Abstract：
Per- and polyfluoroalkyl substances (PFAS) are a group of persistent and widespread environmental pollutants that represent a high concern for human health. They have been shown to be associated with several important physiological processes such as lipid metabolism and the immune system. Consequently, PFAS are suspected to play a role in cardiometabolic disease development. However, the evidence regarding associations between PFAS and overt cardiovascular disease and type 2 diabetes remains limited and inconsistent. To address this, we conducted a review of the epidemiological evidence. A deeper understanding of potential underlying molecular mechanisms may help to explain inconsistencies in epidemiological findings. Thus, to gain more mechanistic insight, we also summarized evidence from omics and laboratory studies into an adverse outcome pathway framework. Our observations indicate the potential for associations of PFAS with multiple molecular pathways that could have opposite associations with disease risk, which could be further modified by mixture composition, lifestyle factors or genetic polymorphisms. This identifies the need for exposome studies considering mixture effects, the use of multi-omics data to gain insight in relevant pathways and the integration of epidemiological and laboratory studies to enhance mechanistic understanding and causal inference. Improved comprehension is essential for environmental health risk assessments.
摘要：
全氟烷基和多氟烷基物质（PFAS）是一组持久性和广泛性的环境污染物，对人类健康具有高度关注。它们已被证明与一些重要的生理过程有关，例如脂质代谢和免疫系统。因此,PFAS被怀疑在心脏代谢疾病的发展中起作用。然而,关于PFAS与明显心血管疾病和2型糖尿病之间关联的证据仍然有限且不一致.为了解决这个问题，我们对流行病学证据进行了回顾.更深入地了解潜在的潜在分子机制可能有助于解释流行病学发现的不一致之处。因此，为了获得更多的机械洞察力，我们还将来自组学和实验室研究的证据总结为不良结局通路框架.我们的观察表明，PFAS与多种分子途径的潜在关联可能与疾病风险有相反的关联，可以通过混合物成分进一步改性，生活方式因素或遗传多态性。Thisidentifiestheneedforexposomestudiesconsideringmixtureeffects,使用多组学数据来深入了解相关通路，并整合流行病学和实验室研究以增强机理理解和因果推断。提高理解力对于环境健康风险评估至关重要。
