MicroRNA dysregulation in diabetic ischemic heart failure patients.
MicroRNA dysregulation in diabetic ischemic heart failure patients.
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糖尿病性缺血性心力衰竭患者的microRNA失调。
DOI：
10.2337/db11-0952
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发表时间：
2012-06
期刊：
影响因子：
7.7
通讯作者：
Martelli F
中科院分区：
文献类型：
--
作者：
Greco S;Fasanaro P;Castelvecchio S;D'Alessandra Y;Arcelli D;Di Donato M;Malavazos A;Capogrossi MC;Menicanti L;Martelli F
2型糖尿病患者缺血性心力衰竭（HF）相关的发病率和死亡率增加，需要更深入地了解其发病机制。鉴于microRNA（miRNAs）在HF中的意义，我们研究了它们的调节和潜在作用。在10例糖尿病HF（D-HF）和19例非糖尿病HF（ND-HF）非终末期扩张型缺血性心肌病患者的左心室活检组织中测定了miRNA表达谱。将HF组相互比较，并与16名匹配的非糖尿病非HF对照受试者进行比较。与对照受试者相比，D-HF和/或ND-HF患者中共有17种miRNA被调节。miR-216 a在D-HF和ND-HF患者中均强烈增加，与左心室射血分数呈负相关。当比较D-HF和ND-HF患者时，六种miRNA表达不同：miR-34 b、miR-34 c、miR-199 b、miR-210、miR-650和miR-223。其调制目标的生物信息学分析显示心脏功能障碍和HF类别的富集。此外，缺氧诱导因子途径被激活的非梗死，重要的心肌D-HF与ND-HF患者相比，表明缺氧反应机制失调。因此，在体外培养的心肌细胞和内皮细胞中，miR-199 a、miR-199 b和miR-210受到缺氧和高糖的调节。总之，这些发现显示了HF中miRNA的失调，阐明了区分糖尿病患者的特定疾病机制。
Increased morbidity and mortality associated with ischemic heart failure (HF) in type 2 diabetic patients requires a deeper understanding of the underpinning pathogenetic mechanisms. Given the implication of microRNAs (miRNAs) in HF, we investigated their regulation and potential role. miRNA expression profiles were measured in left ventricle biopsies from 10 diabetic HF (D-HF) and 19 nondiabetic HF (ND-HF) patients affected by non–end stage dilated ischemic cardiomyopathy. The HF groups were compared with each other and with 16 matched nondiabetic, non-HF control subjects. A total of 17 miRNAs were modulated in D-HF and/or ND-HF patients when compared with control subjects. miR-216a, strongly increased in both D-HF and ND-HF patients, negatively correlated with left ventricular ejection fraction. Six miRNAs were differently expressed when comparing D-HF and ND-HF patients: miR-34b, miR-34c, miR-199b, miR-210, miR-650, and miR-223. Bioinformatic analysis of their modulated targets showed the enrichment of cardiac dysfunctions and HF categories. Moreover, the hypoxia-inducible factor pathway was activated in the noninfarcted, vital myocardium of D-HF compared with ND-HF patients, indicating a dysregulation of the hypoxia response mechanisms. Accordingly, miR-199a, miR-199b, and miR-210 were modulated by hypoxia and high glucose in cardiomyocytes and endothelial cells cultured in vitro. In conclusion, these findings show a dysregulation of miRNAs in HF, shedding light on the specific disease mechanisms differentiating diabetic patients.
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糖尿病并发症：microRNA观点。
影响因子：
7.7
作者：
Kantharidis P;Wang B;Carew RM;Lan HY
通讯作者：
Lan HY
影响因子：
37.8
作者：
Hu S;Huang M;Li Z;Jia F;Ghosh Z;Lijkwan MA;Fasanaro P;Sun N;Wang X;Martelli F;Robbins RC;Wu JC
通讯作者：
Wu JC
影响因子：
1.9
作者：
Castelvecchio S;Menicanti L;Donato MD
通讯作者：
Donato MD
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
4.8
作者：
Fasanaro, Pasquale;D'Alessandra, Yuri;Martelli, Fabio
通讯作者：
Martelli, Fabio