A chronic moderate methionine administration induced hyperhomocysteinemia associated with cardiovascular disease phenotype in the sand rat Psammomys obesus.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2022-05-23 DOI:10.5603/FHC.a2022.0013
Fouzia Zerrouk, B. Chaouad, A. Ghoul, Naima Chalour, A. Moulahoum, Zineb Khiari, M. Cherifi, Souhila Aouichat, K. Houali, Y. Benazzoug
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Abstract

INTRODUCTION Cardiovascular diseases were defined as coronary artery, cerebrovascular, or peripheral arterial disease.Hyperhomocysteinemia (Hhcy) is an independent risk factor of cardiovascular diseases, including atherosclerosis. Our previous studies demonstrated the involvement of Hhcy in cardiovascular remodeling in the sand rat Psammomys obesus. MATERIAL AND METHODS An experimental Hhcy was induced, in the sand rat Psammomys obesus, by a daily intraperitoneal injection of 70 mg/kg of methionine for a total duration of 6 months. The impact of Hhcy on the cellular and matrix structures of the heart, aorta and liver was analyzed using histological techniques. Additionally we treated primary cultures of aortic smooth muscle cells (SMCs) with high concentration of methionine to investigate the effects of methionine at the cellular level. RESULTS A moderate Hhcy induced a significant increase in the extracellular matrix components particularly collagens which accumulated in the interstitial and perivascular spaces in the studied organs indicating a developing fibrosis. A liver steatosis was also observed following methionine treatment. Further analysis of the aorta showed that Hhcy also induced vascular alterations including SMCs reorientation and proliferation associated with aneurysm formation. CONCLUSIONS Our results show for the first time that Hhcy can induce a cardiovascular and liver diseases phenotype in Psammomys obesus, a species previously shown to be a good model for the studies of diabetes and other metabolism-related pathologies.
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慢性中等蛋氨酸给药诱导沙鼠高同型半胱氨酸血症与心血管疾病表型相关。
引言心血管疾病被定义为冠状动脉、脑血管或外周动脉疾病。高同型半胱氨酸血症(Hhcy)是包括动脉粥样硬化在内的心血管疾病的独立危险因素。我们先前的研究表明Hhcy参与沙鼠的心血管重塑。材料和方法在沙鼠中通过每天腹膜内注射70mg/kg蛋氨酸诱导实验性Hhcy,总持续时间为6个月。用组织学技术分析Hhcy对心脏、主动脉和肝脏细胞和基质结构的影响。此外,我们用高浓度甲硫氨酸处理主动脉平滑肌细胞(SMC)的原代培养物,以在细胞水平上研究甲硫氨酸的影响。结果中度Hhcy诱导细胞外基质成分显著增加,尤其是胶原,这些胶原积聚在所研究器官的间质和血管周围空间,表明纤维化正在发展。甲硫氨酸治疗后也观察到肝脏脂肪变性。对主动脉的进一步分析表明,Hhcy还诱导了血管改变,包括与动脉瘤形成相关的SMC重新定向和增殖。结论我们的研究结果首次表明,Hhcy可以诱导大沙鼠的心血管和肝脏疾病表型,该物种以前被证明是研究糖尿病和其他代谢相关病理的良好模型。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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