ArticleCell communication and signaling : CCS2024
CD73/adenosine axis exerts cardioprotection against hypobaric hypoxia-induced metabolic shift and myocarditis in a sex-dependent manner.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 4 citations in OpenAlex.
- Circulating CD38 shows stronger association with incident heart failure in women despite lower levels: sex differences and kidney-function context.Biology of sex differences · 2026Article
- Review
- CD73 activity controls cytotoxic CD4 T-cell response driving myocardial pathology in chronic Chagas disease.Frontiers in immunology · 2026Article
- Erythrocytes enhance oxygen-carrying capacity through self-regulation.Frontiers in physiology · 2025Review
- Levocarnitine improves cardiac energy metabolic remodeling in myocarditis mice.Frontiers in pharmacology · 2025Article
- 4-Pyridone-3-carboxamide-1-β-D-ribonucleoside Reduces Cyclophosphamide Effects and Induces Endothelial Inflammation in Murine Breast Cancer Model.International journal of molecular sciences · 2024Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundClinical and experimental studies have shown that the myocardial inflammatory response during pathological events varies between males and females. However, the cellular and molecular mechanisms of these sex differences remain elusive. CD73/adenosine axis has been linked to anti-inflammatory responses, but its sex-specific cardioprotective role is unclear. The present study aimed to investigate whether the CD73/adenosine axis elicits sex-dependent cardioprotection during metabolic changes and myocarditis induced by hypobaric hypoxia.
methodsFor 7 days, male and female mice received daily injections of the CD73 inhibitor adenosine 5'- (α, β-methylene) diphosphate (APCP) 10 mg/kg/day while they were kept under normobaric normoxic and hypobaric hypoxic conditions. We evaluated the effects of hypobaric hypoxia on the CD73/adenosine axis, myocardial hypertrophy, and cardiac electrical activity and function. In addition, metabolic homeostasis and immunoregulation were investigated to clarify the sex-dependent cardioprotection of the CD73/adenosine axis.
resultsHypobaric hypoxia-induced cardiac dysfunction and adverse remodeling were more pronounced in male mice. Also, male mice had hyperactivity of the CD73/adenosine axis, which aggravated myocarditis and metabolic shift compared to female mice. In addition, CD73 inhibition triggered prostatic acid phosphatase ectonucleotidase enzymatic activity to sustain adenosine overproduction in male mice but not in female mice. Moreover, dual inhibition prostatic acid phosphatase and CD73 enzymatic activities in male mice moderated adenosine content, alleviating glycolytic shift and proinflammatory response.
conclusionThe CD73/adenosine axis confers a sex-dependent cardioprotection. In addition, extracellular adenosine production in the hearts of male mice is influenced by prostatic acid phosphatase and tissue nonspecific alkaline phosphatase.
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