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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

Osteopontin and LDLR are upregulated in hearts of sudden cardiac death victims with heart failure with preserved ejection fraction and diabetes mellitus

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Author: Mausam Patel, Mausam Patel1; Rodriguez, Daniela2; Yousefi, Keyvan1,2,3;
Organizations: 1Division of Cardiology, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States
2Interdisciplinary Stem Cell Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States
3Department of Molecular and Cellular Pharmacology, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States
4Division of Endocrinolgy, Diabetes and Metabolism, Department of Medicine, The Diabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States
5Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, United States
6Miami VA Healthcare System, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States
7American Heart Association, Dallas, TX, United States
8Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
9Peggy and Harold Katz Family Drug Discovery Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 5.6 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe202102185325
Language: English
Published: Frontiers Media, 2020
Publish Date: 2021-02-18
Description:

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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Series: Frontiers in cardiovascular medicine
ISSN: 2297-055X
ISSN-E: 2297-055X
ISSN-L: 2297-055X
Volume: 7
Article number: 610282
DOI: 10.3389/fcvm.2020.610282
OADOI: https://oadoi.org/10.3389/fcvm.2020.610282
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Subjects:
HFpEF-heart failure with preserved ejection fraction
LDLR
diabetes mellilus
osteopontin (OPN)
sudden cardiac death (SCD)
Article
Funding: This work was supported by the following grants to LS: National Institute of Health (1R01HL140468) and the Miami Heart Research Institute. KY was a recipient of AHA predoctoral fellowship (18PRE33960070). RM was supported in part by the American Heart Association Chair in Cardiovascular Research at the University of Miami. JJ was supported by grants from Finnish Foundation for Cardiovascular Research, Sigrid Juselius Foundation, and Jane and Aatos Erkko Foundation.
Copyright information: © 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/