HSP60 knockdown exerts differential response in endothelial cells and monocyte derived macrophages during atherogenic transformation

Abstract Ectopic expression of HSP60 in vascular cells is known to activate auto-immune response that is critical to atherogenic initiation. However, the pathogenic relevance of the aberrant HSP60 upregulation in intracellular signaling pathways associated with atherogenic consequences in vascular c...

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Autores principales:	Kavita Shirsath, Apeksha Joshi, Aliasgar Vohra, Ranjitsinh Devkar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/32730b46f4f44cc0a8ba2432f8754372
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spelling	oai:doaj.org-article:32730b46f4f44cc0a8ba2432f87543722021-12-02T14:12:09ZHSP60 knockdown exerts differential response in endothelial cells and monocyte derived macrophages during atherogenic transformation10.1038/s41598-020-79927-22045-2322https://doaj.org/article/32730b46f4f44cc0a8ba2432f87543722021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79927-2https://doaj.org/toc/2045-2322Abstract Ectopic expression of HSP60 in vascular cells is known to activate auto-immune response that is critical to atherogenic initiation. However, the pathogenic relevance of the aberrant HSP60 upregulation in intracellular signaling pathways associated with atherogenic consequences in vascular cells remains unclear. The aim of the present study was to determine the role of endogenous HSP60 in atherogenic transformation of endothelial cells and macrophages. After generating primary evidence of oxidized low density lipoprotein (OxLDL) induced HSP60 upregulation in human umbilical vein endothelial cells (HUVEC), its physiological relevance in high fat high fructose (HFHF) induced early atherogenic remodelling was investigated in C57BL/6J mice. Prominent HSP60 expression was recorded in tunica intima and media of thoracic aorta that showed hypertrophy, lumen dilation, elastin fragmentation and collagen deposition. Further, HSP60 overexpression was found to be prerequisite for its surface localization and secretion in HUVEC. eNOS downregulation and MCP-1, VCAM-1 and ICAM-1 upregulation with subsequent macrophage accumulation provided compelling evidences on HFHF induced endothelial dysfunction and activation that were also observed in OxLDL treated- and HSP60 overexpressing-HUVEC. OxLDL induced concomitant reduction in NO production and monocyte adhesion were prevented by HSP60 knockdown, implying towards HSP60 mediated possible regulation of the said genes. OxLDL induced HSP60 upregulation and secretion was also recorded in THP-1 derived macrophages (TDMs). HSP60 knockdown in TDMs accounted for higher OxLDL accumulation that correlated with altered scavenger receptors (SR-A1, CD36 and SR-B1) expression further culminating in M1 polarization. Collectively, the results highlight HSP60 upregulation as a critical vascular alteration that exerts differential regulatory role in atherogenic transformation of endothelial cells and macrophages.Kavita ShirsathApeksha JoshiAliasgar VohraRanjitsinh DevkarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kavita Shirsath Apeksha Joshi Aliasgar Vohra Ranjitsinh Devkar HSP60 knockdown exerts differential response in endothelial cells and monocyte derived macrophages during atherogenic transformation
description	Abstract Ectopic expression of HSP60 in vascular cells is known to activate auto-immune response that is critical to atherogenic initiation. However, the pathogenic relevance of the aberrant HSP60 upregulation in intracellular signaling pathways associated with atherogenic consequences in vascular cells remains unclear. The aim of the present study was to determine the role of endogenous HSP60 in atherogenic transformation of endothelial cells and macrophages. After generating primary evidence of oxidized low density lipoprotein (OxLDL) induced HSP60 upregulation in human umbilical vein endothelial cells (HUVEC), its physiological relevance in high fat high fructose (HFHF) induced early atherogenic remodelling was investigated in C57BL/6J mice. Prominent HSP60 expression was recorded in tunica intima and media of thoracic aorta that showed hypertrophy, lumen dilation, elastin fragmentation and collagen deposition. Further, HSP60 overexpression was found to be prerequisite for its surface localization and secretion in HUVEC. eNOS downregulation and MCP-1, VCAM-1 and ICAM-1 upregulation with subsequent macrophage accumulation provided compelling evidences on HFHF induced endothelial dysfunction and activation that were also observed in OxLDL treated- and HSP60 overexpressing-HUVEC. OxLDL induced concomitant reduction in NO production and monocyte adhesion were prevented by HSP60 knockdown, implying towards HSP60 mediated possible regulation of the said genes. OxLDL induced HSP60 upregulation and secretion was also recorded in THP-1 derived macrophages (TDMs). HSP60 knockdown in TDMs accounted for higher OxLDL accumulation that correlated with altered scavenger receptors (SR-A1, CD36 and SR-B1) expression further culminating in M1 polarization. Collectively, the results highlight HSP60 upregulation as a critical vascular alteration that exerts differential regulatory role in atherogenic transformation of endothelial cells and macrophages.
format	article
author	Kavita Shirsath Apeksha Joshi Aliasgar Vohra Ranjitsinh Devkar
author_facet	Kavita Shirsath Apeksha Joshi Aliasgar Vohra Ranjitsinh Devkar
author_sort	Kavita Shirsath
title	HSP60 knockdown exerts differential response in endothelial cells and monocyte derived macrophages during atherogenic transformation
title_short	HSP60 knockdown exerts differential response in endothelial cells and monocyte derived macrophages during atherogenic transformation
title_full	HSP60 knockdown exerts differential response in endothelial cells and monocyte derived macrophages during atherogenic transformation
title_fullStr	HSP60 knockdown exerts differential response in endothelial cells and monocyte derived macrophages during atherogenic transformation
title_full_unstemmed	HSP60 knockdown exerts differential response in endothelial cells and monocyte derived macrophages during atherogenic transformation
title_sort	hsp60 knockdown exerts differential response in endothelial cells and monocyte derived macrophages during atherogenic transformation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/32730b46f4f44cc0a8ba2432f8754372
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HSP60 knockdown exerts differential response in endothelial cells and monocyte derived macrophages during atherogenic transformation

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