Worse clinical outcomes in acute myocardial infarction patients with type 2 diabetes mellitus: relevance to impaired endothelial progenitor cells mobilization.
Worse clinical outcomes in acute myocardial infarction patients with type 2 diabetes mellitus: relevance to impaired endothelial progenitor cells mobilization.
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患有 2 型糖尿病的急性心肌梗死患者的临床结果更差：与内皮祖细胞动员受损的相关性
DOI：
10.1371/journal.pone.0050739
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Xu B
中科院分区：
文献类型：
--
作者：
Ling L;Shen Y;Wang K;Jiang C;Fang C;Ferro A;Kang L;Xu B
背景：虽然2型糖尿病（T2DM）患者急性心肌梗死（AMI）的临床预后明显差于非糖尿病患者，但其原因尚不清楚。我们假设这可能与骨髓来源的内皮祖细胞（EPCs）动员受损有关。我们观察了62例伴有或不伴有T2DM的AMI患者的短期骨髓EPCs动员和长期临床结果，并研究了AMI后大鼠糖尿病模型中EPCs水平和骨髓通路的变化。T2DM患者在AMI后一个月内表现出延迟（峰值时间：糖尿病vs非糖尿病：第7天vs第5天）和EPCs动员减少（糖尿病vs非糖尿病：285±56/106个单核细胞（MNCs） vs 431±88/106个MNCs， p<0.05）。2型糖尿病患者血浆中VEGF、SDF-1α以及hsCRP水平较高。在平均2.26年的随访中，T2DM患者表现出明显的LVEF下降和临床事件的增加。血糖（HR 2.01, 95% CI 1.42-2.85, p = 0.008）、第一天EPC （HR 0.974, 95% CI 0.952-0.997, p = 0.02）和第7天EPCs （HR 0.966, 95% CI 0.945-0.988, p = 0.003）是心血管死亡率的独立预后变量。在糖尿病大鼠AMI模型中，循环EPCs减少，骨髓中phospho-Akt、phospho-eNOS、HIF、MMP-9和MMP-9活性降低，心功能受损，血管生成和左心室重构增加。结论/意义糖尿病患者骨髓EPCs动员延迟和减少，HIF/p-Akt/p-eNOS/MMP-9信号受损。这可能导致2型糖尿病患者心功能的恶化和临床结果的恶化。
Background Although the clinical outcome of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus (T2DM) is well established to be worse than for non-diabetic patients, the reasons for this remain unclear. We hypothesized that this may be related to impairment of bone marrow-derived endothelial progenitor cells (EPCs) mobilization. Methodology/Principal Findings We observed short term bone marrow EPCs mobilization and long term clinical outcomes in 62 AMI patients with or without T2DM and investigated EPCs levels as well as bone marrow pathway changes in a rat model of diabetes after AMI. Patients with T2DM exhibited a delay (peak time diabetics vs. non-diabetics: day 7 vs. day 5) and a decrease in EPCs mobilization (diabetics vs. non-diabetics: 285±56/106 mononuclear cells (MNCs) vs. 431±88/106 MNCs, p<0.05) within one month after AMI. Plasma levels of VEGF and SDF-1α as well as of hsCRP were higher in T2DM patients. Over a mean of 2.26 years follow-up, T2DM patients exhibited a pronounced decrease in LVEF as well as an increase in clinical events. Glucose (HR 2.01, 95% CI 1.42–2.85, p = 0.008), first day EPC (HR 0.974, 95% CI 0.952–0.997, p = 0.02) and seven day EPCs (HR 0.966, 95% CI 0.945–0.988, p = 0.003) were independent prognostic variables for cardiovascular mortality. In a diabetic rat model of AMI, decreased circulating EPCs was accompanied by lower expression of phospho-Akt, phospho-eNOS, HIF, MMP-9 and MMP-9 activity in the bone marrow as well as impaired cardiac function, angiogenesis and increased left ventricle remodeling. Conclusions/Significance Bone marrow EPCs mobilization is delayed and reduced in diabetes, with impaired HIF/p-Akt/p-eNOS/MMP-9 signaling. This is likely to contribute to the deterioration in cardiac function and worsened clinical outcome seen in patients with T2DM.
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