Transcriptome analysis of diabetic and non diabetic patients affected by post-ischemic heart failure
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE26887 | GEO | 2012/03/21
SECONDARY ACCESSION(S): PRJNA135947
REPOSITORIES: GEO
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Project description: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.
2012-03-21 | E-GEOD-26887 | biostudies-arrayexpress
Project description:Type 2 diabetes mellitus(T2DM)patients are a concern for dentists due to the lower success rate of healing period implant treatment. Here, we firstly calculated the success rate of in the healing period of diabetic and non-diabetic patients in the implant center of our hospital.Then we investigated the potential risk factors by proteomics analysis of 5 T2DM implant faliure patients in our implant center and compared the difference between high glucose induction study model and mesenchymal stem cell model from diabetic patients. The results suggested that the significantly higher implant failure rates in the T2DM group and the cell models derived from patients can be more comprehensive and accurate in reflecting the exact situation of BMSCs in patients with diabetes.
2021-11-02 | PXD016489 | Pride
Project description:Full Title: Transition from Compensated Hypertrophy to Systolic Heart Failure in the Spontaneously Hypertensive Rat: Structure, Function, and Transcript Analysis Gene expression changes and left ventricular remodeling associated with the transition to systolic heart failure (HF) were determined in the spontaneously hypertensive rat (SHR). By combining transcriptomics of left ventricles from six SHR with HF with changes in function and structure we aimed to better understand the molecular events underlying the onset of systolic HF compared to six age-matched, SHR with compensated hypertrophy. Left ventricle (LV) ejection fraction was depressed (82±4 to 52±3 %) in compensated vs. failing animals. Systolic blood pressure decreased and LV end-diastolic and systolic volume increased with HF. Failing SHR hearts also demonstrated increases in left and right ventricular mass relative to non-failing SHRs.  LV papillary muscle force development and shortening velocity decreased, β-adrenergic responsiveness was depressed, myocardial stiffness and myocardial fibrosis increased with HF relative to non-failing animals. Initial micro-array analysis revealed that 1,431 transcripts were differentially expressed with HF compared to non-failing SHR (p<0.05). Of the identified transcripts, lipopolysaccharide binding protein, the most highly expressed transcript with HF, was negatively correlated to myocardial force while elevated expression of the collagen cross-linking enzyme lysyl oxidase correlated positively with muscle stiffness. Besides these individual transcripts, gene set enrichment analysis (GSEA) identified multiple enriched pathways with HF, most prominent of the altered signaling pathways involved TGF-β and insulin signaling. GESA analysis additionally identified altered gene sets involving inflammation, oxidative stress, cell degradation and cell death, among others (all p<0.01). In contrast to diastolic HF where few transcripts are reported to be altered, our data indicate multiple genes and pathways involved in a variety of biological processes characterize the onset of systolic HF, consistent with many functional and structural changes present in the failing hypertensive heart. Comprehensive gene expression profiling of heart failure Rat model vs control.
2010-02-21 | E-GEOD-19210 | biostudies-arrayexpress
Project description:Full Title: Transition from Compensated Hypertrophy to Systolic Heart Failure in the Spontaneously Hypertensive Rat: Structure, Function, and Transcript Analysis Gene expression changes and left ventricular remodeling associated with the transition to systolic heart failure (HF) were determined in the spontaneously hypertensive rat (SHR). By combining transcriptomics of left ventricles from six SHR with HF with changes in function and structure we aimed to better understand the molecular events underlying the onset of systolic HF compared to six age-matched, SHR with compensated hypertrophy. Left ventricle (LV) ejection fraction was depressed (82±4 to 52±3 %) in compensated vs. failing animals. Systolic blood pressure decreased and LV end-diastolic and systolic volume increased with HF. Failing SHR hearts also demonstrated increases in left and right ventricular mass relative to non-failing SHRs. LV papillary muscle force development and shortening velocity decreased, β-adrenergic responsiveness was depressed, myocardial stiffness and myocardial fibrosis increased with HF relative to non-failing animals. Initial micro-array analysis revealed that 1,431 transcripts were differentially expressed with HF compared to non-failing SHR (p<0.05). Of the identified transcripts, lipopolysaccharide binding protein, the most highly expressed transcript with HF, was negatively correlated to myocardial force while elevated expression of the collagen cross-linking enzyme lysyl oxidase correlated positively with muscle stiffness. Besides these individual transcripts, gene set enrichment analysis (GSEA) identified multiple enriched pathways with HF, most prominent of the altered signaling pathways involved TGF-β and insulin signaling. GESA analysis additionally identified altered gene sets involving inflammation, oxidative stress, cell degradation and cell death, among others (all p<0.01). In contrast to diastolic HF where few transcripts are reported to be altered, our data indicate multiple genes and pathways involved in a variety of biological processes characterize the onset of systolic HF, consistent with many functional and structural changes present in the failing hypertensive heart.
2010-02-01 | GSE19210 | GEO
Project description:Oxidative stress plays a key role in development and progression of cardiovascular diseases and it is correlated with left ventricular dysfunction and heart failure (HF). Oxidative environments lead to the formation of intra- and intermolecular disulfide bonds, as well as to plethora of other reversible and irreversible oxidative amino acid modifications, affecting the functionality of the proteins. Here we report that heart failure due to ischemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) is correlated with increase in oxidative stress compared to non-failing control hearts, manifested through decreased GSH/GSSG ratio in failing heart tissue samples and adaptations of cardiac redox proteome which occur in correlation with two different heart pathologies.
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Project description:In response to heart failure (HF), the heart reacts by repressing adult genes and expressing fetal genes, thereby returning to a more fetal-like gene profile. To identify genes involved in this process, we carried out transcriptional analysis on murine hearts at different stages of development and adult mice with HF. Our screen identified 5-oxoprolinase (OPLAH), a member of the -Glutamyl cycle, that functions by scavenging 5-oxoproline. OPLAH depletion occurred as a result of cardiac injury, leading to elevated 5-oxoproline and oxidative stress, whereas OPLAH overexpression improved cardiac function after ischemic injury. In HF patients we observed elevated plasma 5-oxoproline levels, which were associated with a worse clinical outcome. Understanding and modulating fetal-like genes in the failing heart may lead to potential novel diagnostic, prognostic and therapeutic options in HF.
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Project description:AMP deaminase (AMPD) plays a crucial role in adenine nucleotide metabolism, and its upregulated activity contributes to diastolic dysfunction of the heart caused by type 2 diabetes mellitus (T2DM) via reduction of the adenine nucleotide pool. Here we examined the mechanism of AMPD upregulation by T2DM. The protein level of 90-kDa full-length AMPD3 was increased in whole myocardial lysates and in the sarcoplasmic reticulum (SR) fraction by 55% and 123%, respectively, in OLETF, a rat model of T2DM, compared to those in LETO, a non-diabetic control, though AMPD mRNA level was unchanged in OLETF. MicroRNA array analysis revealed downregulation (>50%) of 57 microRNAs in OLETF compared to those in LETO, among which miR-301b was predicted to interact with the 3’UTR of AMPD3 mRNA. The 90-kDa AMPD3 level was significantly increased by miR-301b inhibitor, but decreased by a miR-301b mimetic in H9c2 cells. A luciferase reporter assay indicated binding of miR-301b to the 3’UTR of AMPD3 mRNA. The results indicate that translational regulation by miR-301b mediates AMPD3 upregulation in the diabetic heart. Since ATP generated by SR-associated glycolytic enzymes contributes to Ca2+ uptake by SERCA2a, upregulated AMPD3 in the vicinity of the SR may be a therapeutic target for diabetic cardiomyopathy.
2017-05-24 | GSE99203 | GEO
Project description:AMP deaminase (AMPD) plays a crucial role in adenine nucleotide metabolism, and its upregulated activity contributes to diastolic dysfunction of the heart caused by type 2 diabetes mellitus (T2DM) via reduction of the adenine nucleotide pool. Here we examined the mechanism of AMPD upregulation by T2DM. The protein level of 90-kDa full-length AMPD3 was increased in whole myocardial lysates and in the sarcoplasmic reticulum (SR) fraction by 55% and 123%, respectively, in OLETF, a rat model of T2DM, compared to those in LETO, a non-diabetic control, though AMPD mRNA level was unchanged in OLETF. MicroRNA array analysis revealed downregulation (>50%) of 57 microRNAs in OLETF compared to those in LETO, among which miR-301b was predicted to interact with the 3’UTR of AMPD3 mRNA. The 90-kDa AMPD3 level was significantly increased by miR-301b inhibitor, but decreased by a miR-301b mimetic in H9c2 cells. A luciferase reporter assay indicated binding of miR-301b to the 3’UTR of AMPD3 mRNA. The results indicate that translational regulation by miR-301b mediates AMPD3 upregulation in the diabetic heart. Since ATP generated by SR-associated glycolytic enzymes contributes to Ca2+ uptake by SERCA2a, upregulated AMPD3 in the vicinity of the SR may be a therapeutic target for diabetic cardiomyopathy.
2017-05-31 | GSE99410 | GEO
Project description:Diabetic cardiomyopathy (DCM) is one of the major causes of heart failure in diabetic patients, but its pathogenesis remains unclear. Sodium glucose cotransporter 2 inhibitors (SGLT2i) can effectively reduce the risk of cardiovascular death and heart failure in DCM patients, but the underlying mechanism has not been elucidated. We established a DCM rat model followed by treatment with empagliflozin (EMPA) for 12 weeks. The proteomics of the myocardium in the rat model was performed to identify the potential targets and signaling pathways associated with the cardiovascular benefit of SGLT2i.
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