Coronary risk factors, including age, hypertension, diabetes mellitus, hyperlipidemia, and smoking, are associated with enhanced oxidative stress, which is implicated as a potential mechanism for atherogenesis and atherosclerotic cardiovascular diseases. Male sex is one of the well-known cardiovascular risk factors. We tested the hypothesis that oxidative stress is greater in men than in women. Plasma thiobarbituric acid-reactive substances (TBARS) and urinary 8-isoprostaglandin F2alpha (8-iso-PGF2alpha) were measured in 52 young men and 51 age-matched women. The subjects were healthy, were not smokers, and were not taking any medications or vitamins. Age, blood pressure, plasma cholesterol, and glucose did not differ between the groups. Baseline TBARS (2.32 +/- 0.11 [men] versus 1.87 +/- 0.09 [women] nmol/mL, P<0.01) and 8-iso-PGF2alpha (292 +/- 56 [men] versus 164 +/- 25 [women] pg/mg creatinine, P<0.05) were higher in men than in women. Supplementation of antioxidant vitamins for 4 weeks in men produced a significant reduction in TBARS and 8-iso-PGF2alpha by 34% (P<0.01) and 48% (P<0.05), respectively. Plasma superoxide dismutase, catalase, and vitamin E levels were comparable between the groups. Enhanced oxidative stress in men may provide a biochemical link between male sex and atherosclerotic diseases related to oxidative stress.

Abstract-Activated monocytes are present in the arterial walls of hypertensive patients and animals. Monocyte chemoattractant protein-1 (MCP-1), which controls monocyte function through its receptor (CCR2), is implicated in hypertensive inflammatory changes in the arterial wall. The role of CCR2 expression on monocytes in hypertensioninduced vascular remodeling, however, has not been addressed. We hypothesized that CCR2 on monocytes is critical in hypertension-induced vascular inflammation and remodeling. Hypertension was induced by infusion of angiotensin II (Ang II) into wild-type mice, CCR2-deficient (CCR2 Ϫ/Ϫ ) mice, and bone marrow-transferred mice with a leukocyte-selective CCR2 deficiency (BMT-CCR2 Ϫ/Ϫ ). In wild-type mice, Ang II increased CCR2 intensity in circulating monocytes, which was prevented by an Ang II type-1 (AT 1 ) receptor blocker or blunted in AT 1 receptor-deficient mice. Enhanced CCR2 intensity on monocytes was observed in hypertensive patients and rats, and was reduced by treatment with the Ang II receptor blocker, supporting the clinical relevance of the observation in mice. In CCR2Ϫ/Ϫ and BMT-CCR2 Ϫ/Ϫ mice, Ang II-induced vascular inflammation and vascular remodeling (aortic wall thickening and fibrosis) were blunted as compared with control mice. In contrast, Ang II-induced left ventricular hypertrophy developed in CCR2Ϫ/Ϫ and BMT-CCR2 Ϫ/Ϫ mice. The present study suggests that CCR2 expression in monocytes has a critical role in vascular inflammation and remodeling in Ang II-induced hypertension, and possibly in other forms of hypertension. Key Words: vascular remodeling Ⅲ angiotensin II Ⅲ inflammation Ⅲ leukocytes C hronic monocyte-mediated inflammation in arterial walls is observed in hypertensive patients and animals. [1][2][3] Recent clinical studies reported that lowering angiotensin II (Ang II) activity is a practical target of therapy for patients with cardiovascular disease. 4 -6 Ang II mediates reactive oxidative species (ROS) and stimulates the release of cytokines and growth factors (interleukin-6) and the expression of adhesion molecules (vascular cell adhesion molecule-1) and chemokines [monocyte chemoattractant protein-1 (MCP-1)] that mediate arterial wall inflammation. [1][2][3] For example, Ang II can induce monocyte chemotaxis by producing MCP-1 from vascular smooth muscle cells and monocytes through 8 MCP-1 is a C-C chemokine that controls monocyte recruitment to the site of inflammation through its receptor, C-C chemokine receptor (CCR) 2. 9 -11 The MCP-1/CCR2 pathway appears to be involved in the inflammatory aspect of hypertensive artery disease. MCP-1 and CCR2 expression and activity are enhanced in the arterial walls of hypertensive animals. 12,13 Furthermore, activation of the MCP-1/CCR2 pathway induces monocyte-mediated inflammation, as well as production of adhesion molecules, 14 inflammatory cytokines, 15 and tissue factor, 16 and stimulates migration of vascular smooth muscle cells, resulting in neointimal hyperplasia or atherosclerosis. [17][18][19][20] We...

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