One of the more subtle forms of damage caused by the high blood pressure of hypertension is the promotion of fibrosis in the blood vessel wall, causing thickening of that structure. This is implicated in the progression of cardiovascular disease for blood vessels in the heart, particularly the microvasculature, but it causes problems elsewhere in the body as well. Here researchers demonstrate that interfering in IL-9 signaling can reverse this fibrosis to some degree. Given the behaviors of senescent cells, implicated in fibrosis, it would be interesting to see the degree to which this IL-9 signaling is a consequence of cellular senescence.
Elevated blood pressure can cause a condition known as perivascular fibrosis, where the outside wall of a blood vessel thickens due to connective tissue build-up. Although recent data has suggested that the thickening is due to the activation of T-cells, the defenders of our immune system, the underlying mechanisms are not well known. To further investigate how fibrosis develops, researchers profiled the peripheral blood mononuclear immune cells from 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 IL-9 neutralizing antibodies, they observed a reversal of the fibrosis and prevention of organ dysfunction, building a stronger case for targeting this pathway. "Given that hypertension contributes to a considerable number of cardiovascular-related deaths globally, we wanted to look into the depths of perivascular fibrosis for potential drug targets. We are eager to continue investigating KLF10-IL-9 signaling to hopefully create effective treatments for vascular diseases."