ArticleProceedings of the National Academy of Sciences of the United States of America2023
Proteomics and phosphoproteomics of failing human left ventricle identifies dilated cardiomyopathy-associated phosphorylation of CTNNA3.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- A failing heart is a failing heart - until proteomics looks beyond etiology.Nature cardiovascular research · 2026Article
- Cardiac proteomic and phosphoproteomic profiling defines clinically relevant molecular subgroups in human heart failure.Nature cardiovascular research · 2026Article
- Kernelized approach enables explainable gene prioritizations for complex traits.bioRxiv : the preprint server for biology · 2026Article
- Consensus statement on mass spectrometry-based proteomic analysis of cardiac tissue.Nature cardiovascular research · 2026Article
- Phosphoproteomics distinguishes disease-specific mechanisms for human phospholamban cardiomyopathy reversible by RNA therapy.Signal transduction and targeted therapy · 2026Article
- Nonmuscle α-Actinin-4 Couples Sarcomere Function to Cardiac Remodeling.Circulation research · 2026Article
- Precision medicine and personalized nursing in cardiovascular disease: clinical applications and frontier developments.Frontiers in cardiovascular medicine · 2026Review
- Expanding the Recessive Spectrum of Dilated Cardiomyopathy: RNA-Level Validation of a HomozygousHuman mutation · 2026Article
- Intact Mass Profiling Reveals Phospho-Proteoforms of the Catenins (85-110 kDa) Regulated by Actomyosin Contractility.Angewandte Chemie (International ed. in English) · 2025Article
- Glyoxal is a superior fixative to formaldehyde in promoting antigenicity and structural integrity in murine cardiac tissues.Journal of molecular and cellular cardiology plus · 2025Article
- Filamin C dimerisation is regulated by HSPB7.Nature communications · 2025Article
- Cardiac Fibrosis in the Multi-Omics Era: Implications for Heart Failure.Circulation research · 2025Review
- Myocardial Proteome in Human Heart Failure With Preserved Ejection Fraction.Journal of the American Heart Association · 2025Article
- Integrated transcriptomic and regulatory RNA profiling reflects complex pathophysiology and uncovers a conserved gene signature in end stage heart failure.Journal of molecular and cellular cardiology plus · 2025Article
- Pyruvate dehydrogenase kinase 1 controls triacylglycerol hydrolysis in cardiomyocytes.bioRxiv : the preprint server for biology · 2025Article
- α-catenin phosphorylation is elevated during mitosis to resist apical rounding and epithelial barrier leak.Biology open · 2025Article
- Fortilin binds CTNNA3 and protects it against phosphorylation, ubiquitination, and proteasomal degradation to guard cells against apoptosis.Communications biology · 2025Article
- Proteomics of the heart.Physiological reviews · 2024Review
- Using Omics to Identify Novel Therapeutic Targets in Heart Failure.Circulation. Genomic and precision medicine · 2024Review
- CardiOmics signatures reveal therapeutically actionable targets and drugs for cardiovascular diseases.Heliyon · 2024Article
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
The prognosis and treatment outcomes of heart failure (HF) patients rely heavily on disease etiology, yet the majority of underlying signaling mechanisms are complex and not fully elucidated. Phosphorylation is a major point of protein regulation with rapid and profound effects on the function and activity of protein networks. Currently, there is a lack of comprehensive proteomic and phosphoproteomic studies examining cardiac tissue from HF patients with either dilated dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM). Here, we used a combined proteomic and phosphoproteomic approach to identify and quantify more than 5,000 total proteins with greater than 13,000 corresponding phosphorylation sites across explanted left ventricle (LV) tissue samples, including HF patients with DCM vs. nonfailing controls (NFC), and left ventricular infarct vs. noninfarct, and periinfarct vs. noninfarct regions of HF patients with ICM. Each pair-wise comparison revealed unique global proteomic and phosphoproteomic profiles with both shared and etiology-specific perturbations. With this approach, we identified a DCM-associated hyperphosphorylation cluster in the cardiomyocyte intercalated disc (ICD) protein, αT-catenin (CTNNA3). We demonstrate using both ex vivo isolated cardiomyocytes and in vivo using an AAV9-mediated overexpression mouse model, that CTNNA3 phosphorylation at these residues plays a key role in maintaining protein localization at the cardiomyocyte ICD to regulate conductance and cell-cell adhesion. Collectively, this integrative proteomic/phosphoproteomic approach identifies region- and etiology-associated signaling pathways in human HF and describes a role for CTNNA3 phosphorylation in the pathophysiology of DCM.
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Registered trials
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