Transcriptome analysis of diabetic and non diabetic patients affected by post-ischemic heart failure

Increased morbidity and mortality associated with post-ischemic heart failure (HF) in diabetic patients underscore the need for a better understanding of the underlying molecular events. Indeed, effective HF therapy in diabetic patients requires a complex strategy encompassing the development of improved diagnostic and prognostic markers and innovative pharmacological approaches. Whole mRNAs expression was measured in the heart of patients with heart failure (HF) with or without concomitant Type 2 diabetes mellitus (T2DM) and compared it to control non-failing hearts. We identified distinct genes modulated in HF patients compared to controls, as well as to T2DM HF patients compared to not diabetic HF patients. Our study included left ventricle (LV) cardiac biopsies taken from the vital, non-infarcted zone (remote zone) derived from patients affected by dilated hypokinetic post-ischemic cardiomyopathy, undergoing surgical ventricular restoration procedure. Inclusion criteria for diabetic were: GLICEMIA: ≥126 mg/dl, previous T2DM diagnosis or anti-diabetic therapy, while for non diabetic: GLICEMIA: <100 mg/dl and HbA1c: n.v. 4.8-6.0%. Moreover, HF patients were matched for End Systolic Volume (ESV), Ejection fraction (LVEF), Age, Sex, Ethnic distribution, Smoke habits, Hypertension, Glomerular filtration rate (GFR), Body Mass Index (BMI). Genes expression was assessed by Affymetrix GeneChips Human Gene 1.0 ST array, using total RNA extracted from 7 T2DM HF patients, 12 non-T2DM HF patients and 5 controls.糖尿病患者合并梗死后心力衰竭（post-ischemic heart failure, HF）时，其发病率与死亡率均显著升高，这凸显了深入解析其潜在分子机制的迫切需求。诚然，针对糖尿病患者的心力衰竭有效治疗需要一套复杂策略，涵盖开发更优的诊断与预后标志物，以及创新的药理学干预手段。本研究对伴或不伴2型糖尿病（Type 2 diabetes mellitus, T2DM）的心力衰竭患者的心脏组织进行全mRNA表达谱检测，并将其与非衰竭对照心脏组织进行对比。我们分别鉴定出了心力衰竭患者相较于对照个体的差异表达基因，以及合并2型糖尿病的心力衰竭患者相较于非糖尿病心力衰竭患者的差异表达基因。本研究的样本取自接受外科心室重建术的扩张型动力减退性梗死后心肌病患者的存活非梗死区（又称远程区）的左心室（left ventricle, LV）心肌活检组织。糖尿病患者的纳入标准为：血糖≥126 mg/dl、既往确诊2型糖尿病或接受降糖治疗；非糖尿病患者的纳入标准则为：血糖<100 mg/dl且糖化血红蛋白（HbA1c）处于正常参考范围4.8%~6.0%。此外，本研究对心力衰竭患者的以下混杂因素进行了匹配对照：收缩末期容积（End Systolic Volume, ESV）、左心室射血分数（left ventricular ejection fraction, LVEF）、年龄、性别、种族分布、吸烟史、高血压病史、肾小球滤过率（Glomerular filtration rate, GFR）以及体质量指数（Body Mass Index, BMI）。本研究采用Affymetrix Human Gene 1.0 ST基因芯片平台检测基因表达水平，所用总RNA提取自7例合并2型糖尿病的心力衰竭患者、12例非糖尿病心力衰竭患者以及5例对照个体。