Role of hypothalamic-pituitary adrenal-axis, toll-like receptors, and macrophage polarization in pre-atherosclerotic changes induced by social isolation stress in mice

Abstract It has been well documented that chronic stress can induce atherosclerotic changes, however, the underlying mechanisms is yet to be established. In this regard, this study aimed to elucidate the relation between hypothalamic-pituitary adrenal-axis (HPA-axis), toll-like receptors (TLRs), as...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Arvin Haj-Mirzaian, Kiana Ramezanzadeh, Siavash Shariatzadeh, Michael Tajik, Farima Khalafi, Armin Tafazolimoghadam, Mahla Radmard, Alireza Rahbar, Fardad Pirri, Kiarash Kazemi, Ayda Khosravi, Niloufar Shababi, Ahmad Reza Dehpour
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4339b9a092014b5199adbab87449376a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4339b9a092014b5199adbab87449376a
record_format	dspace
spelling	oai:doaj.org-article:4339b9a092014b5199adbab87449376a2021-12-02T19:16:59ZRole of hypothalamic-pituitary adrenal-axis, toll-like receptors, and macrophage polarization in pre-atherosclerotic changes induced by social isolation stress in mice10.1038/s41598-021-98276-22045-2322https://doaj.org/article/4339b9a092014b5199adbab87449376a2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98276-2https://doaj.org/toc/2045-2322Abstract It has been well documented that chronic stress can induce atherosclerotic changes, however, the underlying mechanisms is yet to be established. In this regard, this study aimed to elucidate the relation between hypothalamic-pituitary adrenal-axis (HPA-axis), toll-like receptors (TLRs), as well as M1/M2 macrophage ratio and pre-atherosclerotic changes in social isolation stress (SIS) in mice. We used small interfering RNA against the glucocorticoid receptor (GR) to evaluate the relation between HPA-axis and TLRs. C57BL/6J mice were subjected to SIS and RT-PCR, ELISA, flow cytometry, and immunohistochemistry were used to assess the relations between pre-atherosclerotic changes and TLRs, macrophage polarization, pro-inflammatory cytokines, and cell adhesion molecules in aortic tissue. We used TAK-242 (0.3 mg/kg, intraperitoneally), a selective antagonist of TLR4, as a possible prophylactic treatment for atherosclerotic changes induced by SIS. We observed that isolated animals had higher serum concentration of corticosterone and higher body weight in comparison to normal animals. In isolated animals, results of in vitro study showed that knocking-down of the GR in bone marrow–derived monocytes significantly decreased the expression of TLR4. In vivo study suggested higher expression of TLR4 on circulating monocytes and higher M1/M2 ratio in aortic samples. Pathological study showed a mild pre-atherosclerotic change in isolated animals. Finally, we observed that treating animals with TAK-242 could significantly inhibit the pre-atherosclerotic changes. SIS can possibly increase the risk of atherosclerosis through inducing abnormal HPA-axis activity and subsequently lead to TLR4 up-regulation, vascular inflammation, high M1/M2 ratio in intima. Thus, TLR4 inhibitors might be a novel treatment to decrease the risk of atherosclerosis induced by chronic stress.Arvin Haj-MirzaianKiana RamezanzadehSiavash ShariatzadehMichael TajikFarima KhalafiArmin TafazolimoghadamMahla RadmardAlireza RahbarFardad PirriKiarash KazemiAyda KhosraviNiloufar ShababiAhmad Reza DehpourNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arvin Haj-Mirzaian Kiana Ramezanzadeh Siavash Shariatzadeh Michael Tajik Farima Khalafi Armin Tafazolimoghadam Mahla Radmard Alireza Rahbar Fardad Pirri Kiarash Kazemi Ayda Khosravi Niloufar Shababi Ahmad Reza Dehpour Role of hypothalamic-pituitary adrenal-axis, toll-like receptors, and macrophage polarization in pre-atherosclerotic changes induced by social isolation stress in mice
description	Abstract It has been well documented that chronic stress can induce atherosclerotic changes, however, the underlying mechanisms is yet to be established. In this regard, this study aimed to elucidate the relation between hypothalamic-pituitary adrenal-axis (HPA-axis), toll-like receptors (TLRs), as well as M1/M2 macrophage ratio and pre-atherosclerotic changes in social isolation stress (SIS) in mice. We used small interfering RNA against the glucocorticoid receptor (GR) to evaluate the relation between HPA-axis and TLRs. C57BL/6J mice were subjected to SIS and RT-PCR, ELISA, flow cytometry, and immunohistochemistry were used to assess the relations between pre-atherosclerotic changes and TLRs, macrophage polarization, pro-inflammatory cytokines, and cell adhesion molecules in aortic tissue. We used TAK-242 (0.3 mg/kg, intraperitoneally), a selective antagonist of TLR4, as a possible prophylactic treatment for atherosclerotic changes induced by SIS. We observed that isolated animals had higher serum concentration of corticosterone and higher body weight in comparison to normal animals. In isolated animals, results of in vitro study showed that knocking-down of the GR in bone marrow–derived monocytes significantly decreased the expression of TLR4. In vivo study suggested higher expression of TLR4 on circulating monocytes and higher M1/M2 ratio in aortic samples. Pathological study showed a mild pre-atherosclerotic change in isolated animals. Finally, we observed that treating animals with TAK-242 could significantly inhibit the pre-atherosclerotic changes. SIS can possibly increase the risk of atherosclerosis through inducing abnormal HPA-axis activity and subsequently lead to TLR4 up-regulation, vascular inflammation, high M1/M2 ratio in intima. Thus, TLR4 inhibitors might be a novel treatment to decrease the risk of atherosclerosis induced by chronic stress.
format	article
author	Arvin Haj-Mirzaian Kiana Ramezanzadeh Siavash Shariatzadeh Michael Tajik Farima Khalafi Armin Tafazolimoghadam Mahla Radmard Alireza Rahbar Fardad Pirri Kiarash Kazemi Ayda Khosravi Niloufar Shababi Ahmad Reza Dehpour
author_facet	Arvin Haj-Mirzaian Kiana Ramezanzadeh Siavash Shariatzadeh Michael Tajik Farima Khalafi Armin Tafazolimoghadam Mahla Radmard Alireza Rahbar Fardad Pirri Kiarash Kazemi Ayda Khosravi Niloufar Shababi Ahmad Reza Dehpour
author_sort	Arvin Haj-Mirzaian
title	Role of hypothalamic-pituitary adrenal-axis, toll-like receptors, and macrophage polarization in pre-atherosclerotic changes induced by social isolation stress in mice
title_short	Role of hypothalamic-pituitary adrenal-axis, toll-like receptors, and macrophage polarization in pre-atherosclerotic changes induced by social isolation stress in mice
title_full	Role of hypothalamic-pituitary adrenal-axis, toll-like receptors, and macrophage polarization in pre-atherosclerotic changes induced by social isolation stress in mice
title_fullStr	Role of hypothalamic-pituitary adrenal-axis, toll-like receptors, and macrophage polarization in pre-atherosclerotic changes induced by social isolation stress in mice
title_full_unstemmed	Role of hypothalamic-pituitary adrenal-axis, toll-like receptors, and macrophage polarization in pre-atherosclerotic changes induced by social isolation stress in mice
title_sort	role of hypothalamic-pituitary adrenal-axis, toll-like receptors, and macrophage polarization in pre-atherosclerotic changes induced by social isolation stress in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4339b9a092014b5199adbab87449376a
work_keys_str_mv	AT arvinhajmirzaian roleofhypothalamicpituitaryadrenalaxistolllikereceptorsandmacrophagepolarizationinpreatheroscleroticchangesinducedbysocialisolationstressinmice AT kianaramezanzadeh roleofhypothalamicpituitaryadrenalaxistolllikereceptorsandmacrophagepolarizationinpreatheroscleroticchangesinducedbysocialisolationstressinmice AT siavashshariatzadeh roleofhypothalamicpituitaryadrenalaxistolllikereceptorsandmacrophagepolarizationinpreatheroscleroticchangesinducedbysocialisolationstressinmice AT michaeltajik roleofhypothalamicpituitaryadrenalaxistolllikereceptorsandmacrophagepolarizationinpreatheroscleroticchangesinducedbysocialisolationstressinmice AT farimakhalafi roleofhypothalamicpituitaryadrenalaxistolllikereceptorsandmacrophagepolarizationinpreatheroscleroticchangesinducedbysocialisolationstressinmice AT armintafazolimoghadam roleofhypothalamicpituitaryadrenalaxistolllikereceptorsandmacrophagepolarizationinpreatheroscleroticchangesinducedbysocialisolationstressinmice AT mahlaradmard roleofhypothalamicpituitaryadrenalaxistolllikereceptorsandmacrophagepolarizationinpreatheroscleroticchangesinducedbysocialisolationstressinmice AT alirezarahbar roleofhypothalamicpituitaryadrenalaxistolllikereceptorsandmacrophagepolarizationinpreatheroscleroticchangesinducedbysocialisolationstressinmice AT fardadpirri roleofhypothalamicpituitaryadrenalaxistolllikereceptorsandmacrophagepolarizationinpreatheroscleroticchangesinducedbysocialisolationstressinmice AT kiarashkazemi roleofhypothalamicpituitaryadrenalaxistolllikereceptorsandmacrophagepolarizationinpreatheroscleroticchangesinducedbysocialisolationstressinmice AT aydakhosravi roleofhypothalamicpituitaryadrenalaxistolllikereceptorsandmacrophagepolarizationinpreatheroscleroticchangesinducedbysocialisolationstressinmice AT niloufarshababi roleofhypothalamicpituitaryadrenalaxistolllikereceptorsandmacrophagepolarizationinpreatheroscleroticchangesinducedbysocialisolationstressinmice AT ahmadrezadehpour roleofhypothalamicpituitaryadrenalaxistolllikereceptorsandmacrophagepolarizationinpreatheroscleroticchangesinducedbysocialisolationstressinmice
_version_	1718376908084740096

Role of hypothalamic-pituitary adrenal-axis, toll-like receptors, and macrophage polarization in pre-atherosclerotic changes induced by social isolation stress in mice

Ejemplares similares