Maroun-Eid Charbel, Ortega-Hernández Adriana, Modrego Javier, Abad-Cardiel María, García-Donaire José Antonio, Reinares Leonardo, Martell-Claros Nieves, Gómez-Garre Dulcenombre
Unit of Hypertension, Área de Prevención Cardiovascular, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
Vascular Biology Research Laboratory, Hospital Clínico San Carlos-IdISSC, Madrid, Spain.
PLoS One. 2018 Jan 5;13(1):e0190494. doi: 10.1371/journal.pone.0190494. eCollection 2018.
Most hypertensive patients, despite a proper control of their cardiovascular risk factors, have cardiovascular complications, evidencing the importance of controlling and/or reversing target-organ damage. In this sense, endothelial dysfunction has been associated with the presence of cardiovascular risk factors and related cardiovascular outcomes. Since hypertension often clusters with other risk factors such as dyslipemia, diabetes and obesity, in this study we have investigated the effect of intensive multifactorial treatment on circulating vascular progenitor cell levels on high-risk hypertensive patients.
We included108 hypertensive patients receiving intensive multifactorial pharmacologic treatment and dietary recommendations targeting blood pressure, dyslipemia, hyperglycemia and weight for 12 months. After the treatment period, blood samples were collected and circulating levels of endothelial (CD34+/KDR+, CD34+/VE-cadherin+) and smooth muscle (CD14+/endoglin+) progenitor cells were identified by flow cytometry. Additionally, plasma concentration of vascular endothelial growth factor (VEGF) was determined by ELISA.
Most hypertensive patients (61±12 years, 47% men) showed cardiovascular parameters within normal ranges at baseline. Moreover, body mass index and the majority of the biochemical parameters (systolic and diastolic blood pressure, fasting glucose, total cholesterol, HDL-c, LDL-c, creatinine and hs-CRP) significantly decreased overtime. After 12 months of intensive treatment, CD34+/KDR+ and CD14+/endoglin+ levels did not change, but CD34+/VE-cadherin+ cells increased significantly at month 12 [0.9(0.05-0.14)% vs 0.05(0.02-0.09)% P<0.05]. However, VEGF plasma concentration decreased significantly overtime [89.1(53.9-218.7) vs [66.2(47.5-104.6) pg/mL, P<0.05].
Long-term intensive treatment in hypertensive patients further improves cardiovascular risk and increases circulating EPCs, suggesting that these cells could be a therapeutic target.
大多数高血压患者尽管对其心血管危险因素进行了适当控制，但仍有心血管并发症，这证明了控制和/或逆转靶器官损害的重要性。从这个意义上说，内皮功能障碍与心血管危险因素的存在及相关心血管结局有关。由于高血压常与血脂异常、糖尿病和肥胖等其他危险因素聚集在一起，在本研究中，我们调查了强化多因素治疗对高危高血压患者循环血管祖细胞水平的影响。
我们纳入了108例接受强化多因素药物治疗以及针对血压、血脂异常、高血糖和体重的饮食建议治疗12个月的高血压患者。治疗期结束后，采集血样，通过流式细胞术鉴定内皮祖细胞（CD34+/KDR+、CD34+/血管内皮钙黏蛋白+）和平滑肌祖细胞（CD14+/内皮糖蛋白+）的循环水平。此外，通过酶联免疫吸附测定法测定血管内皮生长因子（VEGF）的血浆浓度。
大多数高血压患者（61±12岁，47%为男性）在基线时心血管参数处于正常范围内。此外，体重指数和大多数生化参数（收缩压和舒张压、空腹血糖、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、肌酐和高敏C反应蛋白）随时间显著下降。强化治疗12个月后，CD34+/KDR+和CD14+/内皮糖蛋白+水平未发生变化，但CD34+/血管内皮钙黏蛋白+细胞在第12个月时显著增加[0.9(0.05 - 0.14)%对0.05(0.02 - 0.09)%，P<0.05]。然而，VEGF血浆浓度随时间显著下降[89.1(53.9 - 218.7)对[66.2(47.5 - 104.6) pg/mL，P<0.05]。
高血压患者的长期强化治疗可进一步改善心血管风险并增加循环内皮祖细胞，提示这些细胞可能是一个治疗靶点。
