Blockade of caspase cascade overcomes malaria-associated acute respiratory distress syndrome in mice.
Michelle K SercundesLuana Dos Santos OrtolanViviane da Silva JulioLeonardo M BellaThatyane de Castro QuirinoDaniela DeboneMarcela S Carneiro-RamosMarcelo A ChristoffoleteJoilson Oliveira MartinsMaria Regina D'Império LimaJosé M AlvarezGustavo P Amarante-MendesLígia Antunes GonçalvesClaudio R F MarinhoSabrina EpiphanioPublished in: Cell death & disease (2022)
Malaria is an enormous burden on global health that caused 409,000 deaths in 2019. Severe malaria can manifest in the lungs, an illness known as acute respiratory distress syndrome (ARDS). Not much is known about the development of malaria-associated ARDS (MA-ARDS), especially regarding cell death in the lungs. We had previously established a murine model that mimics various human ARDS aspects, such as pulmonary edema, hemorrhages, pleural effusion, and hypoxemia, using DBA/2 mice infected with Plasmodium berghei ANKA. Here, we explored the mechanisms and the involvement of apoptosis in this syndrome. We found that apoptosis contributes to the pathogenesis of MA-ARDS, primarily as facilitators of the alveolar-capillary barrier breakdown. The protection of pulmonary endothelium by inhibiting caspase activation could be a promising therapeutic strategy to prevent the pathogenicity of MA-ARDS. Therefore, intervention in the programmed death cell mechanism could help patients not to develop severe malaria.
Keyphrases
- acute respiratory distress syndrome
- plasmodium falciparum
- cell death
- extracorporeal membrane oxygenation
- mechanical ventilation
- cell cycle arrest
- global health
- oxidative stress
- end stage renal disease
- pulmonary hypertension
- randomized controlled trial
- endothelial cells
- chronic kidney disease
- early onset
- public health
- nitric oxide
- ejection fraction
- signaling pathway
- induced apoptosis
- newly diagnosed
- metabolic syndrome
- escherichia coli
- stem cells
- single cell
- peritoneal dialysis
- bone marrow
- high fat diet induced
- prognostic factors
- drug induced
- cystic fibrosis
- patient reported outcomes
- insulin resistance
- skeletal muscle
- cell proliferation
- intensive care unit
- type diabetes