IRCCS MultiMedica, Milan, Italy.
Cardiovasc Res. 2013 Nov 1;100(2):192-200. doi: 10.1093/cvr/cvt153. Epub 2013 Jun 12.
Following acute myocardial infarction (AMI), pro-angiogenic progenitor cells (PCs) are released from the bone marrow into the circulation and home to the ischaemic site attracted by a chemokine gradient. It is unknown if components of this early homeostatic response might help forecast the long-term clinical outcome. This study investigates if the number and migratory activity of circulating PCs predict adverse events in patients with AMI (clinical trial: NCT01271309).
Basal counts and in vitro migratory activity of CD34/CD45/CD133/CXCR4 PCs and serum cytokine levels were assessed during the first 5 days after AMI in a consecutive series of 172 patients. Clinical outcomes of the study were death, repeat AMI, and new-onset heart failure at a 1-year follow-up. The association between PC counts and cytokine levels with the incidence of clinical outcomes was assessed by multivariable regression models. AMI patients who underwent an event showed higher serum stromal cell-derived factor 1α (SDF-1α) levels and reduced spontaneous motility of PCs in an in vitro migration assay when compared with event-free subjects. After adjustment for age, gender, the presence or absence of ST elevation, or diabetes, the percentage of PCs non-migrated towards vehicle or SDF-1α were both independent predictors of death or repeat AMI and new-onset heart failure (odds ratio [OR] = 2, P = 0.015 and OR = 1.90, P = 0.018, respectively). Moreover, serum SDF-1α levels predict adverse events (OR = 3.8, P = 0.007).
Biomarkers reflecting the migratory activity of circulating PCs may aid the assessment of secondary risk in AMI patients.
急性心肌梗死(AMI)后,促血管生成祖细胞(PCs)从骨髓释放到循环中,并在趋化因子梯度的吸引下归巢到缺血部位。目前尚不清楚这种早期内稳态反应的成分是否有助于预测 AMI 患者的长期临床结局。本研究旨在探讨循环 PCs 的数量和迁移活性是否可以预测 AMI 患者的不良事件(临床试验:NCT01271309)。
连续纳入 172 例 AMI 患者,在 AMI 后 5 天内评估 CD34/CD45/CD133/CXCR4 PCs 的基础计数和体外迁移活性以及血清细胞因子水平。研究的临床终点为 1 年随访时的死亡、再发 AMI 和新发心力衰竭。采用多变量回归模型评估 PC 计数和细胞因子水平与临床结局发生率之间的关系。与无事件组相比,发生事件的 AMI 患者的血清基质细胞衍生因子 1α(SDF-1α)水平较高,体外迁移试验中 PCs 的自发迁移能力降低。在调整年龄、性别、ST 段抬高的有无或糖尿病后,未向载体或 SDF-1α迁移的 PCs 百分比均为死亡或再发 AMI 和新发心力衰竭的独立预测因子(比值比 [OR] = 2,P = 0.015 和 OR = 1.90,P = 0.018)。此外,血清 SDF-1α 水平可预测不良事件(OR = 3.8,P = 0.007)。
反映循环 PCs 迁移活性的生物标志物可能有助于评估 AMI 患者的继发风险。