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环境金属对心血管的影响概述:新的临床前和临床见解。

Overview of the cardiovascular effects of environmental metals: New preclinical and clinical insights.

机构信息

Department of Anesthesiology and Perioperative Medicine, University of Louisville School of Medicine, Louisville, KY, USA; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA; Cardiovascular Innovation Institute, Department of Cardiovascular and Thoracic Surgery, University of Louisville School of Medicine, Louisville, KY, USA.

Department of Internal Medicine, Division of Pulmonary Critical Care and Sleep Medicine, University of Nebraska Medical Center, Omaha, NE, USA.

出版信息

Toxicol Appl Pharmacol. 2022 Nov 1;454:116247. doi: 10.1016/j.taap.2022.116247. Epub 2022 Sep 17.

Abstract

Environmental causes of cardiovascular diseases (CVDs) are global health issues. In particular, an association between metal exposure and CVDs has become evident but causal evidence still lacks. Therefore, this symposium at the Society of Toxicology 2022 annual meeting addressed epidemiological, clinical, pre-clinical animal model-derived and mechanism-based evidence by five presentations: 1) An epidemiologic study on potential CVD risks of individuals exposed occupationally and environmentally to heavy metals; 2) Both presentations of the second and third were clinical studies focusing on the potential link between heavy metals and pulmonary arterial hypertension (PAH), by presenting altered blood metal concentrations of both non-essential and essential metals in the patients with PAH and potential therapeutic approaches; 3) Arsenic-induced atherosclerosis via inflammatory cells in mouse model; 4) Pathogenic effects on the heart by adult chronic exposure to very low-dose cadmium via epigenetic mechanisms and whole life exposure to low dose cadmium via exacerbating high-fat-diet-lipotoxicity. This symposium has brought epidemiologists, therapeutic industry, physicians, and translational scientists together to discuss the health risks of occupational and environmental exposure to heavy metals through direct cardiotoxicity and indirect disruption of homeostatic mechanisms regulating essential metals, as well as lipid levels. The data summarized by the presenters infers a potential causal link between multiple metals and CVDs and defines differences and commonalities. Therefore, summary of these presentations may accelerate the development of efficient preventive and therapeutic strategies by facilitating collaborations among multidisciplinary investigators.

摘要

环境因素是导致心血管疾病(CVDs)的全球性健康问题。特别是,金属暴露与 CVDs 之间的关联已经很明显,但因果关系的证据仍然缺乏。因此,本次研讨会在 2022 年毒理学会年会上,通过五个专题介绍了流行病学、临床、临床前动物模型和基于机制的证据:1)一项针对职业和环境重金属暴露个体潜在 CVD 风险的流行病学研究;2)第二个和第三个专题都是临床研究,重点探讨了重金属与肺动脉高压(PAH)之间的潜在联系,通过展示 PAH 患者血液中非必需和必需金属浓度的变化,以及潜在的治疗方法;3)砷通过炎症细胞在小鼠模型中诱导动脉粥样硬化;4)通过表观遗传机制在成年慢性暴露于极低剂量镉以及通过加剧高脂肪饮食脂质毒性在整个生命周期中暴露于低剂量镉对心脏的致病作用。本次研讨会汇集了流行病学家、治疗行业、医生和转化科学家,共同讨论职业和环境暴露于重金属通过直接心脏毒性和间接破坏调节必需金属和脂质水平的体内平衡机制对健康的风险。演讲者总结的数据推断出多种金属与 CVDs 之间存在潜在的因果关系,并确定了差异和共同点。因此,这些演讲的总结可能通过促进多学科研究人员之间的合作,加速开发有效的预防和治疗策略。

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