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A diastolic dysfunction model in non-human primates with transverse aortic constriction.

Nicole Zhen1, Sze-Jie Loo1, Li-Ping Su1

  • 1National Heart Research Institute Singapore, National Heart Centre Singapore, 5 Hospital Drive, 169609, Singapore.

Experimental Animals
|June 17, 2021
PubMed
Summary

Transverse aortic constriction (TAC) in non-human primates (NHPs) successfully models cardiac hypertrophy and diastolic dysfunction. This preclinical model shows potential for studying heart conditions and testing therapies.

Keywords:
diastolic dysfunctionfibrosishypertrophytransverse aortic constriction

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Area of Science:

  • Cardiovascular Research
  • Preclinical Animal Models
  • Cardiac Physiology

Background:

  • Transverse aortic constriction (TAC) is a common method for inducing cardiac hypertrophy and heart failure in rodents.
  • Non-human primates (NHPs) offer physiological and anatomical similarities to humans, making them valuable for preclinical disease modeling.
  • Limited studies have explored TAC models in non-human primates.

Purpose of the Study:

  • To establish a transverse aortic constriction (TAC) model in non-human primates (NHPs).
  • To characterize the cardiac structural and functional changes following TAC in NHPs.
  • To evaluate the utility of NHPs as a preclinical model for cardiac diseases.

Main Methods:

  • Surgical placement of a non-absorbable suture around the aorta to create TAC.
  • Division of NHPs into Mild (PG=31.01 ± 12.40 mmHg) and Moderate (PG=53.00 ± 9.37 mmHg) TAC groups.
  • Assessment of cardiac structure and function at 4 weeks post-TAC.

Main Results:

  • Both Mild and Moderate TAC groups exhibited cardiac hypertrophy, including myocyte enlargement and increased left ventricular (LV) wall thickness.
  • Systolic function remained normal in all TAC groups compared to the Sham Group.
  • The Moderate TAC group demonstrated diastolic dysfunction, characterized by altered wave velocities and shortened isovolumic relaxation time, alongside increased cardiac fibrosis.
  • No left ventricular (LV) arrhythmias were observed in TAC groups.

Conclusions:

  • A successful TAC model was established in NHPs, inducing cardiac hypertrophy and diastolic dysfunction.
  • This NHP model replicates key features of human cardiac pathology, including fibrosis.
  • The NHP TAC model provides a valuable platform for preclinical research in cardiovascular disease and therapeutic development.