Diminished vasculogenesis under inflammatory conditions is mediated by Activin A

Area of Science:

• Vascular Biology
• Inflammation Research
• Cell Signaling

Background:

• Severe inflammatory stress can cause vessel rarefaction and fibrosis, impairing tissue recovery.
• The precise signaling pathways driving these vascular changes are not fully understood.
• Elevated Activin A levels in patients with ischemic and inflammatory diseases suggest a role in pathology.

Purpose of the Study:

• To investigate the role of Activin A in vasculogenesis under inflammatory conditions.
• To elucidate the signaling pathways by which inflammatory cells impact vascular homeostasis.
• To determine if targeting Activin A can mitigate inflammatory damage to vasculature.

Main Methods:

• Co-culture of endothelial cells (EC) and adipose stromal cells (ASC) exposed to activated peripheral blood mononuclear cells (aPBMC).
• Measurement of Activin A secretion, Inhibin Ba mRNA expression, and EC tubulogenesis.
• Identification of key inflammatory cytokines (TNFα, IL-1β) inducing Activin A.
• In vitro and in vivo experiments using Activin A neutralizing antibodies.

Main Results:

• Inflammatory stimuli (aPBMC) reduced EC tubulogenesis and caused vessel rarefaction, correlating with increased Activin A secretion.
• TNFα and IL-1β in aPBMC secretome were identified as key inducers of Activin A in EC and perivascular cells.
• Blocking Activin A ameliorated the detrimental effects of inflammation on EC tubulogenesis and in vivo vessel formation.

Conclusions:

• Inflammatory cells detrimentally affect vessel formation and homeostasis via pathways involving Activin A.
• Activin A plays a central role in mediating inflammatory damage to vasculature.
• Interfering with Activin A during inflammatory or ischemic insults may preserve vasculature and enhance tissue recovery.