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Transcriptome Profiling of Surgical Myectomy Tissue from Patients with Hypertrophic Cardiomyopathy

ABSTRACT: Using a high-throughput gene expression profiling technology, we have been able to develop new hypotheses regarding the molecular pathogenic mechanisms of human hypertrophic cardiomyopathy (HCM). It is hoped that these hypotheses, among others generated by this data, will fuel future research endeavors that will uncover novel biomarkers, prognostic indicators, and therapeutic targets to improve our ability to diagnose, counsel, and treat patients with this highly heterogeneous and potentially life-threatening condition. Case-control study comparing the messenger RNA transcriptome of cardiac tissues from patients with hypertrophic cardiomyopathy to the transcriptome of control donor cardiac tissues.

ORGANISM(S): Homo sapiens

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PROVIDER: S-DIXA-D-1125 | biostudies-other |

REPOSITORIES: biostudies-other

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Transcriptome Profiling of Surgical Myectomy Tissue from Patients with Hypertrophic Cardiomyopathy

Project description:Using a high-throughput gene expression profiling technology, we have been able to develop new hypotheses regarding the molecular pathogenic mechanisms of human hypertrophic cardiomyopathy (HCM). It is hoped that these hypotheses, among others generated by this data, will fuel future research endeavors that will uncover novel biomarkers, prognostic indicators, and therapeutic targets to improve our ability to diagnose, counsel, and treat patients with this highly heterogeneous and potentially life-threatening condition.

2012-09-01 | GSE36961 | GEO

Transcriptome Profiling of Surgical Myectomy Tissue from Patients with Hypertrophic Cardiomyopathy

2012-09-01 | E-GEOD-36961 | biostudies-arrayexpress

MicroRNA Profiling of Surgical Myectomy Tissue from Patients with Hypertrophic Cardiomyopathy

Project description: Not available

| S-DIXA-D-1124 | biostudies-other

MicroRNA Profiling of Surgical Myectomy Tissue from Patients with Hypertrophic Cardiomyopathy

Project description:Using a high-throughput gene expression profiling technology, we have illuminated novel potential microRNA (miRNA) components of the molecular disease process underlying human hypertrophic cardiomyopathy (HCM). It is hoped that this will fuel future research endeavors that will eventually uncover the role miRNAs may play in the phenotypic heterogeneity of the disease, and thus, provide potential tools for identifying patients with benign versus malignant forms of the disease.

2012-09-01 | GSE36946 | GEO

MicroRNA Profiling of Surgical Myectomy Tissue from Patients with Hypertrophic Cardiomyopathy

2012-09-01 | E-GEOD-36946 | biostudies-arrayexpress

Plasma metabolomic profiling of hypertrophic cardiomyopathy patients before and after surgical myectomy suggests postoperative improvement in metabolic function.

Project description:BackgroundHypertrophic cardiomyopathy (HCM) is a common inherited heart disorder complicated by left ventricle outflow tract (LVOT) obstruction, which can be treated with surgical myectomy. To date, no reliable biomarkers for LVOT obstruction exist. We hypothesized that metabolomic biomarkers for LVOT obstruction may be detectable in plasma from HCM patients.MethodsWe conducted metabolomic profiling on plasma samples of 18 HCM patients before and after surgical myectomy, using a commercially available metabolomics platform.ResultsWe found that 215 metabolites were altered in the postoperative state (p-value < 0.05). 12 of these metabolites were notably significant after adjusting for multiple comparisons (q-value < 0.05), including bilirubin, PFOS, PFOA, 3,5-dichloro-2,6-dihydroxybenzoic acid, 2-hydroxylaurate, trigonelline and 6 unidentified compounds, which support improved organ metabolic function and increased lean soft tissue mass.ConclusionsThese findings suggest improved organ metabolic function after surgical relief of LVOT obstruction in HCM and further underscore the beneficial systemic effects of surgical myectomy.

| S-EPMC8714427 | biostudies-literature

Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation.

Project description:Left Ventricular Outflow Tract (LVOT) obstruction occurs in approximately 70% of Hypertrophic Cardiomyopathy (HCM) patients and currently requires imaging or invasive testing for diagnosis, sometimes in conjunction with provocative physiological or pharmaceutical stimuli. To identify potential biomarkers of LVOT obstruction, we performed proteomics profiling of 1305 plasma proteins in 12 HCM patients with documented LVOT obstruction, referred for surgical myectomy. Plasma was collected at the surgical preoperative visit, approximately one month prior to surgery and then at the post-surgical visit, approximately 3 months later. Proteomic profiles were generated using the aptamer-based SOMAscan assay. Principal Component Analysis using the highest statistically significant proteins separated all preoperative samples from all postoperative samples. Further analysis revealed a set of 25 proteins that distinguished the preoperative and postoperative states with a paired t-test p-value of <0.01. Ingenuity Pathway analysis facilitated the generation of protein interaction networks and the elucidation of key upstream regulators of differentially expressed proteins, such as interferon-γ, TGF-β1, and TNF. Biological pathways affected by surgery included organ inflammation, migration, and motility of leukocytes, fibrosis, vasculogenesis, angiogenesis, acute coronary events, endothelial proliferation, eicosanoid metabolism, calcium flux, apoptosis, and morphology of the cardiovascular system. Our results indicate that surgical relief of dynamic outflow tract obstruction in HCM patients is associated with unique alterations in plasma proteomic profiles that likely reflect improvement in organ inflammation and physiological function.

| S-EPMC7957543 | biostudies-literature

RNA-seq transcriptome profiling and whole exome sequencing data on Hypertrophic cardiomyopathy (HCM) patients

Project description:This study is to examine gene expression profiles in 18 HCM patients and compare them with those in 5 healthy controls. The hypothesis tested here is whether patient individual-level transcriptome data integrated with the human interactom can implicate the heterogenity of HCM phenotypes.In this study, we also analyze DNA whole-exome sequencing (WES) data from 18 patients.

2021-01-09 | GSE160997 | GEO

Comprehensive Proteomics Profiling Reveals Circulating Biomarkers of Hypertrophic Cardiomyopathy.

Project description:BackgroundHypertrophic cardiomyopathy (HCM) is caused by mutations in the genes coding for proteins essential in normal myocardial contraction. However, it remains unclear through which molecular pathways gene mutations mediate the development of HCM. The objectives were to determine plasma protein biomarkers of HCM and to reveal molecular pathways differentially regulated in HCM.MethodsWe conducted a multicenter case-control study of cases with HCM and controls with hypertensive left ventricular hypertrophy. We performed plasma proteomics profiling of 1681 proteins. We performed a sparse partial least squares discriminant analysis to develop a proteomics-based discrimination model with data from 1 institution (ie, the training set). We tested the discriminative ability in independent samples from the other institution (ie, the test set). As an exploratory analysis, we executed pathway analysis of significantly dysregulated proteins. Pathways with false discovery rate <0.05 were declared positive.ResultsThe study included 266 cases and 167 controls (n=308 in the training set; n=125 in the test set). Using the proteomics-based model derived from the training set, the area under the receiver operating characteristic curve was 0.89 (95% CI, 0.83-0.94) in the test set. Pathway analysis revealed that the Ras-MAPK (mitogen-activated protein kinase) pathway, along with its upstream and downstream pathways, was upregulated in HCM. Pathways involved in inflammation and fibrosis-for example, the TGF (transforming growth factor)-β pathway-were also upregulated.ConclusionsThis study serves as the largest-scale investigation with the most comprehensive proteomics profiling in HCM, revealing circulating biomarkers and exhibiting both novel (eg, Ras-MAPK) and known (eg, TGF-β) pathways differentially regulated in HCM.

| S-EPMC8292216 | biostudies-literature

Application of Proteomics Profiling for Biomarker Discovery in Hypertrophic Cardiomyopathy.

Project description:High-throughput proteomics profiling has never been applied to discover biomarkers in patients with hypertrophic cardiomyopathy (HCM). The objective was to identify plasma protein biomarkers that can distinguish HCM from controls. We performed a case-control study of patients with HCM (n?=?15) and controls (n?=?22). We carried out plasma proteomics profiling of 1129 proteins using the SOMAscan assay. We used the sparse partial least squares discriminant analysis to identify 50 most discriminant proteins. We also determined the area under the curve (AUC) of the receiver operating characteristic curve using the Monte Carlo cross validation with balanced subsampling. The average AUC was 0.94 (95% confidence interval, 0.82-1.00) and the discriminative accuracy was 89%. In HCM, 13 out of the 50 proteins correlated with troponin I and 12 with New York Heart Association class. Proteomics profiling can be used to elucidate protein biomarkers that distinguish HCM from controls.

| S-EPMC7102897 | biostudies-literature

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