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Experimental animal models of coronary microvascular dysfunction.

Oana Sorop1, Jens van de Wouw1, Selena Chandler2

  • 1Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.

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Summary

Animal models of coronary microvascular dysfunction (CMD), a key feature of ischaemia and no obstructive coronary artery disease (INOCA), are crucial for understanding disease mechanisms and testing new therapies for heart disease.

Keywords:
Animal modelCoronary microvascular dysfunctionEndothelial dysfunctionINOCAMetabolic derangements

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Area of Science:

  • Cardiovascular Research
  • Translational Medicine
  • Animal Models of Disease

Background:

  • Coronary microvascular dysfunction (CMD) contributes to myocardial ischaemia, particularly in ischaemia and no obstructive coronary artery disease (INOCA).
  • Effective treatments for INOCA are currently lacking, highlighting the need for better research models.
  • Animal models of CMD are essential for studying INOCA pathophysiology and developing therapeutic strategies.

Purpose of the Study:

  • To provide an overview of existing experimental animal models for coronary microvascular dysfunction (CMD).
  • To focus on models incorporating metabolic derangements as risk factors for CMD.
  • To evaluate the utility of these models for investigating INOCA and related conditions.

Main Methods:

  • Review of animal models of CMD in dogs, swine, rabbits, rats, and mice.
  • Emphasis on models induced by metabolic derangements, including high-fat diets and diabetes (alloxan/streptozotocin).
  • Inclusion of spontaneous and transgenic models exhibiting metabolic derangements.

Main Results:

  • Various animal models successfully replicate metabolic derangements linked to cardiovascular risk.
  • These models exhibit coronary microvascular functional and structural changes comparable to human INOCA.
  • Model outcomes vary based on the type, severity, and duration of risk factor exposure.

Conclusions:

  • Available animal models of CMD are valuable tools for advancing the understanding of INOCA.
  • These models are instrumental in identifying novel therapeutic targets for ischaemic heart disease.
  • They facilitate the development and testing of new interventions to treat heart conditions.