4.7 Article

Losartan attenuates sepsis-induced cardiomyopathy by regulating macrophage polarization via TLR4-mediated NF-κB and MAPK signaling

期刊

PHARMACOLOGICAL RESEARCH
卷 185, 期 -, 页码 -

出版社

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2022.106473

关键词

Sepsis-induced cardiomyopathy; Angiotensin II type 1 receptor; Losartan; Macrophage polarization; Apoptosis

资金

  1. National Natural Science Foundation of China
  2. [81601714]
  3. [81871593]
  4. [82172120]

向作者/读者索取更多资源

This study investigated the association between the Ang II/AT1R axis and sepsis-induced cardiomyopathy (SIC) and found that the AT1R blocker losartan can reduce myocardial injury in SIC.
Sepsis-induced cardiomyopathy (SIC) is a serious complication of sepsis with high mortality but no effective treatment. The renin angiotensin (Ang) aldostemne system (RAAS) is activated in patients with sepsis but it is unclear how the Ang II/Ang II type 1 receptor (AT1R) axis contributes to SIC. This study examined the link between the Ang II/AT1R axis and SIC as well as the protective effect of AT1R blockers (ARBs). The Ang II level in peripheral plasma and AT1R expression on monocytes were significantly higher in patients with SIC compared with those in non-SIC patients and healthy controls and were correlated with the degree of myocardial injury. The ARB losartan reduced the infiltration of neutrophils, monocytes, and macrophages into the heart and spleen of SIC mice. Additionally, losartan regulated macrophage polarization from the M1 to the M2 subtype via nuclear factor-kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby maintaining the mitochondrial dynamics balance in cardiomyocytes and reducing oxidative stress and cardiomyocyte apoptosis. In conclusion, the plasma Ang II level and AT1R expression on plasma monocytes are an important biomarker in SIC. Therapeutic targeting of AT1R, for example with losartan, can potentially protect against myocardial injury in SIC.

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