Conflicting mechanisms of AT2 cardioprotection revealed

This editorial refers to ‘The angiotensin II type 2 receptor activates flow-mediated outward remodelling through T cells-dependent interleukin-17 production’, by A. Caillon et al., pp. 515–525. Coronary artery disease is a major cause of mortality in the developed world due to the death of cardiac muscle because of inadequate delivery of oxygen-rich blood. The knowledge gained from basic research on preventing cardiac muscle loss by enhancing the formation of new arteries in the heart (angiogenesis) has not translated to date into clinical benefit. An alternative, perhaps more promising strategy is to foster arteriogenesis, which refers to the remodelling of pre-existing collateral resistance vessels to form arteries that effectively bypass major arterial obstructions.1–4 Indeed, a positive correlation is observed between the number of collateral arteries and extent of their coverage and survival in patients with coronary artery disease,4 although similar remodelling if it occurs in an atherosclerotic artery may increase the propensity for plaque destabilization and rupture.5 Notably, several pro-arteriogenic mechanisms or treatments promote atherosclerotic plaque development and instability, while conversely anti-atherogenic factors may inhibit arteriogenesis.6 The structural changes in the vessel wall that occur with arteriogenesis reflect outward remodelling, which is an increase in lumen diameter and relative reduction in wall thickness. The primary stimulus that drives arteriogenesis is sheer stress due to increases in blood flow and entails activation of endothelial cells (EC), basal membrane degradation, infiltration of immune cells, proliferation of vascular smooth muscle cells (VSMC), and changes in the extracellular matrix.1 Specific factors involved in the outward remodelling include nitric oxide (NO), vascular endothelial growth factor, chemokine (C-C) motif ligand 2 (CCL2; also known as monocyte chemoattractant protein 1 …