Paracrine Mediator of Aortic Dissection
For more than 30 years, the endothelium has assumed increasingly greater importance in our understanding of the development of vascular pathology. This includes the discoveries that the endothelium releases the powerful vasodilator and antiplatelet mediators prostacyclin and nitric oxide, as well as its role in governing permeability, inflammation, and monocyte/macrophage infiltration of the blood vessel. In this issue of Circulation, Fan et al1 show that boosting endothelial-derived oxidants in the mouse aorta by overexpression of the nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase isoform 2 (Nox2) during prolonged angiotensin II–induced hypertension results in a high incidence of infrarenal aortic dissection.
Article see p 2661
Aortic dissections are often associated with aneurysms, which may affect both thoracic (TAA) and abdominal (AAA) regions, but can occur also in the absence of aneurysm. There are currently no approved drug treatments against these deadly aortopathies. Limited treatment options include blood pressure control as a means of decreasing the risk of rupture and endovascular or open surgical repair, a procedure with high risk of morbidity and mortality. Although the elucidation of the mechanisms responsible for early aortic pathological changes that precede overt dissection remains very challenging in humans, animal models suggest that medial degeneration, consisting of vascular smooth muscle cell apoptosis and elastin fragmentation, are early features. The work by Fan et al identifies release from the endothelium of the proinflammatory cytokine cyclophillin A (cypA) on angiotensin II administration as a potential paracrine culprit mediating early degenerative events in vascular smooth muscle resulting in aortic dissection. Surprisingly, such a short-term dramatic effect was not a consequence of the hypertensive response to angiotensin II, because equal pressor doses of norepinephrine did not cause dissection. Instead, the authors present evidence that, when Nox2 is overexpressed in the endothelium, angiotensin II causes excessive aortic inflammation and remodeling, …