Regulation of circulating progenitor cells in left ventricular dysfunction.
Regulation of circulating progenitor cells in left ventricular dysfunction.
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DOI：
10.1161/circheartfailure.109.879437
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发表时间：
2010-09
期刊：
影响因子：
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通讯作者：
Simari RD
中科院分区：
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作者：
Boilson BA;Larsen K;Harbuzariu A;Delacroix S;Korinek J;Froehlich H;Bailey KR;Scott CG;Shapiro BP;Boerrigter G;Chen HH;Redfield MM;Burnett JC Jr;Simari RD
循环祖细胞（CD 34+细胞亚群）数量的减少已在有心血管疾病风险或存在心血管疾病的患者中得到证实。这些减少的介质仍然不确定。为了确定神经体液因子是否可以调节体内循环CD 34+细胞亚群，我们研究了左心室（LV）功能障碍的补充犬模型。研究了严重左室功能障碍的起搏模型和高血压肾包裹（RW）模型，其中犬随机接受醋酸脱氧皮质酮（DOCA）。定量循环CD 34+细胞亚群，包括造血前体细胞（HPC：CD 34 +/CD 45-/VEGFR 2-）和内皮祖细胞（EPC：CD 34 +/CD 45-/VEGFR 2+）。此外，还研究了盐皮质激素过量对正常狗循环祖细胞的影响。大多数循环CD 34+细胞表达CD 45模糊，不表达VEGFR 2，与HPC表型一致。HPC对起搏的反应降低，并且这种降低与血浆醛固酮水平相关（斯皮尔曼等级相关性=-0.67，p=0.03）。在RW模型中，给予DOCA导致HPC减少。在两种模型中均未观察到EPC变化。DOCA处理的正常狗表现出外周血中HPC的减少，但骨髓中没有与端粒酶活性降低相关的HPC。这是第一个研究表明，盐皮质激素过量，无论是内源性或外源性，在减少HPC的结果。这些数据表明，盐皮质激素可诱导祖细胞加速衰老，导致其存活率降低和数量下降。
Reductions in numbers of circulating progenitor cells (CD34+ cell subsets) have been demonstrated in patients at risk for, or in the presence of, cardiovascular disease. The mediators of these reductions remain undefined. To determine whether neurohumoral factors might regulate circulating CD34+ cell subsets in vivo, we studied complementary canine models of left ventricular (LV) dysfunction. A pacing model of severe LV dysfunction and a hypertensive renal wrap (RW) model in which dogs were randomized to receive deoxycorticosterone acetate (DOCA) were studied. Circulating CD34+ cell subsets including hematopoietic precursor cells (HPCs:CD34+/CD45dim/VEGFR2-) and endothelial progenitor cells (EPCs:CD34+/CD45-/VEGFR2+) were quantified. Additionally, the effect of mineralocorticoid excess on circulating progenitor cells in normal dogs was studied. The majority of circulating CD34+ cells expressed CD45 dimly and did not express VEGFR2, consistent with an HPC phenotype. HPCs were decreased in response to pacing, and this decrease correlated with plasma aldosterone levels (Spearman Rank correlation = -0.67, p=0.03). In the RW model, administration of DOCA resulted in decreased HPCs. No changes were seen in EPCs in either model. Normal dogs treated with DOCA exhibited a decrease in HPCs in peripheral blood but not bone marrow associated with decreased telomerase activity. This is the first study to demonstrate that mineralocorticoid excess, either endogenous or exogenous, results in reduction in HPCs. These data suggest that mineralocorticoids may induce accelerated senescence of progenitor cells leading to their reduced survival and decline in numbers.