Angiotensin II and leukocyte trafficking: New insights for an old vascular mediator. Role of redox-signaling pathways

Inflammation and activation of the immune system are key molecular and cellular events in the pathogenesis of cardiovascular diseases, including atherosclerosis, hypertension-induced target-organ damage, and abdominal aortic aneurysm. Angiotensin II (Ang-II) is the main effector peptide hormone of the renin-angiotensin system. Beyond its role as a potent vasoconstrictor and regulator of blood pressure and fluid homeostasis, Ang-II is intimately involved in the development of vascular lesions in cardiovascular diseases through the activation of different immune cells. The migration of leukocytes from circulation to the arterial subendothelial space is a crucial immune response in lesion development that is mediated through a sequential and coordinated cascade of leukocyte-endothelial cell adhesive interactions involving an array of cell adhesion molecules present on target leukocytes and endothelial cells and the generation and release of chemoattractants that activate and guide leukocytes to sites of emigration. In this review, we outline the key events of Ang-II participation in the leukocyte recruitment cascade, the underlying mechanisms implicated, and the corresponding redox-signaling pathways. We also address the use of inhibitor drugs targeting the effects of Ang-II in the context of leukocyte infiltration in these cardiovascular pathologies, and examine the clinical data supporting the relevance of blocking Ang-II-induced vascular inflammation.