High blood pressure can cause a condition known as perivascular fibrosis, in which the outer lining of a blood vessel thickens due to buildup of connective tissue.

Although recent data suggests that the thickening is due to the activation of T cells, defenders of our immune system, the underlying mechanisms are not well known. To further investigate the development of fibrosis, the Brigham researchers profiled mononuclear immune cells from the peripheral blood of patients with high blood pressure. In doing so, they discovered two relevant mediators of fibrosis and potential therapeutic targets: a transcription factor, KLF10, and a cytokine, IL-9.

When researchers injected mice with neutralizing antibodies to IL-9, they observed reversal of fibrosis and prevention of organ dysfunction, strengthening the case for targeting this pathway.

Since hypertension contributes to a considerable number of cardiovascular disease-related deaths worldwide, we wanted to look into the depths of perivascular fibrosis for potential drug targets. We look forward to continuing to study KLF10-IL-9 signaling to hopefully create effective treatments for vascular disease. »


Mark W. Feinberg, MD, senior author, Division of Cardiovascular Medicine

Source:

Brigham and Women’s Hospital

Journal reference:

Zhuang, R. et al. (2022) Perivascular fibrosis is mediated by a KLF10-IL-9 signaling axis in CD4+ T cells. Traffic research. doi.org/10.1161/CIRCRESAHA.121.320420.