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Heparanase upregulation from adipocyte associates with inflammation and endothelial injury in diabetic condition

BACKGROUND: Diabetes Mellitus (DM) is one of the metabolic diseases which leads to fatty tissue injury, and consequently inducing lipotoxicity and cellular senescence. This condition contributes to endothelial dysfunction with chronic inflammation and organ damage. Heparanase which has a role in dis...

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Autores principales: Arfian, Nur, Setyaningsih, Wiwit Ananda Wahyu, Romi, Muhammad Mansyur, Sari, Dwi Cahyani Ratna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912933/
https://www.ncbi.nlm.nih.gov/pubmed/31890010
http://dx.doi.org/10.1186/s12919-019-0181-x
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author Arfian, Nur
Setyaningsih, Wiwit Ananda Wahyu
Romi, Muhammad Mansyur
Sari, Dwi Cahyani Ratna
author_facet Arfian, Nur
Setyaningsih, Wiwit Ananda Wahyu
Romi, Muhammad Mansyur
Sari, Dwi Cahyani Ratna
author_sort Arfian, Nur
collection PubMed
description BACKGROUND: Diabetes Mellitus (DM) is one of the metabolic diseases which leads to fatty tissue injury, and consequently inducing lipotoxicity and cellular senescence. This condition contributes to endothelial dysfunction with chronic inflammation and organ damage. Heparanase which has a role in disrupting endothelial surface layer (glycocalyx) may promote endothelial Nitric oxide synthase (eNOS) reduction and inflammation. However, its relationship with DM and organ injury has not been fully elucidated yet. This study aimed to determine how heparanase from fatty tissue may contribute to endothelial dysfunction and inflammation in patients with hyperglycemia and in a hyperglycemia model in rats. METHODS: This population study with a cross-sectional design was conducted with 28 subjects without diagnosis and medication of DM. Fasting blood glucose levels, lipid profile, heparanase protein, MCP-1 protein and HbA1c were quantified. In vivo study was performed with a diabetic model in Wistar rats induced with streptozotocin 60 mg/kg body weight by single intraperitoneal injection. Rats were euthanized after 1 month (DM1 group, n = 6), 2 months (DM2 group, n = 6) and 4 months (DM4 group, n = 6). White Adipose Tissue (WAT) was harvested from visceral fat. Real Time and Reverse Transcriptase-PCR (RT-PCR) was done to quantify expressions of heparanase, MCP-1, eNOS, IL-6 and p-16 (senescence). Immunostaining was performed to localize MCP-1 and macrophage (CD68). Western blot tests were used to examine eNOS, MCP-1 and heparanase protein expression. RESULTS: This study revealed associations between blood glucose levels with higher HbA1c, LDL, cholesterol, heparanase and MCP-1. The in vivo study also revealed lipid levels as the source of Heparanase and MCP-1 mRNA and protein expressions. This finding was associated with inflammation, cellular senescence and macrophage infiltration in fat tissue based on immunostaining and qRT-PCR analysis. RT-PCR revealed significantly lower expression of eNOS and higher expression of IL-6 in DM groups compared to the control group. CONCLUSION: Heparanase upregulation in fat tissue was associated with endothelial injury and inflammation in hyperglycemia conditions.
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spelling pubmed-69129332019-12-30 Heparanase upregulation from adipocyte associates with inflammation and endothelial injury in diabetic condition Arfian, Nur Setyaningsih, Wiwit Ananda Wahyu Romi, Muhammad Mansyur Sari, Dwi Cahyani Ratna BMC Proc Research BACKGROUND: Diabetes Mellitus (DM) is one of the metabolic diseases which leads to fatty tissue injury, and consequently inducing lipotoxicity and cellular senescence. This condition contributes to endothelial dysfunction with chronic inflammation and organ damage. Heparanase which has a role in disrupting endothelial surface layer (glycocalyx) may promote endothelial Nitric oxide synthase (eNOS) reduction and inflammation. However, its relationship with DM and organ injury has not been fully elucidated yet. This study aimed to determine how heparanase from fatty tissue may contribute to endothelial dysfunction and inflammation in patients with hyperglycemia and in a hyperglycemia model in rats. METHODS: This population study with a cross-sectional design was conducted with 28 subjects without diagnosis and medication of DM. Fasting blood glucose levels, lipid profile, heparanase protein, MCP-1 protein and HbA1c were quantified. In vivo study was performed with a diabetic model in Wistar rats induced with streptozotocin 60 mg/kg body weight by single intraperitoneal injection. Rats were euthanized after 1 month (DM1 group, n = 6), 2 months (DM2 group, n = 6) and 4 months (DM4 group, n = 6). White Adipose Tissue (WAT) was harvested from visceral fat. Real Time and Reverse Transcriptase-PCR (RT-PCR) was done to quantify expressions of heparanase, MCP-1, eNOS, IL-6 and p-16 (senescence). Immunostaining was performed to localize MCP-1 and macrophage (CD68). Western blot tests were used to examine eNOS, MCP-1 and heparanase protein expression. RESULTS: This study revealed associations between blood glucose levels with higher HbA1c, LDL, cholesterol, heparanase and MCP-1. The in vivo study also revealed lipid levels as the source of Heparanase and MCP-1 mRNA and protein expressions. This finding was associated with inflammation, cellular senescence and macrophage infiltration in fat tissue based on immunostaining and qRT-PCR analysis. RT-PCR revealed significantly lower expression of eNOS and higher expression of IL-6 in DM groups compared to the control group. CONCLUSION: Heparanase upregulation in fat tissue was associated with endothelial injury and inflammation in hyperglycemia conditions. BioMed Central 2019-12-16 /pmc/articles/PMC6912933/ /pubmed/31890010 http://dx.doi.org/10.1186/s12919-019-0181-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Arfian, Nur
Setyaningsih, Wiwit Ananda Wahyu
Romi, Muhammad Mansyur
Sari, Dwi Cahyani Ratna
Heparanase upregulation from adipocyte associates with inflammation and endothelial injury in diabetic condition
title Heparanase upregulation from adipocyte associates with inflammation and endothelial injury in diabetic condition
title_full Heparanase upregulation from adipocyte associates with inflammation and endothelial injury in diabetic condition
title_fullStr Heparanase upregulation from adipocyte associates with inflammation and endothelial injury in diabetic condition
title_full_unstemmed Heparanase upregulation from adipocyte associates with inflammation and endothelial injury in diabetic condition
title_short Heparanase upregulation from adipocyte associates with inflammation and endothelial injury in diabetic condition
title_sort heparanase upregulation from adipocyte associates with inflammation and endothelial injury in diabetic condition
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912933/
https://www.ncbi.nlm.nih.gov/pubmed/31890010
http://dx.doi.org/10.1186/s12919-019-0181-x
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