Hamo Carine E, Muller Matthew, Rosenfeld Emily, Xia Yuhe, Akinlonu Adedoyin, Luttrell-Williams Elliot, Barrett Tessa J, Berger Jeffrey S
Department of Medicine, Center for the Prevention of Cardiovascular Disease, New York University School of Medicine, New York City, NY, USA.
Leon H. Charney Division of Cardiology, Department of Medicine, Cardiovascular Research Center, New York University School of Medicine, New York City, NY, USA.
Platelets. 2025 Dec;36(1):2459800. doi: 10.1080/09537104.2025.2459800. Epub 2025 Jan 30.
Cardiometabolic risk factors, obesity, diabetes and hyperlipidemia contribute to cardiovascular disease (CVD). While platelets are involved in CVD pathogenesis, the relationship between risk factor burden on platelet indices and the platelet transcriptome remains uncertain. Blood was collected from CVD-free adults, measuring platelet count, mean platelet volume (MPV), immature platelet fraction (IPF), and absolute immature platelet fraction (AIPF) by hemogram. Platelets were isolated and analyzed via RNA sequencing. Participants were stratified by number of cardiometabolic risk factors (diabetes, obesity, hyperlipidemia). We calculated median (IQR) values of platelet indices and p-for-trend via linear regression across risk factor burden. To evaluate the association between risk factor burden and platelet transcripts, we performed multivariable linear regression adjusting for age, sex, and race/ethnicity. Among 141 participants, (50.5 ± 14.8 years, 42% male, 26% Black) risk factor burden was associated with increasing platelet size, IPF, and AIPF but not platelet count. Platelet RNA sequencing identified 100 differentially expressed transcripts ( < .01; 66 upregulated, 34 downregulated). Gene ontology enrichment analysis demonstrated upregulated pathways of secondary metabolic processes (NES = 1.96, < .01), and hematopoietic stem cell proliferation (NES = 1.95, < .01). Greater cardiometabolic risk factor burden is associated with increased platelet size and immaturity and suggesting novel platelet-mediated mechanisms linking risk factor burden with CVD.
心脏代谢危险因素、肥胖、糖尿病和高脂血症会导致心血管疾病（CVD）。虽然血小板参与了心血管疾病的发病机制，但危险因素负荷对血小板指标和血小板转录组之间的关系仍不明确。从无心血管疾病的成年人中采集血液，通过血常规测量血小板计数、平均血小板体积（MPV）、未成熟血小板比例（IPF）和绝对未成熟血小板比例（AIPF）。通过RNA测序分离并分析血小板。参与者按心脏代谢危险因素（糖尿病、肥胖、高脂血症）的数量进行分层。我们通过线性回归计算血小板指标的中位数（IQR）值和趋势p值，以评估危险因素负荷。为了评估危险因素负荷与血小板转录本之间的关联，我们进行了多变量线性回归，并对年龄、性别和种族/族裔进行了调整。在141名参与者中（年龄50.5±14.8岁，男性42%，黑人26%），危险因素负荷与血小板大小、IPF和AIPF增加有关，但与血小板计数无关。血小板RNA测序确定了100个差异表达的转录本（<0.01；66个上调，34个下调）。基因本体富集分析显示次生代谢过程（NES = 1.96，<0.01）和造血干细胞增殖（NES = 1.95，<0.01）的通路上调。更大的心脏代谢危险因素负荷与血小板大小增加和不成熟有关，提示了将危险因素负荷与心血管疾病联系起来的新的血小板介导机制。
