Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN (A.S.P., S.Z., J.J.C., R.V.S.).
Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, (K.Z.).
Circ Res. 2024 Jun 21;135(1):138-154. doi: 10.1161/CIRCRESAHA.124.324559. Epub 2024 Apr 25.
The biological mechanisms linking environmental exposures with cardiovascular disease pathobiology are incompletely understood. We sought to identify circulating proteomic signatures of environmental exposures and examine their associations with cardiometabolic and respiratory disease in observational cohort studies.
We tested the relations of >6500 circulating proteins with 29 environmental exposures across the built environment, green space, air pollution, temperature, and social vulnerability indicators in ≈3000 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults) across 4 centers using penalized and ordinary linear regression. In >3500 participants from FHS (Framingham Heart Study) and JHS (Jackson Heart Study), we evaluated the prospective relations of proteomic signatures of the envirome with cardiovascular disease and mortality using Cox models.
Proteomic signatures of the envirome identified novel/established cardiovascular disease-relevant pathways including DNA damage, fibrosis, inflammation, and mitochondrial function. The proteomic signatures of the envirome were broadly related to cardiometabolic disease and respiratory phenotypes (eg, body mass index, lipids, and left ventricular mass) in CARDIA, with replication in FHS/JHS. A proteomic signature of social vulnerability was associated with a composite of cardiovascular disease/mortality (1428 events; FHS: hazard ratio, 1.16 [95% CI, 1.08-1.24]; =1.77×10; JHS: hazard ratio, 1.25 [95% CI, 1.14-1.38]; =6.38×10; hazard ratio expressed as per 1 SD increase in proteomic signature), robust to adjustment for known clinical risk factors.
Environmental exposures are related to an inflammatory-metabolic proteome, which identifies individuals with cardiometabolic disease and respiratory phenotypes and outcomes. Future work examining the dynamic impact of the environment on human cardiometabolic health is warranted.
环境暴露与心血管疾病发病机制之间的生物学机制尚不完全清楚。我们试图确定环境暴露的循环蛋白质组学特征，并在观察性队列研究中研究它们与心血管代谢和呼吸系统疾病的关联。
我们使用惩罚和普通线性回归，在 4 个中心的 CARDIA 研究（年轻人冠状动脉风险发展）中约 3000 名参与者中，测试了超过 6500 种循环蛋白与建筑环境、绿地、空气污染、温度和社会脆弱性指标中的 29 种环境暴露之间的关系。在 FHS（弗雷明汉心脏研究）和 JHS（杰克逊心脏研究）中的>3500 名参与者中，我们使用 Cox 模型评估了环境蛋白质组学特征与心血管疾病和死亡率的前瞻性关系。
环境蛋白质组学特征确定了新的/已建立的与心血管疾病相关的途径，包括 DNA 损伤、纤维化、炎症和线粒体功能。环境蛋白质组学特征与 CARDIA 中的心血管代谢疾病和呼吸系统表型（例如体重指数、脂质和左心室质量）广泛相关，在 FHS/JHS 中得到复制。社会脆弱性的蛋白质组学特征与心血管疾病/死亡率的综合指标相关（FHS：风险比 1.16 [95%CI 1.08-1.24]；=1.77×10；JHS：风险比 1.25 [95%CI 1.14-1.38]；=6.38×10；风险比表示每增加 1 个标准差的蛋白质组学特征），调整已知临床危险因素后仍然稳健。
环境暴露与炎症代谢蛋白质组学相关，该蛋白质组学可以识别患有心血管代谢疾病和呼吸系统表型和结局的个体。未来研究检查环境对人类心血管代谢健康的动态影响是有必要的。
