Myocardial Ischemia and Mobilization of Circulating Progenitor Cells.
Myocardial Ischemia and Mobilization of Circulating Progenitor Cells.
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心肌缺血和循环祖细胞的动员。
DOI：
10.1161/jaha.117.007504
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发表时间：
2018
影响因子：
5.4
通讯作者：
Pim
中科院分区：
文献类型：
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作者：
Hammadah,Muhammad;SammanTahhan,Ayman;Mheid,IbharAl;Wilmot,Kobina;Ramadan,Ronnie;Kindya,BryanR;Kelli,HevalM;O'Neal,WesleyT;Sandesara,Pratik;Sullivan,Samaah;Almuwaqqat,Zakaria;Obideen,Malik;Abdelhadi,Naser;Alkhoder,Ayman;Pim
背景冠状动脉疾病患者的祖细胞（PC）对短暂心肌缺血的反应尚不清楚。我们的目的是调查PC对运动诱导的心肌缺血（ExMI）的反应，并将其与药理学stresstesting.Methods和ResultsA在运动（69%）或药理学应力（31%）期间，共356例稳定型冠状动脉疾病患者进行了99 mTc-甲氧基异丁基异腈心肌灌注成像。通过流式细胞术计数CD 34+和CD 34 +/趋化因子（C-X-C基序）受体4 PC。使用线性回归模型比较有和无心肌缺血患者的PC计数变化。对血管内皮生长因子和基质衍生因子-1 α进行定量。平均年龄为63±9岁; 76%为男性。运动和药物负荷试验期间ExMI的发生率分别为31%和41%。ExMI患者应激后CD 34 +/趋化因子（C-X-C基序）受体4显著降低（-18%，P =0.01），与缺血程度呈负相关（r=-0.19，P =0.003）。相比之下，非ExMI患者的CD 34 +/趋化因子（C-X-C基序）受体4表达增加（14.7%，P =0.02），而那些经历药物应激的患者没有变化。运动负荷试验组血浆血管内皮生长因子水平升高（15%，P <0.001）。然而，在ExMI患者中，基质衍生因子-1 α水平的变化与PC计数的变化呈负相关。（P=0.03），表明运动时基质衍生因子-1 α水平变化较大的患者PC水平下降幅度较大。（C-X-C基序）受体4 PC，可能至少部分归因于基质衍生因子-1 α介导的PC归巢至缺血心肌。这种摄取PC的生理后果及其治疗意义需要进一步研究。
BackgroundThe response of progenitor cells (PCs) to transient myocardial ischemia in patients with coronary artery disease remains unknown. We aimed to investigate the PC response to exercise‐induced myocardial ischemia (ExMI) and compare it to flow mismatch during pharmacological stress testing.Methods and ResultsA total of 356 patients with stable coronary artery disease underwent 99mTc‐sestamibi myocardial perfusion imaging during exercise (69%) or pharmacological stress (31%). CD34+and CD34+/chemokine (C‐X‐C motif) receptor 4 PCs were enumerated by flow cytometry. Change in PC count was compared between patients with and without myocardial ischemia using linear regression models. Vascular endothelial growth factor and stromal‐derived factor‐1α were quantified. Mean age was 63±9 years; 76% were men. The incidence of ExMI was 31% and 41% during exercise and pharmacological stress testing, respectively. Patients with ExMI had a significant decrease in CD34+/chemokine (C‐X‐C motif) receptor 4 (−18%,P=0.01) after stress that was inversely correlated with the magnitude of ischemia (r=−0.19,P=0.003). In contrast, patients without ExMI had an increase in CD34+/chemokine (C‐X‐C motif) receptor 4 (14.7%,P=0.02), and those undergoing pharmacological stress had no change. Plasma vascular endothelial growth factor levels increased (15%,P<0.001) in all patients undergoing exercise stress testing regardless of ischemia. However, the change in stromal‐derived factor‐1α level correlated inversely with the change in PC counts in those with ExMI (P=0.03), suggesting a greater decrease in PCs in those with a greater change in stromal‐derived factor‐1α level with exercise.ConclusionsExMI is associated with a significant decrease in circulating levels of CD34+/chemokine (C‐X‐C motif) receptor 4 PCs, likely attributable, at least in part, to stromal‐derived factor‐1α–mediated homing of PCs to the ischemic myocardium. The physiologic consequences of this uptake of PCs and their therapeutic implications need further investigation.