The cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate COVID-19 outcomes in patients

Abstract Although metabolic syndrome (MetS) is linked to an elevated risk of cardiovascular disease (CVD), the cardiac-specific risk mechanism is unknown. Obesity, hypertension, and diabetes (all MetS components) are the most common form of CVD and represent risk factors for worse COVID-19 outcomes...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Olivia Ziegler, Nivedita Sriram, Vladimir Gelev, Denitsa Radeva, Kostadin Todorov, Jun Feng, Frank W. Selke, Simon C. Robson, Makoto Hiromura, Boian S. Alexandrov, Anny Usheva
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a44ca10268c34958baec7121327a4503
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a44ca10268c34958baec7121327a4503
record_format	dspace
spelling	oai:doaj.org-article:a44ca10268c34958baec7121327a45032021-12-02T17:13:17ZThe cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate COVID-19 outcomes in patients10.1038/s41598-021-99143-w2045-2322https://doaj.org/article/a44ca10268c34958baec7121327a45032021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99143-whttps://doaj.org/toc/2045-2322Abstract Although metabolic syndrome (MetS) is linked to an elevated risk of cardiovascular disease (CVD), the cardiac-specific risk mechanism is unknown. Obesity, hypertension, and diabetes (all MetS components) are the most common form of CVD and represent risk factors for worse COVID-19 outcomes compared to their non MetS peers. Here, we use obese Yorkshire pigs as a highly relevant animal model of human MetS, where pigs develop the hallmarks of human MetS and reproducibly mimics the myocardial pathophysiology in patients. Myocardium-specific mass spectroscopy-derived metabolomics, proteomics, and transcriptomics enabled the identity and quality of proteins and metabolites to be investigated in the myocardium to greater depth. Myocardium-specific deregulation of pro-inflammatory markers, propensity for arterial thrombosis, and platelet aggregation was revealed by computational analysis of differentially enriched pathways between MetS and control animals. While key components of the complement pathway and the immune response to viruses are under expressed, key N6-methyladenosin RNA methylation enzymes are largely overexpressed in MetS. Blood tests do not capture the entirety of metabolic changes that the myocardium undergoes, making this analysis of greater value than blood component analysis alone. Our findings create data associations to further characterize the MetS myocardium and disease vulnerability, emphasize the need for a multimodal therapeutic approach, and suggests a mechanism for observed worse outcomes in MetS patients with COVID-19 comorbidity.Olivia ZieglerNivedita SriramVladimir GelevDenitsa RadevaKostadin TodorovJun FengFrank W. SelkeSimon C. RobsonMakoto HiromuraBoian S. AlexandrovAnny UshevaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Olivia Ziegler Nivedita Sriram Vladimir Gelev Denitsa Radeva Kostadin Todorov Jun Feng Frank W. Selke Simon C. Robson Makoto Hiromura Boian S. Alexandrov Anny Usheva The cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate COVID-19 outcomes in patients
description	Abstract Although metabolic syndrome (MetS) is linked to an elevated risk of cardiovascular disease (CVD), the cardiac-specific risk mechanism is unknown. Obesity, hypertension, and diabetes (all MetS components) are the most common form of CVD and represent risk factors for worse COVID-19 outcomes compared to their non MetS peers. Here, we use obese Yorkshire pigs as a highly relevant animal model of human MetS, where pigs develop the hallmarks of human MetS and reproducibly mimics the myocardial pathophysiology in patients. Myocardium-specific mass spectroscopy-derived metabolomics, proteomics, and transcriptomics enabled the identity and quality of proteins and metabolites to be investigated in the myocardium to greater depth. Myocardium-specific deregulation of pro-inflammatory markers, propensity for arterial thrombosis, and platelet aggregation was revealed by computational analysis of differentially enriched pathways between MetS and control animals. While key components of the complement pathway and the immune response to viruses are under expressed, key N6-methyladenosin RNA methylation enzymes are largely overexpressed in MetS. Blood tests do not capture the entirety of metabolic changes that the myocardium undergoes, making this analysis of greater value than blood component analysis alone. Our findings create data associations to further characterize the MetS myocardium and disease vulnerability, emphasize the need for a multimodal therapeutic approach, and suggests a mechanism for observed worse outcomes in MetS patients with COVID-19 comorbidity.
format	article
author	Olivia Ziegler Nivedita Sriram Vladimir Gelev Denitsa Radeva Kostadin Todorov Jun Feng Frank W. Selke Simon C. Robson Makoto Hiromura Boian S. Alexandrov Anny Usheva
author_facet	Olivia Ziegler Nivedita Sriram Vladimir Gelev Denitsa Radeva Kostadin Todorov Jun Feng Frank W. Selke Simon C. Robson Makoto Hiromura Boian S. Alexandrov Anny Usheva
author_sort	Olivia Ziegler
title	The cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate COVID-19 outcomes in patients
title_short	The cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate COVID-19 outcomes in patients
title_full	The cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate COVID-19 outcomes in patients
title_fullStr	The cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate COVID-19 outcomes in patients
title_full_unstemmed	The cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate COVID-19 outcomes in patients
title_sort	cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate covid-19 outcomes in patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a44ca10268c34958baec7121327a4503
work_keys_str_mv	AT oliviaziegler thecardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT niveditasriram thecardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT vladimirgelev thecardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT denitsaradeva thecardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT kostadintodorov thecardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT junfeng thecardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT frankwselke thecardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT simoncrobson thecardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT makotohiromura thecardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT boiansalexandrov thecardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT annyusheva thecardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT oliviaziegler cardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT niveditasriram cardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT vladimirgelev cardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT denitsaradeva cardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT kostadintodorov cardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT junfeng cardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT frankwselke cardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT simoncrobson cardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT makotohiromura cardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT boiansalexandrov cardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients AT annyusheva cardiacmolecularsettingofmetabolicsyndromeinpigsrevealsdiseasesusceptibilityandsuggestsmechanismsthatexacerbatecovid19outcomesinpatients
_version_	1718381396429373440

The cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate COVID-19 outcomes in patients

Ejemplares similares