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p38MAPK 在动脉粥样硬化和主动脉瓣硬化中的作用。

Role of p38 MAPK in Atherosclerosis and Aortic Valve Sclerosis.

机构信息

Dr. Margarete-Fischer-Bosch-Institute of Clinical Pharmacology, 70376 Stuttgart, Germany.

University of Tuebingen, 72074 Tuebingen, Germany.

出版信息

Int J Mol Sci. 2018 Nov 27;19(12):3761. doi: 10.3390/ijms19123761.

Abstract

Atherosclerosis and aortic valve sclerosis are cardiovascular diseases with an increasing prevalence in western societies. Statins are widely applied in atherosclerosis therapy, whereas no pharmacological interventions are available for the treatment of aortic valve sclerosis. Therefore, valve replacement surgery to prevent acute heart failure is the only option for patients with severe aortic stenosis. Both atherosclerosis and aortic valve sclerosis are not simply the consequence of degenerative processes, but rather diseases driven by inflammatory processes in response to lipid-deposition in the blood vessel wall and the aortic valve, respectively. The p38 mitogen-activated protein kinase (MAPK) is involved in inflammatory signaling and activated in response to various intracellular and extracellular stimuli, including oxidative stress, cytokines, and growth factors, all of which are abundantly present in atherosclerotic and aortic valve sclerotic lesions. The responses generated by p38 MAPK signaling in different cell types present in the lesions are diverse and might support the progression of the diseases. This review summarizes experimental findings relating to p38 MAPK in atherosclerosis and aortic valve sclerosis and discusses potential functions of p38 MAPK in the diseases with the aim of clarifying its eligibility as a pharmacological target.

摘要

动脉粥样硬化和主动脉瓣硬化是心血管疾病,在西方社会的发病率不断上升。他汀类药物广泛应用于动脉粥样硬化的治疗,而对于主动脉瓣硬化尚无药物干预措施。因此,对于严重主动脉瓣狭窄的患者,瓣膜置换手术是预防急性心力衰竭的唯一选择。动脉粥样硬化和主动脉瓣硬化都不仅仅是退行性过程的结果,而是分别由血管壁和主动脉瓣中脂质沉积引起的炎症反应驱动的疾病。p38 丝裂原活化蛋白激酶(MAPK)参与炎症信号转导,并且在响应各种细胞内和细胞外刺激时被激活,包括氧化应激、细胞因子和生长因子,所有这些在动脉粥样硬化和主动脉瓣硬化病变中都大量存在。病变中不同细胞类型产生的 p38 MAPK 信号的反应是多样化的,可能会支持疾病的进展。本综述总结了与动脉粥样硬化和主动脉瓣硬化中 p38 MAPK 相关的实验结果,并讨论了 p38 MAPK 在这些疾病中的潜在功能,旨在阐明其作为药物靶点的资格。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c805/6321637/39fa2dc07151/ijms-19-03761-g001.jpg

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