Kapoor Arunima, Gaubert Aimée, Marshall Anisa, Meier Irene B, Yew Belinda, Ho Jean K, Blanken Anna E, Dutt Shubir, Sible Isabel J, Li Yanrong, Jang Jung Yun, Brickman Adam M, Rodgers Kathleen, Nation Daniel A
Department of Psychological Science, University of California, Irvine, Irvine, CA, United States.
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States.
Front Aging Neurosci. 2021 Sep 28;13:711784. doi: 10.3389/fnagi.2021.711784. eCollection 2021.
Cerebral small vessel disease (SVD) is associated with increased risk of stroke and dementia. Progressive damage to the cerebral microvasculature may also trigger angiogenic processes to promote vessel repair. Elevated levels of circulating endothelial progenitor cells (EPCs) and pro-angiogenic signaling proteins are observed in response to vascular injury. We aimed to examine circulating levels of EPCs and proangiogenic proteins in older adults with evidence of SVD. Older adults (ages 55-90) free of dementia or stroke underwent venipuncture and brain magnetic resonance imaging (MRI). Flow cytometry quantified circulating EPCs as the number of cells in the lymphocyte gate positively expressing EPC surface markers (CD34+CD133+CD309+). Plasma was assayed for proangiogenic factors (VEGF-A, VEGF-C, VEGF-D, Tie-2, and Flt-1). Total SVD burden score was determined based on MRI markers, including white matter hyperintensities, cerebral microbleeds and lacunes. Sixty-four older adults were included. Linear regression revealed that older adults with higher circulating EPC levels exhibited greater total SVD burden [β = 1.0 × 10, 95% CI (0.2, 1.9), = 0.019], after accounting for age and sex. Similarly, a positive relationship between circulating VEGF-D and total SVD score was observed, controlling for age and sex [β = 0.001, 95% CI (0.000, 0.001), = 0.048]. These findings suggest that elevated levels of circulating EPCs and VEGF-D correspond with greater cerebral SVD burden in older adults. Additional studies are warranted to determine whether activation of systemic angiogenic growth factors and EPCs represents an early attempt to rescue the vascular endothelium and repair damage in SVD.
脑小血管病（SVD）与中风和痴呆风险增加相关。对脑微血管的渐进性损伤也可能触发血管生成过程以促进血管修复。在血管损伤后，可观察到循环内皮祖细胞（EPCs）和促血管生成信号蛋白水平升高。我们旨在检查有SVD证据的老年人中EPCs和促血管生成蛋白的循环水平。无痴呆或中风的老年人（55 - 90岁）接受静脉穿刺和脑磁共振成像（MRI）检查。流式细胞术将循环EPCs定量为淋巴细胞门中阳性表达EPC表面标志物（CD34 + CD133 + CD309 +）的细胞数量。检测血浆中的促血管生成因子（VEGF - A、VEGF - C、VEGF - D、Tie - 2和Flt - 1）。根据MRI标志物，包括白质高信号、脑微出血和腔隙，确定总的SVD负担评分。纳入了64名老年人。线性回归显示，在考虑年龄和性别后，循环EPC水平较高的老年人表现出更大的总SVD负担[β = 1.0×10，95%可信区间（0.2，1.9），P = 0.019]。同样，在控制年龄和性别后，观察到循环VEGF - D与总SVD评分之间呈正相关[β = 0.001，95%可信区间（0.000，0.001），P = 0.048]。这些发现表明，循环EPCs和VEGF - D水平升高与老年人更大的脑SVD负担相对应。有必要进行更多研究以确定全身血管生成生长因子和EPCs的激活是否代表了挽救血管内皮和修复SVD损伤的早期尝试。
