Results:

    • Transgenic pigs showed significantly higher CNP levels and lower nitric oxide levels compared to controls.
    • Endothelium-dependent relaxations to bradykinin and acetylcholine were enhanced in arteries from hCD46 transgenic pigs.
    • No significant differences in ACE or NOS activity were observed between groups.

    Conclusions:

    • hCD46 expression in porcine endothelium selectively augments endothelium-dependent relaxations, likely via factors other than nitric oxide.
    • ACE and NOS activity remain unchanged by hCD46 expression.
    • Enhanced bradykinin-induced relaxations may reduce vascular resistance, benefiting xenotransplantation outcomes.