Variable Effects Of LDL Subclasses Of Cholesterol On Endothelial Nitric Oxide/Peroxynitrite Balance – The Risks And Clinical Implications For Cardiovascular Disease

Jiangzhou Hua , Tadeusz Malinski Nanomedical Research Laboratory, Ohio University, Athens, OH, USACorrespondence: Tadeusz MalinskiNanomedical Research Laboratory, Biochemistry Research Facility, Ohio University, 350 West State Street, Athens, OH 45701, USATel/fax +1 740 597 1247Email malinski@ohio.e...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hua J, Malinski T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	low density lipoprotein nitric oxide endothelium peroxynitrite cell adhesion Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8d656a0082344a20abdf881b9fe15400
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8d656a0082344a20abdf881b9fe15400
record_format	dspace
spelling	oai:doaj.org-article:8d656a0082344a20abdf881b9fe154002021-12-02T08:18:22ZVariable Effects Of LDL Subclasses Of Cholesterol On Endothelial Nitric Oxide/Peroxynitrite Balance – The Risks And Clinical Implications For Cardiovascular Disease1178-2013https://doaj.org/article/8d656a0082344a20abdf881b9fe154002019-11-01T00:00:00Zhttps://www.dovepress.com/variable-effects-of-ldl-subclasses-of-cholesterol-on-endothelial-nitri-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jiangzhou Hua , Tadeusz Malinski Nanomedical Research Laboratory, Ohio University, Athens, OH, USACorrespondence: Tadeusz MalinskiNanomedical Research Laboratory, Biochemistry Research Facility, Ohio University, 350 West State Street, Athens, OH 45701, USATel/fax +1 740 597 1247Email malinski@ohio.eduBackground: Elevated levels of low density lipoprotein (LDL), “bad cholesterol”, is not an accurate indicator of coronary disease. About 75% of patients with heart attacks have cholesterol levels that do not indicate a high risk for a cardiovascular event. LDL is comprised of three subclasses, with particles of different size and density. We used nanomedical systems to elucidate the noxious effects of LDL subclasses on endothelium.Experimental: Nanosensors were employed to measure the concentrations of nitric oxide (NO) and peroxynitrite (ONOO−) stimulated by LDL subclasses in HUVECs. N-LDL and ox-LDL (subclass A: 1.016–1.019 g/mL, subclass I: 1.024–1.029 g/mL, and subclass B: 1.034–1.053 g/mL) stimulated NO and ONOO− release. The concentrations ratio of (NO)/(ONOO−) was used to evaluate the noxious effects of the subclasses on endothelium.Results: In HUVECs, the (NO)/(ONOO−) ratio for normal endothelium is about 5, but shifts to 2.7±0.4, 0.5±0.1, and 0.9±0.1 for subclasses A, B, and I, respectively. Ratios below 1.0 indicate an imbalance between NO and ONOO−, affecting endothelial function. LDL of 50% B and 50% I produced the most severe imbalance (0.45±0.04), whereas LDL of 60% A, 20% B, and 20% I had the most favorable balance of 5.66±0.69. Subclass B significantly elevated the adhesion of molecules and monocytes. The noxious effect was significantly higher for ox-LDL than n-LDL.Conclusion: Subclass B of “bad cholesterol” is the most damaging to endothelial function and can contribute to the development of atherosclerosis. Contrary to the current national guidelines, this study suggests that it’s not the total LDL, rather it is the concentration of subclass B in relation to subclasses A and/or I, that should be used for diagnosis of atherosclerosis and the risk of heart attack. By utilizing specific pharmacological therapy to address the concentration of subclass B, there is a potential to significantly reduce the risk of heart attack and atherosclerosis.Keywords: low density lipoprotein, nitric oxide, endothelium, peroxynitrite, cell adhesionHua JMalinski TDove Medical Pressarticlelow density lipoproteinnitric oxideendotheliumperoxynitritecell adhesionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 8973-8987 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	low density lipoprotein nitric oxide endothelium peroxynitrite cell adhesion Medicine (General) R5-920
spellingShingle	low density lipoprotein nitric oxide endothelium peroxynitrite cell adhesion Medicine (General) R5-920 Hua J Malinski T Variable Effects Of LDL Subclasses Of Cholesterol On Endothelial Nitric Oxide/Peroxynitrite Balance – The Risks And Clinical Implications For Cardiovascular Disease
description	Jiangzhou Hua , Tadeusz Malinski Nanomedical Research Laboratory, Ohio University, Athens, OH, USACorrespondence: Tadeusz MalinskiNanomedical Research Laboratory, Biochemistry Research Facility, Ohio University, 350 West State Street, Athens, OH 45701, USATel/fax +1 740 597 1247Email malinski@ohio.eduBackground: Elevated levels of low density lipoprotein (LDL), “bad cholesterol”, is not an accurate indicator of coronary disease. About 75% of patients with heart attacks have cholesterol levels that do not indicate a high risk for a cardiovascular event. LDL is comprised of three subclasses, with particles of different size and density. We used nanomedical systems to elucidate the noxious effects of LDL subclasses on endothelium.Experimental: Nanosensors were employed to measure the concentrations of nitric oxide (NO) and peroxynitrite (ONOO−) stimulated by LDL subclasses in HUVECs. N-LDL and ox-LDL (subclass A: 1.016–1.019 g/mL, subclass I: 1.024–1.029 g/mL, and subclass B: 1.034–1.053 g/mL) stimulated NO and ONOO− release. The concentrations ratio of (NO)/(ONOO−) was used to evaluate the noxious effects of the subclasses on endothelium.Results: In HUVECs, the (NO)/(ONOO−) ratio for normal endothelium is about 5, but shifts to 2.7±0.4, 0.5±0.1, and 0.9±0.1 for subclasses A, B, and I, respectively. Ratios below 1.0 indicate an imbalance between NO and ONOO−, affecting endothelial function. LDL of 50% B and 50% I produced the most severe imbalance (0.45±0.04), whereas LDL of 60% A, 20% B, and 20% I had the most favorable balance of 5.66±0.69. Subclass B significantly elevated the adhesion of molecules and monocytes. The noxious effect was significantly higher for ox-LDL than n-LDL.Conclusion: Subclass B of “bad cholesterol” is the most damaging to endothelial function and can contribute to the development of atherosclerosis. Contrary to the current national guidelines, this study suggests that it’s not the total LDL, rather it is the concentration of subclass B in relation to subclasses A and/or I, that should be used for diagnosis of atherosclerosis and the risk of heart attack. By utilizing specific pharmacological therapy to address the concentration of subclass B, there is a potential to significantly reduce the risk of heart attack and atherosclerosis.Keywords: low density lipoprotein, nitric oxide, endothelium, peroxynitrite, cell adhesion
format	article
author	Hua J Malinski T
author_facet	Hua J Malinski T
author_sort	Hua J
title	Variable Effects Of LDL Subclasses Of Cholesterol On Endothelial Nitric Oxide/Peroxynitrite Balance – The Risks And Clinical Implications For Cardiovascular Disease
title_short	Variable Effects Of LDL Subclasses Of Cholesterol On Endothelial Nitric Oxide/Peroxynitrite Balance – The Risks And Clinical Implications For Cardiovascular Disease
title_full	Variable Effects Of LDL Subclasses Of Cholesterol On Endothelial Nitric Oxide/Peroxynitrite Balance – The Risks And Clinical Implications For Cardiovascular Disease
title_fullStr	Variable Effects Of LDL Subclasses Of Cholesterol On Endothelial Nitric Oxide/Peroxynitrite Balance – The Risks And Clinical Implications For Cardiovascular Disease
title_full_unstemmed	Variable Effects Of LDL Subclasses Of Cholesterol On Endothelial Nitric Oxide/Peroxynitrite Balance – The Risks And Clinical Implications For Cardiovascular Disease
title_sort	variable effects of ldl subclasses of cholesterol on endothelial nitric oxide/peroxynitrite balance – the risks and clinical implications for cardiovascular disease
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/8d656a0082344a20abdf881b9fe15400
work_keys_str_mv	AT huaj variableeffectsofldlsubclassesofcholesterolonendothelialnitricoxideperoxynitritebalancetherisksandclinicalimplicationsforcardiovasculardisease AT malinskit variableeffectsofldlsubclassesofcholesterolonendothelialnitricoxideperoxynitritebalancetherisksandclinicalimplicationsforcardiovasculardisease
_version_	1718398555739127808

Variable Effects Of LDL Subclasses Of Cholesterol On Endothelial Nitric Oxide/Peroxynitrite Balance – The Risks And Clinical Implications For Cardiovascular Disease

Ejemplares similares