Transgenic pigs for cardiovascular disease research

LARIF supports translational cardiovascular research through specialist large animal models, advanced imaging and physiological phenotyping.

Using an inducible transgenic pig model of endothelin-1 (EDN1)-driven cardiovascular disease and fibrosis, researchers can investigate disease mechanisms, progression and emerging therapies in a physiologically relevant model with important similarities to human cardiovascular biology.

Background

Cardiovascular disease remains one of the leading causes of death worldwide. While rodent models have been invaluable for understanding disease mechanisms, important differences in cardiovascular physiology can limit their translation to human patients.

Pigs are increasingly recognised as an important translational species due to their close similarities to humans in heart size, cardiovascular anatomy, vascular biology, immune function, and physiology. To help bridge the gap between laboratory discovery and clinical application, we have developed a novel transgenic pig model carrying additional copies of the EDN1 gene under the control of an inducible promoter. This work builds upon The Roslin Institute’s international reputation for large animal transgenesis

EDN1 encodes endothelin-1, a potent vasoconstrictor associated with hypertension, vascular dysfunction, and tissue fibrosis. The inducible system allows researchers to activate the transgene in adult animals through dietary administration of doxycycline, enabling controlled investigation of disease development and progression.

At LARIF

The LARIF provided specialist infrastructure and expertise throughout the development and characterisation of the model.

Key capabilities included:

  • embryo manipulation and transgenesis facilities for generation of the founder transgenic animals
  • 3T MR imaging for detailed assessment of cardiac and neurological changes following transgene activation
  • specialist animal accommodation supporting controlled administration of doxycycline
  • physiological monitoring facilities enabling repeated, non-invasive blood pressure measurements in conscious animals.

By integrating advanced imaging, physiological phenotyping, and large animal transgenesis within a single research environment, the LARIF enabled comprehensive longitudinal evaluation of this novel cardiovascular disease model.

Impact

This programme established a unique large animal platform for investigating the role of endothelin-1 in cardiovascular disease and fibrosis. The model provides opportunities to study disease mechanisms in a physiologically relevant species and to evaluate emerging therapeutic interventions in a setting that more closely reflects human disease.

The scientific value of the programme has been recognised through continued funding from the British Heart Foundation, supporting ongoing development and characterisation of the model. 

As findings are disseminated, the platform has the potential to accelerate translational cardiovascular research and support future collaborations with academic, clinical, and industry partners.

Publications

Transgenic domestic pigs for research in vascular contributions to cognitive impairment and dementia

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