1. Academic Validation
  2. Losartan attenuates sepsis-induced cardiomyopathy by regulating macrophage polarization via TLR4-mediated NF-κB and MAPK signaling

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

  • Pharmacol Res. 2022 Sep 28;185:106473. doi: 10.1016/j.phrs.2022.106473.
Xin-Sen Chen 1 Shu-Hang Wang 1 Chen-Yan Liu 1 Yu-Lei Gao 1 Xiang-Long Meng 1 Wei Wei 1 Song-Tao Shou 1 Yan-Cun Liu 2 Yan-Fen Chai 3
Affiliations

Affiliations

  • 1 Department of Emergency Medicine, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, China.
  • 2 Department of Emergency Medicine, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, China. Electronic address: yancunliu@tmu.edu.cn.
  • 3 Department of Emergency Medicine, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, China. Electronic address: chaiyanfen2012@126.com.
Abstract

Sepsis-induced cardiomyopathy (SIC) is a serious complication of sepsis with high mortality but no effective treatment. The Renin angiotensin (Ang) aldosterone 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-κB) 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.

Keywords

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

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