Angiotensin II to macrophage: will you polarize? And when?

摘要

an activated immune system is increasingly regarded as a major contributor to hypertension in various animal models (spontaneously hypertensive rats, angiotensin II-induced hypertension, and salt-dependent hypertension to name a few). For example, activation of T cells, dendritic cells, and mono-cytes/macrophages has been observed in sympathetic outflow-dependent hypertension (8, 11), in conductance vessels (2, 3), in the kidney (1, 10, 14), and in the salt-challenged interstitium (7,17). Also, end-organ damage seen in arterial hypertension is attributed significantly to activated immune cells [for review, see McMaster et al. (9)]. Attenuating an inflammatory response has been shown to reduce sequela of hypertension like cardiac dysfunction (6), hypertensive kidney disease (12), and aortic aneurysm formation (15). Importantly, in many of these observations, angiotensin II is directly involved or at least implicated.In particular, monocytes and macrophages have been identified as important contributors to vascular inflammation and hypertension elicited by angiotensin II. Mice that lack the mature macrophages because of macrophage-colony stimulating factor deficiency have a significantly blunted response to angiotensin II with less vascular oxidative stress, endothelial dysfunction, and arterial hypertension (2). Ablation of ly-sozyme-M+ myelomonocytic cells attenuates almost all consequences of angiotensin II, including vascular remodeling (16). Inflammatory monocytes typically express high levels of chemokine (C-C motif) receptor 2 (CCR2), the receptor for the monocyte chemoattractant protein 1 [chemokine (C-C motif) ligand 2]. CCR2-deficient mice have been reported to be protected from angiotensin II-induced vascular remodeling (4). Interestingly, CCR2~/~ mice are protected from angiotensin II-induced abdominal aortic aneurysm, a late sequel of hypertension (15). However, it has been unclear whether inflammatory monocytes/macrophages undergo polarization or further (de)differentiation under continuous exposure to angiotensin II to exert these complex physiological roles.