Laboratory of Experimental Cardiology, UMC Utrecht, Utrecht University, Utrecht, the Netherlands.
Laboratory of Experimental Cardiology, UMC Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, Utrecht University, Utrecht, the Netherlands; Laboratory for Clinical Chemistry and Haematology, UMC Utrecht, Utrecht University, Utrecht, the Netherlands.
Atherosclerosis. 2019 Dec;291:114-121. doi: 10.1016/j.atherosclerosis.2019.10.009. Epub 2019 Oct 11.
Women who develop preeclampsia during pregnancy are at a higher risk for developing cardiovascular disease. As platelets are affected by preeclampsia, we set out to identify whether platelets carry information in their transcriptome on cardiovascular risk in women with former preeclampsia.
Platelets were isolated from asymptomatic women with previous preeclampsia, who underwent screening with coronary computed tomography angiography. Platelet RNA was isolated and used to construct gene networks using an unbiased approach. Platelet gene modules assembled from the network were related to risk factors and clinical traits of these women, including coronary artery calcium scores (CACS).
We found multiple gene modules which correlated with CACS (correlation coefficients: 0.44 to 0.59, p = 0.05 to 0.007). The genes from two clinically relevant modules were expressed at a higher level in the group with calcifications (p = 3.9 × 10 and 0.02) and enriched for platelet-related gene-sets such as platelet activation. The first of these modules was also enriched (p = 0.0546) for genes mapped to known coronary artery disease susceptibility loci. Additional unbiased network analyses in platelet RNA of patients with overt cardiovascular disease underlined the importance of the identified modules for disease by high preservation. (p = 1.6 × 10 to 1.7 × 10).
We found platelet RNA modules that correlated with CACS in asymptomatic women with previous preeclampsia. Whether or not platelets directly contribute to this disease trajectory, or reflect the underlying plaque substrate remains to be determined, but enrichment for coronary artery disease susceptibility genes emphasizes the importance for the disease.
怀孕期间发生子痫前期的女性发生心血管疾病的风险更高。由于血小板受子痫前期影响，我们着手确定以前患有子痫前期的女性的血小板转录组中是否存在与心血管风险相关的信息。
从无症状的以前患有子痫前期的女性中分离血小板，这些女性接受了冠状动脉计算机断层扫描血管造影检查。分离血小板 RNA，并用无偏倚的方法构建基因网络。从网络中组装的血小板基因模块与这些女性的危险因素和临床特征相关，包括冠状动脉钙评分 (CACS)。
我们发现了多个与 CACS 相关的基因模块（相关系数：0.44 至 0.59，p=0.05 至 0.007）。两个具有临床相关性的模块中的基因在钙化组中的表达水平更高（p=3.9×10 和 0.02），并富含血小板相关基因集，如血小板激活。这些模块中的第一个模块也富含（p=0.0546）映射到已知冠心病易感性基因座的基因。对明显患有心血管疾病的患者的血小板 RNA 进行额外的无偏网络分析，强调了所鉴定模块对疾病的重要性，因为其保存完好。（p=1.6×10 至 1.7×10）。
我们在以前患有子痫前期的无症状女性的血小板 RNA 中发现了与 CACS 相关的模块。血小板是否直接导致这种疾病的发生轨迹，或者是否反映了潜在的斑块基质仍有待确定，但对冠心病易感性基因的富集强调了其对疾病的重要性。
