Unknown,Transcriptomics,Genomics,Proteomics

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Fabio Martelli

PROVIDER: E-GEOD-26887 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

MicroRNA dysregulation in diabetic ischemic heart failure patients.

Greco Simona S Fasanaro Pasquale P Castelvecchio Serenella S D'Alessandra Yuri Y Arcelli Diego D Di Donato Marisa M Malavazos Alexis A Capogrossi Maurizio C MC Menicanti Lorenzo L Martelli Fabio F

Diabetes 20120316 6

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 co ...[more]

PMID: 22427379

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Project description:The cellular and molecular aspects of post-infarct left-ventricle remodeling in presence of type-2 diabetes is poorly understood. In this study we have addressed the cellular and molecular aspects underlying post-infarct left-ventricle remodeling in type 2 diabetic (T2DM) mice using genome-wide mRNA-sequencing. Myocardial infarction was induced by ligating left-anterior descending artery (LAD) in 12-14 month old T2DM and control mice. Cardiac MRI was performed at baseline, day 7 and 14 post-LAD ligation. Blood and tissue samples were collected for biochemical and immunohistochemical, molecular biology analysis after sacrification at day 7 and 14. Genome-wide mRNA sequencing analysis was performed from left-ventricular tissues collected at day 7 post-LAD ligation. Mitochondrial dynamics, Leukocyte recruitment and Collagen I deposition were analyzed using electron microscopy, fluorescent assisted cell sorting (FACS) and fourier-transform infra-red (FTIR) spectroscopy from left ventricular tissues collected at day 7 and 14 post-LAD ligation. Cardiac ejection fraction (EF) and stroke volume (SV) were significantly reduced along with increased mortality in T2DM compared to controls. Ingenuity pathway analyses of differentially expressed genes were enriched for mitochondrial dysfunction, TCA cycle and fatty acid oxidation. Additionally, upstream transcription factor analysis showed inhibition of PGC1a, PGC1b, ESRRA, ESRRB and TFAM in infarcted myocardium of T2DM mice. Electron microscopy analysis showed an altered mitochondrial dynamics and cardiomyocyte death in ischemic myocardium of T2DM mice. Leukocytes exhibited an altered phenotype in ischemic myocardium of T2DM mice. Neovascularization was impaired and collagen deposition was increased in ischemic myocardium of T2DM mice. We conclude that an altered mitochondrial dynamics, cell death modalities, leukocyte phenotype, neovascularization responses and fibrosis may contribute to an increased mortality after myocardial infarction in T2DM. Modulation of mitochondrial dynamics and cardiomyocyte cell death modalities may offer a novel therapeutic target.

Dataset Information

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

Publications

MicroRNA dysregulation in diabetic ischemic heart failure patients.

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