Cargando…

Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis

Galectin-3 (Gal-3) is a 26-kDa lectin that regulates many aspects of inflammatory cell behavior. We assessed the hypothesis that increased levels of Gal-3 contribute to abdominal aortic aneurysm (AAA) progression by enhancing monocyte chemoattraction through macrophage activation. We analyzed the pl...

Descripción completa

Detalles Bibliográficos
Autores principales: Lu, Hsin-Ying, Shih, Chun-Ming, Huang, Chun-Yang, Wu, Alexander T. H., Cheng, Tsai-Mu, Mi, Fwu-Long, Shih, Chun-Che
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663490/
https://www.ncbi.nlm.nih.gov/pubmed/33158139
http://dx.doi.org/10.3390/ijms21218257
_version_ 1783609638768345088
author Lu, Hsin-Ying
Shih, Chun-Ming
Huang, Chun-Yang
Wu, Alexander T. H.
Cheng, Tsai-Mu
Mi, Fwu-Long
Shih, Chun-Che
author_facet Lu, Hsin-Ying
Shih, Chun-Ming
Huang, Chun-Yang
Wu, Alexander T. H.
Cheng, Tsai-Mu
Mi, Fwu-Long
Shih, Chun-Che
author_sort Lu, Hsin-Ying
collection PubMed
description Galectin-3 (Gal-3) is a 26-kDa lectin that regulates many aspects of inflammatory cell behavior. We assessed the hypothesis that increased levels of Gal-3 contribute to abdominal aortic aneurysm (AAA) progression by enhancing monocyte chemoattraction through macrophage activation. We analyzed the plasma levels of Gal-3 in 76 patients with AAA (AAA group) and 97 controls (CTL group) as well as in angiotensin II (Ang-II)-infused ApoE knockout mice. Additionally, conditioned media (CM) were used to polarize THP-1 monocyte to M1 macrophages with or without Gal-3 inhibition through small interfering RNA targeted deletion to investigate whether Gal-3 inhibition could attenuate macrophage-induced inflammation and smooth muscle cell (SMC) apoptosis. Our results showed a markedly increased expression of Gal-3 in the plasma and aorta in the AAA patients and experimental mice compared with the CTL group. An in vitro study demonstrated that the M1 cells exhibited increased Gal-3 expression. Gal-3 inhibition markedly decreased the quantity of macrophage-induced inflammatory regulators, including IL-8, TNF-α, and IL-1β, as well as messenger RNA expression and MMP-9 activity. Moreover, Gal-3-deficient CM weakened SMC apoptosis through Fas activation. These findings prove that Gal-3 may contribute to AAA progression by the activation of inflammatory macrophages, thereby promoting SMC apoptosis.
format Online
Article
Text
id pubmed-7663490
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-76634902020-11-14 Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis Lu, Hsin-Ying Shih, Chun-Ming Huang, Chun-Yang Wu, Alexander T. H. Cheng, Tsai-Mu Mi, Fwu-Long Shih, Chun-Che Int J Mol Sci Article Galectin-3 (Gal-3) is a 26-kDa lectin that regulates many aspects of inflammatory cell behavior. We assessed the hypothesis that increased levels of Gal-3 contribute to abdominal aortic aneurysm (AAA) progression by enhancing monocyte chemoattraction through macrophage activation. We analyzed the plasma levels of Gal-3 in 76 patients with AAA (AAA group) and 97 controls (CTL group) as well as in angiotensin II (Ang-II)-infused ApoE knockout mice. Additionally, conditioned media (CM) were used to polarize THP-1 monocyte to M1 macrophages with or without Gal-3 inhibition through small interfering RNA targeted deletion to investigate whether Gal-3 inhibition could attenuate macrophage-induced inflammation and smooth muscle cell (SMC) apoptosis. Our results showed a markedly increased expression of Gal-3 in the plasma and aorta in the AAA patients and experimental mice compared with the CTL group. An in vitro study demonstrated that the M1 cells exhibited increased Gal-3 expression. Gal-3 inhibition markedly decreased the quantity of macrophage-induced inflammatory regulators, including IL-8, TNF-α, and IL-1β, as well as messenger RNA expression and MMP-9 activity. Moreover, Gal-3-deficient CM weakened SMC apoptosis through Fas activation. These findings prove that Gal-3 may contribute to AAA progression by the activation of inflammatory macrophages, thereby promoting SMC apoptosis. MDPI 2020-11-04 /pmc/articles/PMC7663490/ /pubmed/33158139 http://dx.doi.org/10.3390/ijms21218257 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lu, Hsin-Ying
Shih, Chun-Ming
Huang, Chun-Yang
Wu, Alexander T. H.
Cheng, Tsai-Mu
Mi, Fwu-Long
Shih, Chun-Che
Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis
title Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis
title_full Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis
title_fullStr Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis
title_full_unstemmed Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis
title_short Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis
title_sort galectin-3 modulates macrophage activation and contributes smooth muscle cells apoptosis in abdominal aortic aneurysm pathogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663490/
https://www.ncbi.nlm.nih.gov/pubmed/33158139
http://dx.doi.org/10.3390/ijms21218257
work_keys_str_mv AT luhsinying galectin3modulatesmacrophageactivationandcontributessmoothmusclecellsapoptosisinabdominalaorticaneurysmpathogenesis
AT shihchunming galectin3modulatesmacrophageactivationandcontributessmoothmusclecellsapoptosisinabdominalaorticaneurysmpathogenesis
AT huangchunyang galectin3modulatesmacrophageactivationandcontributessmoothmusclecellsapoptosisinabdominalaorticaneurysmpathogenesis
AT wualexanderth galectin3modulatesmacrophageactivationandcontributessmoothmusclecellsapoptosisinabdominalaorticaneurysmpathogenesis
AT chengtsaimu galectin3modulatesmacrophageactivationandcontributessmoothmusclecellsapoptosisinabdominalaorticaneurysmpathogenesis
AT mifwulong galectin3modulatesmacrophageactivationandcontributessmoothmusclecellsapoptosisinabdominalaorticaneurysmpathogenesis
AT shihchunche galectin3modulatesmacrophageactivationandcontributessmoothmusclecellsapoptosisinabdominalaorticaneurysmpathogenesis