控制心血管代谢危险因素是有效防控心血管疾病的最佳策略。动物研究表明，生命早期所暴露的营养状况对成年后诸多心血管代谢危险因素的影响不仅局限于一代，而是可能存在跨代影响效应，但尚无法在人群研究中直接验证，且机制不明。本项目中，我们首次建立了以家庭为研究单位的中国饥荒队列，其中包括生命早期暴露饥荒的父母（F1代）及其子女（F2代）；利用该队列，拟分析F1生命早期暴露饥荒对F1和F2成年后心血管代谢危险因素的跨代影响，以及F1和F2成年期营养状况在其中发挥的调节作用；比较母系暴露和父系暴露以及父母一方暴露和双方暴露，对后代成年期心血管代谢危险因素的影响能力是否存在差异；从全基因组水平研究在上述跨代影响过程中起中介作用的DNA甲基化位点，进行表观遗传机制探讨；在动物实验中，进一步探讨出生后适当的膳食干预是否能阻断或逆转上述跨代影响。最终，从整个生命历程视角提出适合我国国情的心血管疾病防控方案。

Controlling the cardiometabolic risk factors is considered to be the best strategy to efficiently prevent the incidence of cardiovascular disease. Recently, rodent studies showed that the long-term effects of early-life exposure to under-nutrition on cardiometabolic risk factors may not be limited to one generation even in the absence of further environmental stressors. However, there is as yet no direct human study that has examined whether any prenatal effects on cardiometabolic risk may transmit to subsequent generations and the underlying mechanisms involved in for any potential trans-generational effects. In this project, we firstly established the Chinese famine cohort based on family, in which two generations (i.e. the parents (F1) who exposed to famine in early-life period and their offspring (F2)) were involved. Secondly, using this cohort, we will clarify the trans-generational effects of early-life exposure to famine on cardiometabolic risk factors in adulthood in two consecutive generations and study the interactive effects of early-life exposure to famine and dietary pattern in adulthood on cardiometabolic risk factors in two consecutive generations; compare the trans-generational effects of maternal and paternal exposure as well as one parent and both parents exposure to famine on offspring cardiometabolic risk factors in adulthood; and explore whether the abovementioned trans-generational effects of early-life exposure to famine on cardiometabolic risk factors in adulthood are mediated by DNA methylation. Thirdly, we will investigate whether the prenatal nutrient deprivation–induced adverse effects on cardiometabolic risk factors in two consecutive generations can be reversed with the introduction of early postnatal calorie restriction in a mice model of intra-uterine nutrition restriction. Finally, we will propose the specific prevention and control measures of cardiovascular risk factors from the view of life course and then to curb the highly epidemic cardiovascular diseases in China.