Dataset Information

Proteomic profiling of a large cohort of HCM patients: genotype-specific protein changes

ABSTRACT: Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric left ventricular (LV) hypertrophy and diastolic dysfunction, which leads to LV outflow tract obstruction (LVOTO) in the majority of cases. Mutations in genes encoding sarcomeric proteins cause HCM and are identified in more than half of the patients (sarcomere-mutation positive, SMP). Currently, more than 1500 HCM-causing mutations are known. Approximately 80% of mutations are located in the MYH7 and MYBPC3 genes, encoding for the thick filament proteins β-myosin heavy chain (β-MHC) and cardiac myosin-binding protein C (cMyBP-C), respectively. Less frequent are mutations in the TNNT2 and TNNI3 genes, encoding for the thin filament proteins cardiac troponin T (cTnT) and I (cTnI). Here, we applied an unbiased proteomics approach in a large number of myectomy samples from a clinically well-characterized HCM patient group to define HCM-specific derailments as well as genotype-specific changes at protein level. Our study shows that the downregulation of metabolic pathways and the upregulation of extracellular matrix proteins are the most prominent HCM-specific disease characteristics that are present in all samples independent of their genotype.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Sander Piersma

LAB HEAD: Connie Ramona Jimenez

PROVIDER: PXD012467 | Pride | 2021-01-14

REPOSITORIES: Pride

ACCESS DATA

Publications

Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy.

Schuldt Maike M Pei Jiayi J Harakalova Magdalena M Dorsch Larissa M LM Schlossarek Saskia S Mokry Michal M Knol Jaco C JC Pham Thang V TV Schelfhorst Tim T Piersma Sander R SR Dos Remedios Cris C Dalinghaus Michiel M Michels Michelle M Asselbergs Folkert W FW Moutin Marie-Jo MJ Carrier Lucie L Jimenez Connie R CR van der Velden Jolanda J Kuster Diederik W D DWD

Circulation. Heart failure 20210112 1

<h4>Background</h4>Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCM<sub>SMP</sub>), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCM<sub>SMN</sub>). Genotype-specific differences have been reported in cardiac function. Moreover, HCM<sub>SMN</sub> patients have later disease onset and a better prognosis than HCM<sub>SMP</ ...[more]

PMID: 33430602

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Dataset Information

Proteomic profiling of a large cohort of HCM patients: genotype-specific protein changes

Publications

Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy.

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