Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Amy Larson
ORCID logo ,
Towia A. Libermann
,
Heather Bowditch
,
Gaurav Das
,
Nikolaos Diakos
,
Gordon S. Huggins
,
Hassan Rastegar
,
Frederick Y. Chen
,
Ethan J. Rowin
,
Martin S. Maron
,
Michael T. Chin
* ORCID logo
Version 1 : Received: 4 February 2021 / Approved: 8 February 2021 / Online: 8 February 2021 (11:18:59 CET)

A peer-reviewed article of this Preprint also exists.

Larson, A.; Libermann, T.A.; Bowditch, H.; Das, G.; Diakos, N.; Huggins, G.S.; Rastegar, H.; Chen, F.Y.; Rowin, E.J.; Maron, M.S.; Chin, M.T. Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation. Int. J. Mol. Sci. 2021, 22, 2474. Larson, A.; Libermann, T.A.; Bowditch, H.; Das, G.; Diakos, N.; Huggins, G.S.; Rastegar, H.; Chen, F.Y.; Rowin, E.J.; Maron, M.S.; Chin, M.T. Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation. Int. J. Mol. Sci. 2021, 22, 2474.

Abstract

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 the differentially expressed proteins such as interferon-, TGF-1 and TNF. Biological pathways affected by the 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.

Keywords

Hypertrophic Cardiomyopathy; proteomics; aptamer; cardiovascular disease; myectomy surgery

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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