When the liver is in poor condition, so is the heart - cardiac remodelling in MASH mouse models.

IF 6.7 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Sebastian Bott, Justine Lallement, Alice Marino, Evangelos-Panagiotis Daskalopoulos, Christophe Beauloye, Hrag Esfahani, Chantal Dessy, Isabelle Anne Leclercq
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引用次数: 0

Abstract

Metabolic dysfunction-associated steatohepatitis (MASH) confers a risk for cardiovascular diseases in patients. Animal models may help exploring the mechanisms linking liver and heart diseases. Hence, we explored the cardiac phenotype in two MASH mouse models: foz/foz mice fed a high-fat diet (HFD) for 24 or 60 weeks and C57BL/6J mice fed a high-fat-, high-cholesterol-, and high-fructose diet for 60 weeks. Angiotensin II (AngII) was used as an additional cardiovascular stressor for 4 weeks in 10 weeks HFD-fed foz/foz mice. Foz/foz mice with fibrosing MASH developed cardiac hypertrophy with adverse cardiac remodelling not seen in WT similarly fed the HFD. AngII caused hypertension and up-regulated the expression of genes contributing to pathological cardiac hypertrophy (Nppa, Myh7) more severely so in foz/foz mice than in controls. After 60 weeks of HFD, while liver disease had progressed to burn-out non steatotic MASH with hepatocellular carcinoma in 50% of the animals, the cardiomyopathy did not. In an independent model (C57BL/6J mice fed a fat-, cholesterol- and fructose-rich diet), moderate fibrosing MASH is associated with cardiac fibrosis and dysregulation of genes involved in pathological remodelling (Col1a1, Col3a1, Vim, Myh6, Slc2a1). Thus, animals with MASH present consistent adverse structural changes in the heart with no patent alteration of cardiac function even when stressed with exogenous AngII. Liver disease, and likely not overfeeding or aging alone, is associated with this cardiac phenotype. Our findings support foz/foz mice as suitable for studying links between MASH and heart structural changes ahead of heart failure.

当肝脏状况不佳时,心脏也会受到影响--MASH 小鼠模型中的心脏重塑。
代谢功能障碍相关性脂肪性肝炎(MASH)会给患者带来罹患心血管疾病的风险。动物模型可能有助于探索肝脏和心脏疾病的关联机制。因此,我们对两种MASH小鼠模型的心脏表型进行了研究:以高脂饮食(HFD)喂养24周或60周的foz/foz小鼠和以高脂、高胆固醇和高果糖饮食喂养60周的C57BL/6J小鼠。血管紧张素 II(AngII)是一种额外的心血管应激源,在喂食高脂饮食 10 周的 foz/foz 小鼠中使用 4 周。患有纤维化 MASH 的 Foz/foz 小鼠出现了心脏肥大,并伴有不利的心脏重塑,而喂食高氟日粮的 WT 小鼠却没有出现这种情况。AngII 在 foz/foz 小鼠中引起高血压,并上调导致病理性心肌肥厚的基因(Nppa、Myh7)的表达,这种情况在 foz/foz 小鼠中比在对照组中更为严重。高密度脂蛋白饮食 60 周后,50% 的动物肝脏疾病发展为烧竭性非脂肪性 MASH,并伴有肝细胞癌,但心肌病却没有发展。在一个独立的模型中(以富含脂肪、胆固醇和果糖的食物喂养的 C57BL/6J 小鼠),中度纤维化的 MASH 与心脏纤维化和参与病理重塑的基因(Col1a1、Col3a1、Vim、Myh6、Slc2a1)失调有关。因此,患有 MASH 的动物即使在外源性 AngII 的压力下,心脏结构也会发生持续的不良变化,但心脏功能却不会发生明显改变。这种心脏表型与肝脏疾病有关,而可能不仅仅是过度喂养或衰老。我们的研究结果表明,foz/foz 小鼠适合用于研究 MASH 与心力衰竭前心脏结构变化之间的联系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical science
Clinical science 医学-医学:研究与实验
CiteScore
11.40
自引率
0.00%
发文量
189
审稿时长
4-8 weeks
期刊介绍: Translating molecular bioscience and experimental research into medical insights, Clinical Science offers multi-disciplinary coverage and clinical perspectives to advance human health. Its international Editorial Board is charged with selecting peer-reviewed original papers of the highest scientific merit covering the broad spectrum of biomedical specialities including, although not exclusively: Cardiovascular system Cerebrovascular system Gastrointestinal tract and liver Genomic medicine Infection and immunity Inflammation Oncology Metabolism Endocrinology and nutrition Nephrology Circulation Respiratory system Vascular biology Molecular pathology.
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