Division of Cardiology, Emory University School of Medicine, Atlanta, GA.
Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA.
J Am Heart Assoc. 2017 Oct 3;6(10):e006245. doi: 10.1161/JAHA.117.006245.
Lower levels of circulating progenitor cells (PCs) reflect impaired endogenous regenerative capacity and are associated with aging, vascular disease, and poor outcomes. Whether biologic sex and sex hormones influence PC numbers remains a subject of controversy. We sought to determine sex differences in circulating PCs in both healthy persons and patients with coronary artery disease, and to determine their association with sex hormone levels.
In 642 participants (mean age 48 years, 69% women, 23% black) free from cardiovascular disease, we measured circulating PC counts as CD45 mononuclear cells coexpressing CD34 and its subsets expressing CD133, chemokine (C-X-C motif) receptor 4, and vascular endothelial growth factor receptor 2 epitopes using flow cytometry. Testosterone and estradiol levels were measured. After adjustment for age, cardiovascular risk factors, and body mass, CD34 (β=-23%, <0.001), CD34/CD133 (β=-20%, =0.001), CD34/chemokine (C-X-C motif) receptor 4-positive (β=-24%, <0.001), and CD34/chemokine (C-X-C motif) receptor 4-positive/CD133 (β=-21%, =0.001) PC counts, but not vascular endothelial growth factor receptor 2-positive PC counts were lower in women compared with men. Estradiol levels positively correlated with hematopoietic, but not vascular endothelial growth factor receptor 2- positive PC counts in women (<0.05). Testosterone levels and PC counts were not correlated in men. These findings were replicated in an independent cohort with prevalent coronary artery disease.
Women have lower circulating hematopoietic PC levels compared with men. Estrogen levels are modestly associated with PC levels in women. Since PCs are reflective of endogenous regenerative capacity, these findings may at least partly explain the rise in adverse cardiovascular events in women with aging and menopause.
循环祖细胞（PCs）水平较低反映了内源性再生能力受损，与衰老、血管疾病和不良预后有关。生物性别和性激素是否影响 PC 数量仍然存在争议。我们试图确定健康人群和冠心病患者循环 PCs 的性别差异，并确定其与性激素水平的关系。
在 642 名无心血管疾病的参与者（平均年龄 48 岁，69%为女性，23%为黑人）中，我们使用流式细胞术测量了循环 PC 计数，作为 CD45 单核细胞共同表达 CD34 及其表达 CD133、趋化因子（C-X-C 基序）受体 4 和血管内皮生长因子受体 2 表位的亚群。测量了睾酮和雌二醇水平。在调整年龄、心血管危险因素和体重后，CD34（β=-23%，<0.001）、CD34/CD133（β=-20%，=0.001）、CD34/趋化因子（C-X-C 基序）受体 4-阳性（β=-24%，<0.001）和 CD34/趋化因子（C-X-C 基序）受体 4-阳性/CD133（β=-21%，=0.001）PC 计数，但血管内皮生长因子受体 2-阳性 PC 计数在女性中低于男性。雌二醇水平与女性造血 PC 计数呈正相关，但与血管内皮生长因子受体 2-阳性 PC 计数无关（<0.05）。在男性中，睾酮水平与 PC 计数无关。这些发现在患有冠心病的独立队列中得到了复制。
与男性相比，女性的循环造血 PC 水平较低。雌激素水平与女性的 PC 水平有一定的相关性。由于 PCs 反映了内源性再生能力，这些发现至少可以部分解释女性在衰老和绝经期间不良心血管事件的增加。
