IL-18 Mediates Vascular Calcification Induced by High-Fat Diet in Rats With Chronic Renal Failure

Objective: Vascular calcification (VC) is an important predictor of cardiovascular morbidity and mortality in patients with chronic renal failure (CRF). It is well-known that obesity and metabolic syndrome (OB/MS) predicts poor prognosis of CRF patients. However, the influence of OB/MS on VC in CRF...

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Autores principales:	Yinyin Zhang, Kun Zhang, Yuling Zhang, Lingqu Zhou, Hui Huang, Jingfeng Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	IL-18 vascular calcification chronic renal failure high-fat diet MAPK Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/4acfde0734614c71a675c450699343ea
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spelling	oai:doaj.org-article:4acfde0734614c71a675c450699343ea2021-11-30T23:30:46ZIL-18 Mediates Vascular Calcification Induced by High-Fat Diet in Rats With Chronic Renal Failure2297-055X10.3389/fcvm.2021.724233https://doaj.org/article/4acfde0734614c71a675c450699343ea2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.724233/fullhttps://doaj.org/toc/2297-055XObjective: Vascular calcification (VC) is an important predictor of cardiovascular morbidity and mortality in patients with chronic renal failure (CRF). It is well-known that obesity and metabolic syndrome (OB/MS) predicts poor prognosis of CRF patients. However, the influence of OB/MS on VC in CRF patients isn't clear. IL-18 mediates OB/MS-related inflammation, but whether IL-18 is involved in OB/MS -mediated VC in CRF patients hasn't been studied. In this study, it was explored that whether OB/MS caused by high-fat diet (HFD) can affect the level of serum IL-18 and aggravate the degree of VC in CRF rats. Furthermore, it was studied that whether IL-18 induces rat vascular smooth muscle cells (VSMCs) calcification by activating the MAPK pathways.Approach: The rats were randomly assigned to the sham-operated, CRF and CRF + HFD groups. CRF was induced by 5/6 nephrectomy. Serum IL-18 levels and aortic calcification indicators were compared in each group. Primary rat VSMCs calcification were induced by β-glycerophosphate and exposed to IL-18. VSMCs were also treated with MAPK inhibitors.Results: The weight, serum levels of hsCRP, TG and LDL-C in CRF + HFD group were significantly higher than those in sham-operated and CRF groups (p < 0.05). Compared with the sham-operated group, the calcium content and the expression of BMP-2 of aorta in CRF and CRF + HFD groups were significantly increased (p < 0.05). Moreover, the calcium content and the expression of BMP-2 of aorta in CRF + HFD group was significantly higher than those in CRF group (p < 0.05). And the serum IL-18 level was positively correlated with aortic calcium content. It was also found that p38 inhibitor SB203580 can suppress the VSMCs calcification and osteoblast phenotype differentiation induced by IL-18. But the JNK inhibitor SP600125 can't suppress the VSMCs calcification and osteoblast phenotype differentiation induced by IL-18.Conclusions: These findings suggest that obesity-related inflammation induced by high-fat diet could exacerbate VC in CRF rats. Furthermore, serum IL-18 level had a positive correlation with the degree of VC. It is also found that IL-18 promoted osteogenic differentiation and calcification of rat VSMCs via p38 pathway activation.Yinyin ZhangKun ZhangYuling ZhangLingqu ZhouHui HuangJingfeng WangFrontiers Media S.A.articleIL-18vascular calcificationchronic renal failurehigh-fat dietMAPKDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	IL-18 vascular calcification chronic renal failure high-fat diet MAPK Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	IL-18 vascular calcification chronic renal failure high-fat diet MAPK Diseases of the circulatory (Cardiovascular) system RC666-701 Yinyin Zhang Kun Zhang Yuling Zhang Lingqu Zhou Hui Huang Jingfeng Wang IL-18 Mediates Vascular Calcification Induced by High-Fat Diet in Rats With Chronic Renal Failure
description	Objective: Vascular calcification (VC) is an important predictor of cardiovascular morbidity and mortality in patients with chronic renal failure (CRF). It is well-known that obesity and metabolic syndrome (OB/MS) predicts poor prognosis of CRF patients. However, the influence of OB/MS on VC in CRF patients isn't clear. IL-18 mediates OB/MS-related inflammation, but whether IL-18 is involved in OB/MS -mediated VC in CRF patients hasn't been studied. In this study, it was explored that whether OB/MS caused by high-fat diet (HFD) can affect the level of serum IL-18 and aggravate the degree of VC in CRF rats. Furthermore, it was studied that whether IL-18 induces rat vascular smooth muscle cells (VSMCs) calcification by activating the MAPK pathways.Approach: The rats were randomly assigned to the sham-operated, CRF and CRF + HFD groups. CRF was induced by 5/6 nephrectomy. Serum IL-18 levels and aortic calcification indicators were compared in each group. Primary rat VSMCs calcification were induced by β-glycerophosphate and exposed to IL-18. VSMCs were also treated with MAPK inhibitors.Results: The weight, serum levels of hsCRP, TG and LDL-C in CRF + HFD group were significantly higher than those in sham-operated and CRF groups (p < 0.05). Compared with the sham-operated group, the calcium content and the expression of BMP-2 of aorta in CRF and CRF + HFD groups were significantly increased (p < 0.05). Moreover, the calcium content and the expression of BMP-2 of aorta in CRF + HFD group was significantly higher than those in CRF group (p < 0.05). And the serum IL-18 level was positively correlated with aortic calcium content. It was also found that p38 inhibitor SB203580 can suppress the VSMCs calcification and osteoblast phenotype differentiation induced by IL-18. But the JNK inhibitor SP600125 can't suppress the VSMCs calcification and osteoblast phenotype differentiation induced by IL-18.Conclusions: These findings suggest that obesity-related inflammation induced by high-fat diet could exacerbate VC in CRF rats. Furthermore, serum IL-18 level had a positive correlation with the degree of VC. It is also found that IL-18 promoted osteogenic differentiation and calcification of rat VSMCs via p38 pathway activation.
format	article
author	Yinyin Zhang Kun Zhang Yuling Zhang Lingqu Zhou Hui Huang Jingfeng Wang
author_facet	Yinyin Zhang Kun Zhang Yuling Zhang Lingqu Zhou Hui Huang Jingfeng Wang
author_sort	Yinyin Zhang
title	IL-18 Mediates Vascular Calcification Induced by High-Fat Diet in Rats With Chronic Renal Failure
title_short	IL-18 Mediates Vascular Calcification Induced by High-Fat Diet in Rats With Chronic Renal Failure
title_full	IL-18 Mediates Vascular Calcification Induced by High-Fat Diet in Rats With Chronic Renal Failure
title_fullStr	IL-18 Mediates Vascular Calcification Induced by High-Fat Diet in Rats With Chronic Renal Failure
title_full_unstemmed	IL-18 Mediates Vascular Calcification Induced by High-Fat Diet in Rats With Chronic Renal Failure
title_sort	il-18 mediates vascular calcification induced by high-fat diet in rats with chronic renal failure
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4acfde0734614c71a675c450699343ea
work_keys_str_mv	AT yinyinzhang il18mediatesvascularcalcificationinducedbyhighfatdietinratswithchronicrenalfailure AT kunzhang il18mediatesvascularcalcificationinducedbyhighfatdietinratswithchronicrenalfailure AT yulingzhang il18mediatesvascularcalcificationinducedbyhighfatdietinratswithchronicrenalfailure AT lingquzhou il18mediatesvascularcalcificationinducedbyhighfatdietinratswithchronicrenalfailure AT huihuang il18mediatesvascularcalcificationinducedbyhighfatdietinratswithchronicrenalfailure AT jingfengwang il18mediatesvascularcalcificationinducedbyhighfatdietinratswithchronicrenalfailure
_version_	1718406200098291712

IL-18 Mediates Vascular Calcification Induced by High-Fat Diet in Rats With Chronic Renal Failure

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