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Article

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

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Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA
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Genomics, Proteomics, Bioinformatics and Systems Biology Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
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CardioVascular Center, Tufts Medical Center, Boston, MA 02111, USA
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Hypertrophic Cardiomyopathy Center, Tufts Medical Center, Boston, MA 02111, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Cheolju Lee
Int. J. Mol. Sci. 2021, 22(5), 2474; https://doi.org/10.3390/ijms22052474
Received: 4 February 2021 / Revised: 24 February 2021 / Accepted: 25 February 2021 / Published: 1 March 2021
(This article belongs to the Special Issue Genetic and Molecular Mechanisms of Hypertrophic Cardiomyopathy)
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. View Full-Text
Keywords: hypertrophic cardiomyopathy; proteomics; aptamer; cardiovascular disease; myectomy surgery hypertrophic cardiomyopathy; proteomics; aptamer; cardiovascular disease; myectomy surgery
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MDPI and ACS Style

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. https://doi.org/10.3390/ijms22052474

AMA Style

Larson A, Libermann TA, Bowditch H, Das G, Diakos N, Huggins GS, Rastegar H, Chen FY, Rowin EJ, Maron MS, Chin MT. Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation. International Journal of Molecular Sciences. 2021; 22(5):2474. https://doi.org/10.3390/ijms22052474

Chicago/Turabian Style

Larson, Amy, Towia A. Libermann, Heather Bowditch, Gaurav Das, Nikolaos Diakos, Gordon S. Huggins, Hassan Rastegar, Frederick Y. Chen, Ethan J. Rowin, Martin S. Maron, and Michael T. Chin 2021. "Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation" International Journal of Molecular Sciences 22, no. 5: 2474. https://doi.org/10.3390/ijms22052474

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