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

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 bioma...

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Autores principales: Larson, Amy, Libermann, Towia A., Bowditch, Heather, Das, Gaurav, Diakos, Nikolaos, Huggins, Gordon S., Rastegar, Hassan, Chen, Frederick Y., Rowin, Ethan J., Maron, Martin S., Chin, Michael T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957543/
https://www.ncbi.nlm.nih.gov/pubmed/33804404
http://dx.doi.org/10.3390/ijms22052474
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author Larson, Amy
Libermann, Towia A.
Bowditch, Heather
Das, Gaurav
Diakos, Nikolaos
Huggins, Gordon S.
Rastegar, Hassan
Chen, Frederick Y.
Rowin, Ethan J.
Maron, Martin S.
Chin, Michael T.
author_facet Larson, Amy
Libermann, Towia A.
Bowditch, Heather
Das, Gaurav
Diakos, Nikolaos
Huggins, Gordon S.
Rastegar, Hassan
Chen, Frederick Y.
Rowin, Ethan J.
Maron, Martin S.
Chin, Michael T.
author_sort Larson, Amy
collection PubMed
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.
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spelling pubmed-79575432021-03-16 Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation Larson, Amy Libermann, Towia A. Bowditch, Heather Das, Gaurav Diakos, Nikolaos Huggins, Gordon S. Rastegar, Hassan Chen, Frederick Y. Rowin, Ethan J. Maron, Martin S. Chin, Michael T. Int J Mol Sci Article 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. MDPI 2021-03-01 /pmc/articles/PMC7957543/ /pubmed/33804404 http://dx.doi.org/10.3390/ijms22052474 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Larson, Amy
Libermann, Towia A.
Bowditch, Heather
Das, Gaurav
Diakos, Nikolaos
Huggins, Gordon S.
Rastegar, Hassan
Chen, Frederick Y.
Rowin, Ethan J.
Maron, Martin S.
Chin, Michael T.
Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation
title Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation
title_full Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation
title_fullStr Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation
title_full_unstemmed Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation
title_short Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation
title_sort plasma proteomic profiling in hypertrophic cardiomyopathy patients before and after surgical myectomy reveals post-procedural reduction in systemic inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957543/
https://www.ncbi.nlm.nih.gov/pubmed/33804404
http://dx.doi.org/10.3390/ijms22052474
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