Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, Colorado, USA.
Adv Wound Care (New Rochelle). 2021 Apr;10(4):174-190. doi: 10.1089/wound.2018.0894. Epub 2020 Jul 7.
Ischemic heart disease accounts for over 20% of all deaths worldwide. As the global population faces a rising burden of chronic diseases, such as hypertension, hyperlipidemia, and diabetes, the prevalence of heart failure due to ischemic heart disease is estimated to increase. We sought to develop a model that may more accurately identify therapeutic targets to mitigate the development of heart failure following myocardial infarction (MI). Having utilized fetal large mammalian models of scarless wound healing, we proposed a fetal ovine model of myocardial regeneration after MI. Use of this model has identified critical pathways in the mammalian response to MI, which are differentially activated in the regenerative, fetal mammalian response to MI when compared to the reparative, scar-forming, adult mammalian response to MI. While the foundation of myocardial regeneration research has been built on zebrafish and rodent models, effective therapies derived from these disease models have been lacking; therefore, we sought to develop a more representative ovine model of myocardial regeneration after MI to improve the identification of therapeutic targets designed to mitigate the development of heart failure following MI. To develop therapies aimed at mitigating this rising burden of disease, it is critical that the animal models we utilize closely reflect the physiology and pathology we observe in human disease. We encourage use of this ovine large mammalian model to facilitate identification of therapies designed to mitigate the growing burden of heart failure.
缺血性心脏病占全球所有死亡人数的 20%以上。随着全球人口面临高血压、高血脂和糖尿病等慢性疾病负担的增加，预计因缺血性心脏病导致的心力衰竭的患病率将会上升。我们试图开发一种模型，以更准确地确定治疗靶点，减轻心肌梗死后心力衰竭的发展。我们利用无瘢痕伤口愈合的胎龄大型哺乳动物模型，提出了心肌梗死后绵羊模型的心肌再生。使用该模型已确定了哺乳动物对心肌梗死后反应的关键途径，与修复性、形成瘢痕的成年哺乳动物对心肌梗死后的反应相比，这些途径在再生性、胎龄哺乳动物对心肌梗死后的反应中被不同程度地激活。虽然心肌再生研究的基础是建立在斑马鱼和啮齿动物模型上，但这些疾病模型中缺乏有效的治疗方法；因此，我们试图开发一种更具代表性的绵羊模型来研究心肌梗死后的再生，以提高治疗靶点的识别，从而减轻心肌梗死后心力衰竭的发展。为了开发旨在减轻这种疾病负担上升的治疗方法，我们使用的动物模型必须密切反映我们在人类疾病中观察到的生理学和病理学。我们鼓励使用这种绵羊大型哺乳动物模型，以促进识别旨在减轻日益增长的心力衰竭负担的治疗方法。
