Large animal models of pressure overload-induced cardiac left ventricular hypertrophy to study remodelling of the human heart with aortic stenosis

Data de publicação: 01/01/2024

Autores da FMUP

• Joaquim Adelino Correia Ferreira Leite Moreira

  Autor

Participantes de fora da FMUP

• Beslika E.
• De Windt L.J.
• da Costa Martins P.A.

Unidades de investigação

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Pathologic cardiac hypertrophy is a common consequence of many cardiovascular diseases, including aortic stenosis (AS). AS is known to increase the pressure load of the left ventricle, causing a compensative response of the cardiac muscle, which progressively will lead to dilation and heart failure. At a cellular level, this corresponds to a considerable increase in the size of cardiomyocytes, known as cardiomyocyte hypertrophy, while their proliferation capacity is attenuated upon the first developmental stages. Cardiomyocytes, in order to cope with the increased workload (overload), suffer alterations in their morphology, nuclear content, energy metabolism, intracellular homeostatic mechanisms, contractile activity, and cell death mechanisms. Moreover, modifications in the cardiomyocyte niche, involving inflammation, immune infiltration, fibrosis, and angiogenesis, contribute to the subsequent events of a pathologic hypertrophic response. Considering the emerging need for a better understanding of the condition and treatment improvement, as the only available treatment option of AS consists of surgical interventions at a late stage of the disease, when the cardiac muscle state is irreversible, large animal models have been developed to mimic the human condition, to the greatest extend. Smaller animal models lack physiological, cellular and molecular mechanisms that sufficiently resemblance humans and in vitro techniques yet fail to provide adequate complexity. Animals, such as the ferret (Mustello purtorius furo), lapine (rabbit, Oryctolagus cunigulus), feline (cat, Felis catus), canine (dog, Canis lupus familiaris), ovine (sheep, Ovis aries), and porcine (pig, Sus scrofa), have contributed to research by elucidating implicated cellular and molecular mechanisms of the condition. Essential discoveries of each model are reported and discussed briefly in this review. Results of large animal experimentation could further be interpreted aiming at prevention of the disease progress or, alternatively, at regression of the implicated pathologic mechanisms to a physiologic state. This review summarizes the important aspects of the pathophysiology of LV hypertrophy and the applied surgical large animal models that currently better mimic the condition. © The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.

© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.

Keywords

• Animals; Aortic Valve Stenosis; Disease Models, Animal; Humans; Hypertrophy, Left Ventricular; Myocytes, Cardiac; Species Specificity; Ventricular Function, Left; Ventricular Pressure; Ventricular Remodeling; angiogenesis; animal model; aortic stenosis; Article; Canis; cat; cell death; cell population; disease model; heart left ventricle overload; heart muscle fibrosis; homeostasis; hypoxia; immunoregulation; inflammation; left ventricular hypertrophy; metabolic regulation; mitochondrion; muscle contractility; Mustela putorius furo; New Zealand White (rabbit); nonhuman; oxidative stress; pathophysiology; pig; ploidy; sarcomere; sheep; animal; aortic valve stenosis; cardiac muscle cell; heart left ventricle function; heart ventricle remodeling; heart ventricular pressure; human; left ventricular hypertrophy; metabolism; pathology; species difference