GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation.
Johanna HelmstädterKarin KeppelerFranziska AustLeonie KüsterKatie FrenisKonstantina FilippouKsenija Vujacic-MirskiSimeon TsohataridisSanela KalinovicSwenja Kröller-SchönMatthias OelzeMarkus BosmannThomas MunzelAndreas DaiberSebastian StevenPublished in: Antioxidants (Basel, Switzerland) (2021)
Sepsis causes high mortality in the setting of septic shock. LEADER and other trials revealed cardioprotective and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) analogs like liraglutide (Lira). We previously demonstrated improved survival in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of GLP-1 degradation. Here we investigate the effects of Lira in the polymicrobial sepsis model of cecal ligation and puncture (CLP). C57BL/6J mice were intraperitoneally injected with Lira (200 µg/kg/d; 3 days) and sepsis induced by CLP after one day of GLP-1 analog treatment. Survival and body temperature were monitored. Aortic vascular function (isometric tension recording), protein expression (immunohistochemistry and dot blot) and gene expression (qRT-PCR) were determined. Endothelium-dependent relaxation in the aorta was impaired by CLP and correlated with markers of inflammation (e.g., interleukin 6 and inducible nitric oxide synthase) and oxidative stress (e.g., 3-nitrotyrosine) was higher in septic mice, all of which was almost completely normalized by Lira therapy. We demonstrate that the GLP-1 analog Lira ameliorates sepsis-induced endothelial dysfunction by the reduction of vascular inflammation and oxidative stress. Accordingly, the findings suggest that the antioxidant and anti-inflammatory effects of GLP-1 analogs may be a valuable tool to protect the cardiovascular system from dysbalanced inflammation in polymicrobial sepsis.
Keyphrases
- oxidative stress
- septic shock
- diabetic rats
- lps induced
- acute kidney injury
- anti inflammatory
- intensive care unit
- gene expression
- dna damage
- ischemia reperfusion injury
- nitric oxide synthase
- nitric oxide
- inflammatory response
- dna methylation
- aortic valve
- skeletal muscle
- type diabetes
- molecular docking
- immune response
- stem cells
- heart failure
- pulmonary hypertension
- insulin resistance
- cardiovascular events
- high glucose
- endoplasmic reticulum stress
- high intensity