Guzik and Touyz Oxidation and Inflammation in Vascular Aging 661 and endothelium. 22 Perivascular fibrosis is greatly dependent on immune cells because it is prevented in RAG1−/− mice lacking mature T and B cells. 21 This process, although inflammatory in its nature, seems to be initiated by oxidative stress. In line with this, therapies which are known to reduce oxidative stress, such as mineralocorticoid antagonists, or angiotensin-converting enzyme inhibitors, are known to improve vascular stiffness acceleration. 23 One of the key novel mechanisms linking oxidative stress to fibrosis involves small GTP-binding protein dissociation stimulator. Its upregulation by statins results in Rac1 degradation and reduced oxidative stress24 and may reduce cardiac and possibly vascular fibrosis. Accelerated aging in hypertension is observed in both the micro-and macrocirculation, with important cross talk between large vessels and microvasculature. 25 Increased BP, attributed to dysfunction and remodeling of small arterioles, plays a role in inducing arterial stiffness. 25, 26 As discussed above, oxidative stress and inflammation are essential components affecting both micro-and macrovascular function, initiating a vicious circle between increased BP, vascular remodeling, stiffness, and continued hypertension and its atherosclerotic complications. 15, 25, 26