Martin-Ramirez Javier, Kok Maayke G M, Hofman Menno, Bierings Ruben, Creemers Esther E, Meijers Joost C M, Voorberg Jan, Pinto-Sietsma Sara-Joan
Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands.
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
PLoS One. 2014 Jun 23;9(6):e99890. doi: 10.1371/journal.pone.0099890. eCollection 2014.
To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis.
Patients with premature CAD (men <51 yr, women <56 yr) and their FDRs were included. Based on coronary calcification (CAC) scores FDRs were divided in a group of healthy subjects (CAC = 0) and subjects with subclinical atherosclerosis (CAC>0). We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs. FDRs with subclinical atherosclerosis had lower colony numbers compared with healthy FDRs, however this was not statistically significant, and BOEC proliferation was significantly impaired (OR = 0.45, 95% CI 0.21-0.96). Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs. Since a considerable number of premature CAD patients used statins, we studied the number of BOEC precursors as well as their proliferative capacity in ten individuals with subclinical atherosclerosis, before and after statin therapy. Interestingly, FDRs with subclinical atherosclerosis showed a significant increase in the number of BOEC colonies after statin therapy.
BOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration.
为研究冠心病（CAD）患者血管内皮的再生能力，我们培养了早发CAD患者及其一级亲属（FDR）的血源内皮祖细胞（BOECs）。此外，我们评估了他汀类药物治疗对亚临床动脉粥样硬化患者循环BOEC前体细胞的影响。
纳入早发CAD患者（男性<51岁，女性<56岁）及其FDR。根据冠状动脉钙化（CAC）评分，FDR被分为健康受试者组（CAC = 0）和亚临床动脉粥样硬化受试者组（CAC>0）。我们未观察到早发CAD患者与FDR在BOEC集落数量和增殖方面的差异。与健康FDR相比，患有亚临床动脉粥样硬化的FDR集落数量较少，然而这并无统计学意义，且BOEC增殖显著受损（OR = 0.45，95%CI 0.21 - 0.96）。出乎意料的是，早发CAD患者与健康FDR的BOEC集落数量和BOEC增殖情况相似。由于相当数量的早发CAD患者使用了他汀类药物，我们研究了10例亚临床动脉粥样硬化患者在他汀类药物治疗前后BOEC前体细胞的数量及其增殖能力。有趣的是，患有亚临床动脉粥样硬化的FDR在他汀类药物治疗后BOEC集落数量显著增加。
与健康对照相比，亚临床动脉粥样硬化患者的BOEC增殖受损。在这些患者中，他汀类药物治疗显著增加了循环BOEC前体细胞的数量及其增殖能力，揭示了他汀类药物对血管内皮再生的有益作用。
