Rubella virus infection in endothelial cells reduces angiogenesis via interferon beta-induced CXCL10.

Rubella virus (RuV) infection during pregnancy can lead to abortion, stillbirth, and embryonic defects, resulting in congenital rubella syndrome (CRS). It is estimated that there are still 100,000 cases of CRS per year in developing regions with a mortality rate of over 30%. The molecular pathomechanisms remain largely unexplored. Placental endothelial cells (EC) are frequently infected with RuV. RuV reduced the angiogenic and migratory capacity of primary human EC, as confirmed by treatment of EC with serum from RuV IgM-positive patients. Next generation sequencing analysis revealed the induction of antiviral interferon (IFN) type I and III and CXCL10. The RuV-induced transcriptional profile resembled the effects of IFN-ß treatment. The RuV-mediated inhibition of angiogenesis was reversed by treatment with blocking and neutralizing antibodies targeting CXCL10 and the IFN-ß receptor. The data identify an important role for antiviral IFN-mediated induction of CXCL10 in the control of EC function during RuV infection.

Leptin treatment has vasculo-protective effects in lipodystrophic mice.

Lipodystrophy syndromes (LDs) are characterized by loss of adipose tissue, metabolic complications such as dyslipidemia, insulin resistance, and fatty liver disease, as well as accelerated atherosclerosis. As a result of adipose tissue deficiency, the systemic concentration of the adipokine leptin is reduced. A current promising therapeutic option for patients with LD is treatment with recombinant leptin (metreleptin), resulting in reduced risk of mortality. Here, we investigate the effects of leptin on endothelial to mesenchymal transition (EndMT), which impair the functional properties of endothelial cells and promotes atherogenesis in LD. Leptin treatment reduced inflammation and TGF-ß2-induced expression of mesenchymal genes and prevented impairment of endothelial barrier function. Treatment of lipodystrophic- and atherosclerosis-prone animals (Ldlr-/-; aP2-nSrebp1c-Tg) with leptin reduced macrophage accumulation in atherosclerotic lesions, vascular plaque protrusion, and the number of endothelial cells with mesenchymal gene expression, confirming a reduction in EndMT in LD after leptin treatment. Treatment with leptin inhibited LD-mediated induction of the proatherosclerotic cytokine growth/differentiation factor 15 (GDF15). Inhibition of GDF15 reduced EndMT induction triggered by plasma from patients with LD. Our study reveals that in addition to the effects on adipose tissue function, leptin treatment exerts beneficial effects protecting endothelial function and identity in LD by reducing GDF15.