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

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. Overall design: 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.

糖尿病患者合并缺血性心力衰竭（post-ischemic heart failure, HF）时的发病率与死亡率升高，凸显了深入解析其潜在分子事件的迫切需求。事实上，针对糖尿病患者的心力衰竭有效治疗需要一套复杂策略，涵盖开发更优异的诊断与预后标志物，以及创新性药理学干预手段。本研究检测了伴或不伴2型糖尿病（Type 2 diabetes mellitus, T2DM）的心力衰竭患者心脏组织的全mRNA表达谱，并与非衰竭心脏对照样本进行对比。我们鉴定出心力衰竭患者相较于对照非衰竭心脏的差异表达基因，同时也鉴定出伴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。
研究整体设计：本研究纳入的样本取自接受外科心室修复手术的扩张型低动力性缺血性心肌病患者的存活非梗死区域（远程区域）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为：血糖<100 mg/dl，且糖化血红蛋白A1c（HbA1c）处于参考范围4.8%~6.0%。此外，本研究对心力衰竭患者按以下指标进行匹配：收缩末期容积（End Systolic Volume, ESV）、射血分数（Ejection fraction, LVEF）、年龄、性别、种族分布、吸烟习惯、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 GeneChips Human Gene 1.0 ST基因芯片对基因表达进行检测，所用总RNA提取自7例伴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例对照样本。