High red cell distribution width (RDW) has been increasingly recognized as a risk factor for cardiovascular diseases (CVDs), but the underlying mechanisms remain unknown. Our aim was to explore the associations between RDW and plasma proteins implicated in the pathogenesis of CVD using a targeted proteomics panel. RDW and 88 plasma proteins were measured in a population-based cohort study (n = 4726), Malmö Diet and Cancer-Cardiovascular Cohort (MDC-CC). A random 2/3 of the cohort was used as discovery sample and remaining 1/3 was used for replication. Multiple linear regression was used to assess the associations between RDW and plasma proteins, with adjustments for age, sex, and other potential confounders. Proteins with Bonferroni-corrected significant associations with RDW in the discovery sub-cohort were validated in the replication cohort. Thirteen of 88 plasma proteins had significant associations with RDW in the discovery sample, after multivariate adjustments. Eleven of them were also significant in the replication sample, including SIR2-like protein 2 (SIRT2), stem cell factor (SCF, inversely), melusin (ITGB1BP2), growth differentiation factor-15 (GDF-15), matrix metalloproteinase-7 (MMP-7), hepatocyte growth factor (HGF), chitinase-3-like protein 1 (CHI3L1), interleukin-8 (IL-8), CD40 ligand (CD40-L), urokinase plasminogen activator surface receptor (U-PAR) and matrix metalloproteinase-3 (MMP-3). Several proteins from this targeted proteomics panel were associated with RDW in this cohort. These proteins could potentially be linked to the increased cardiovascular risk in individuals with high RDW.

中文翻译：

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一般人群中红细胞分布宽度与血浆蛋白之间的关联


高红细胞分布宽度（RDW）越来越被认为是心血管疾病（CVD）的危险因素，但其潜在机制仍不清楚。我们的目的是使用靶向蛋白质组学面板探索 RDW 和与 CVD 发病机制相关的血浆蛋白之间的关联。在基于人群的队列研究 (n = 4726)、马尔默饮食和癌症心血管队列 (MDC-CC) 中测量了 RDW 和 88 种血浆蛋白。队列中随机 2/3 用作发现样本，其余 1/3 用于复制。使用多元线性回归评估 RDW 和血浆蛋白之间的关联，并对年龄、性别和其他潜在混杂因素进行调整。经过 Bonferroni 校正的蛋白质与发现子队列中 RDW 的显着关联在复制队列中得到了验证。经过多变量调整后，发现样本中 88 种血浆蛋白中有 13 种与 RDW 显着相关。其中 11 个在复制样本中也很重要，包括 SIR2 样蛋白 2 (SIRT2)、干细胞因子 (SCF，相反)、melusin (ITGB1BP2)、生长分化因子-15 (GDF-15)、基质金属蛋白酶-7 (MMP-7)、肝细胞生长因子 (HGF)、几丁质酶 3 样蛋白 1 (CHI3L1)、白细胞介素 8 (IL-8)、CD40 配体 (CD40-L)、尿激酶纤溶酶原激活剂表面受体 (U-PAR) ) 和基质金属蛋白酶-3 (MMP-3)。该靶向蛋白质组学组中的几种蛋白质与该队列中的 RDW 相关。这些蛋白质可能与高 RDW 个体心血管风险增加有关。