Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus
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 st...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2020.610282/full |
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| author | Mausam Patel Daniela Rodriguez Keyvan Yousefi Keyvan Yousefi Keyvan Yousefi Krista John-Williams Armando J. Mendez Ronald B. Goldberg Anastasios Lymperopoulos Leonardo J. Tamariz Leonardo J. Tamariz Jeffrey J. Goldberger Robert J. Myerburg Robert J. Myerburg Juhani Junttila Lina A. Shehadeh Lina A. Shehadeh Lina A. Shehadeh |
| author_facet | Mausam Patel Daniela Rodriguez Keyvan Yousefi Keyvan Yousefi Keyvan Yousefi Krista John-Williams Armando J. Mendez Ronald B. Goldberg Anastasios Lymperopoulos Leonardo J. Tamariz Leonardo J. Tamariz Jeffrey J. Goldberger Robert J. Myerburg Robert J. Myerburg Juhani Junttila Lina A. Shehadeh Lina A. Shehadeh Lina A. Shehadeh |
| author_sort | Mausam Patel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T13:38:51Z |
| format | Article |
| id | doaj.art-b76e8fc3ec4142199460b3d0c6c4a50a |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-13T13:38:51Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-b76e8fc3ec4142199460b3d0c6c4a50a2022-12-21T23:43:38ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2020-11-01710.3389/fcvm.2020.610282610282Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes MellitusMausam Patel0Daniela Rodriguez1Keyvan Yousefi2Keyvan Yousefi3Keyvan Yousefi4Krista John-Williams5Armando J. Mendez6Ronald B. Goldberg7Anastasios Lymperopoulos8Leonardo J. Tamariz9Leonardo J. Tamariz10Jeffrey J. Goldberger11Robert J. Myerburg12Robert J. Myerburg13Juhani Junttila14Lina A. Shehadeh15Lina A. Shehadeh16Lina A. Shehadeh17Division of Cardiology, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesInterdisciplinary Stem Cell Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesDivision of Cardiology, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesInterdisciplinary Stem Cell Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesDepartment of Molecular and Cellular Pharmacology, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesDivision of Cardiology, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesDivision of Endocrinolgy, Diabetes and Metabolism, Department of Medicine, The Diabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesDivision of Endocrinolgy, Diabetes and Metabolism, Department of Medicine, The Diabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesDepartment of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, United StatesDivision of Cardiology, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesMiami VA Healthcare System, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesDivision of Cardiology, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesDivision of Cardiology, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesAmerican Heart Association, Dallas, TX, United StatesMedical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, FinlandDivision of Cardiology, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesInterdisciplinary Stem Cell Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesPeggy and Harold Katz Family Drug Discovery Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United StatesBackground: 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.https://www.frontiersin.org/articles/10.3389/fcvm.2020.610282/fullsudden cardiac death (SCD)diabetes mellilusosteopontin (OPN)LDLRHFpEF—heart failure with preserved ejection fraction |
| spellingShingle | Mausam Patel Daniela Rodriguez Keyvan Yousefi Keyvan Yousefi Keyvan Yousefi Krista John-Williams Armando J. Mendez Ronald B. Goldberg Anastasios Lymperopoulos Leonardo J. Tamariz Leonardo J. Tamariz Jeffrey J. Goldberger Robert J. Myerburg Robert J. Myerburg Juhani Junttila Lina A. Shehadeh Lina A. Shehadeh Lina A. Shehadeh Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus Frontiers in Cardiovascular Medicine sudden cardiac death (SCD) diabetes mellilus osteopontin (OPN) LDLR HFpEF—heart failure with preserved ejection fraction |
| title | Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus |
| title_full | Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus |
| title_fullStr | Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus |
| title_full_unstemmed | Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus |
| title_short | Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus |
| title_sort | osteopontin and ldlr are upregulated in hearts of sudden cardiac death victims with heart failure with preserved ejection fraction and diabetes mellitus |
| topic | sudden cardiac death (SCD) diabetes mellilus osteopontin (OPN) LDLR HFpEF—heart failure with preserved ejection fraction |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2020.610282/full |
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