Osteopontin and LDLR are upregulated in hearts of sudden cardiac death victims with heart failure with preserved ejection fraction and diabetes mellitus
Mausam Patel, Mausam Patel; Rodriguez, Daniela; Yousefi, Keyvan; John-Williams, Krista; Mendez, Armando J.; Goldberg, Ronald B.; Lymperopoulos, Anastasios; Tamariz, Leonardo J.; Goldberger, Jeffrey J.; Myerburg, Robert J.; Junttila, Juhani; Shehadeh, Lina A. (2020-11-30)
Patel M, Rodriguez D, Yousefi K, John-Williams K, Mendez AJ, Goldberg RB, Lymperopoulos A, Tamariz LJ, Goldberger JJ, Myerburg RJ, Junttila J and Shehadeh LA (2020) Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus. Front. Cardiovasc. Med. 7:610282. doi: 10.3389/fcvm.2020.610282
© 2020 Patel, Rodriguez, Yousefi, John-Williams, Mendez, Goldberg, Lymperopoulos, Tamariz, Goldberger, Myerburg, Junttila and Shehadeh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe202102185325
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Abstract
Background: Diabetes mellitus (DM) is associated with increased risk of sudden cardiac death (SCD), particularly in patients with heart failure with preserved ejection fraction (HFpEF). However, there are no known biomarkers in the population with DM and HFpEF to predict SCD risk.
Objectives: This study was designed to test the hypothesis that osteopontin (OPN) and some proteins previously correlated with OPN, low-density lipoprotein receptor (LDLR), dynamin 2 (DNM2), fibronectin-1 (FN1), and 2-oxoglutarate dehydrogenase-like (OGDHL), are potential risk markers for SCD, and may reflect modifiable molecular pathways in patients with DM and HFpEF.
Methods: Heart tissues were obtained at autopsy from 9 SCD victims with DM and HFpEF and 10 age and gender-matched accidental death control subjects from a Finnish SCD registry and analyzed for the expression of OPN and correlated proteins, including LDLR, DNM2, FN1, and OGDHL by immunohistochemistry.
Results: We observed a significant upregulation in the expression of OPN, LDLR, and FN1, and a marked downregulation of DNM2 in heart tissues of SCD victims with DM and HFpEF as compared to control subjects (p < 0.01).
Conclusions: The dysregulated protein expression of OPN, LDLR, FN1, and DNM2 in patients with DM and HFpEF who experienced SCD provides novel potential modifiable molecular pathways that may be implicated in the pathogenesis of SCD in these patients. Since secreted OPN and soluble LDLR can be measured in plasma, these results support the value of further prospective studies to assess the predictive value of these plasma biomarkers and to determine whether tuning expression levels of OPN and LDLR alters SCD risk in patients with DM and HFpEF.
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