- 著者
- Xiang Yin Linli Zhou Fei Han Jie Han Yuanyuan Zhang Zewei Sun Wenting Zhao Zhen Wang Liangrong Zheng
- 出版者
- 一般社団法人 日本動脈硬化学会
- 雑誌
- Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
- 巻号頁・発行日
- vol.24, no.1, pp.55-67, 2017-01-01 (Released:2017-01-01)
- 参考文献数
- 30
- 被引用文献数
- 9
Aim: Atherosclerosis is a chronic inflammatory disease, which leads to thrombosis and acute coronary syndrome. Matrix metalloproteinase-9 (MMP-9) is involved in the stability of the extracellular matrix (ECM) and atherosclerosis plaque. Until now, it is established that lipopolysaccharide (LPS) and norepinephrine (NE) are associated with the pathological process of atherosclerosis. However, the combined effect of LPS and NE on MMP-9 is unclear. We investigated the combined effect of LPS and NE on MMP-9 expression in human monocytes and the mechanism involved in the process.Methods: THP-1 cells were cultured and treated with LPS and/or NE. MMP-9 and TIMP-1 gene and protein expression were detected by real time PCR and ELISA, respectively. MMP-9 activity was detected by gelatin zymography. Adrenoceptor antagonists and MAPKs inhibitors were used to clarify the mechanism. Pathway-related proteins were detected by Western blot.Results: We found that NE enhances LPS-induced MMP-9 and TIMP-1 expression as well as MMP-9 activity in THP-1 cells. This effect is reversed by the beta (β)-adrenoceptor antagonist propranolol, extracellular signal-regulated kinases (ERK) inhibitor U0126, and c-Jun N-terminal kinase (JNK) inhibitor SP600125. NE enhances LPS-induced ERK/JNK phosphorylation. NE up-regulates LPS-induced c-Fos expression, which is counteracted by propranolol, U0126, and SP600125. Furthermore, c-Fos silence reverses the effect of NE on MMP-9 activity.Conclusions: Our results suggest that NE enhances LPS-induced MMP-9 expression through β-adrenergic receptor and downstream ERK/JNK-c-Fos pathway. This study may help us to understand the combined effect and mechanism of NE/LPS on MMP-9 expression.
- 著者
- Panpan He Huan Li Zhuxian Zhang Yuanyuan Zhang Tengfei Lin Yun Song Lishun Liu Min Liang Jing Nie Binyan Wang Yong Huo Fan Fan Hou Xiping Xu Xianhui Qin
- 出版者
- Japan Epidemiological Association
- 雑誌
- Journal of Epidemiology (ISSN:09175040)
- 巻号頁・発行日
- vol.33, no.3, pp.142-149, 2023-03-05 (Released:2023-03-05)
- 参考文献数
- 35
Background: The association between changes in estimated glomerular filtration rate (eGFR) over time and the risk of stroke remains inconclusive. We aimed to evaluate the relation of eGFR change during the China Stroke Primary Prevention Trial (CSPPT) with the risk of first stroke during the subsequent post-trial follow-up.Methods: A total of 11,742 hypertensive participants with two eGFR measurements (median measure interval, 4.4; interquartile range, 4.2–4.6 years) and without a history of stroke from the CSPPT were included in this analysis.Results: Over a median post-trial follow-up of 4.4 years, 729 first strokes were identified, of which 635 were ischemic, 88 were hemorrhagic, and 6 were uncertain types of strokes. Compared with those with 1 to <2% per year increase in eGFR (with the lowest stroke risk), those with an increase in eGFR of ≥4% per year had significantly increased risks of first stroke (adjusted hazard ratio [HR] 1.96; 95% confidence interval [CI], 1.10–3.50) and first ischemic stroke (adjusted HR 2.14; 95% CI, 1.17–3.90). Similarly, those with a decline in eGFR of ≥5% per year also had significantly increased first stroke (adjusted HR 2.13; 95% CI, 1.37–3.31) and first ischemic stroke (adjusted HR 1.89; 95% CI, 1.19–3.02) risk. However, there was no significant association between eGFR change and first hemorrhagic stroke. A similar result was found when the change in eGFR was quantified as an absolute annual change.Conclusion: In Chinese hypertensive patients, both the decline and increase of eGFR levels were independently associated with the risks of first stroke or first ischemic stroke.