The NO signalling pathway in aortic aneurysm and dissection.

Recent studies have shown that NO is a central mediator in diseases associated with thoracic aortic aneurysm, such as Marfan syndrome. The progressive dilation of the aorta in thoracic aortic aneurysm ultimately leads to aortic dissection. Unfortunately, current medical treatments have neither halt aortic enlargement nor prevented rupture, leaving surgical repair as the only effective treatment.

Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO.

Thoracic aortic aneurysm, as occurs in Marfan syndrome, is generally asymptomatic until dissection or rupture, requiring surgical intervention as the only available treatment. Here, we show that nitric oxide (NO) signaling dysregulates actin cytoskeleton dynamics in Marfan Syndrome smooth muscle cells and that NO-donors induce Marfan-like aortopathy in wild-type mice, indicating that a marked increase in NO suffices to induce aortopathy. Levels of nitrated proteins are higher in plasma from Marfan patients and mice and in aortic tissue from Marfan mice than in control samples, indicating elevated circulating and tissue NO.