Atherosclerosis is marked by an overt inflammatory infiltrate, with enhanced recruitment of monocytes/macrophages observed in both human and experimental atherosclerosis. We previously determined that monocyte chemoattractant protein 1 (MCP-1) accounts for virtually all of the chemotactic activity produced by vascular (aortic) smooth muscle cells in culture. We now report that arteries from a primate model of atherosclerosis with dietary-induced hypercholesterolemia exhibit increased levels of MCP-1 mRNA expression in vivo, whereas their normal counterparts demonstrate minimal MCP-1 expression. Furthermore, immunohistochemistry and in situ hybridization clearly indicate that the expression of MCP-1 protein and mRNA is in the smooth muscle cells of the medial layer of the artery and in monocytelike and smooth muscle-like cells found in the overlying intimal lesion. These studies indicate that one of the responses to dietary hypercholesterolemia is the expression of MCP-1 by vascular smooth muscle cells. This expression, when augmented with other cellular and molecular factors, could significantly contribute to the recruitment of monocytes/macrophages to the vessel wall.Atherosclerosis is a multistage disease involving invasion of the intima by smooth muscle cells (SMCs) from the media, followed by SMC proliferation and production of an extensive insoluble matrix including such connective tissue components as collagens, elastin, and proteoglycans (1). The two major lesions seen are the fatty streak and the atheromatous or fibrotic plaque. Evidence suggests that fatty streaks, seen in childhood, may progress to fibrotic lesions in adults. Both types of lesions are typified by macrophage invasion (2). Factors released by the macrophage have been shown to influence SMC migration, proliferation, and connective tissue gene expression (3-5). Thus a renewed appreciation of the role of the inflammatory process in coronary arteriosclerosis has emerged.Monocyte chemoattractant protein 1 (MCP-1) is a monomeric polypeptide that migrates in a gel with an estimated molecular mass of 9-15 kDa (6, 7). The various forms of MCP-1 result from differences in O-linked glycosylation and do not affect chemotactic activity (8, 9). Unlike other chemoattractants, MCP-1 is relatively specific for monocytes. Lymphocytes and polymorphonuclear leukocytes lack MCP-1 receptors and do not respond to MCP-1 (10). Previous in vitro studies have shown that this protein can either be secreted by normal cells such as endothelial cells (11) and SMCs (12) or by many tumor cell lines (6, 13). MCP-1 expression in most normal cell types occurs in response to proinflammatory factors such as interleukin 1, tumor necrosis factor a, and interferon y (11, 14). It has also been shown that minimally modified plasma low density lipoprotein stimulates MCP-1 production by human SMCs and endothelial cells in vitro (15). It has been suggested that macrophage/ monocyte recruitment in atherosclerosis occurs in response to a gradient of chemoattractants released ...

The effects of chronic, untreated hypertension on executive function were investigated in a nonhuman primate model of hypertensive cerebrovascular disease. Executive function was assessed with the Conceptual Set-Shifting Task (CSST). a task adapted from the human Wisconsin Card Sorting Test (WCST). Like the WCST, the CSST requires abstraction of a stimulus set, followed by a series of set shifts. Performance on the CSST by 7 young adult monkeys (Macaca mulatta) with surgically induced hypertension was compared with that of 6 normotensive monkeys. The hypertensive group was significantly impaired relative to the normotensive group in abstraction and set shifting. Although the neural basis of this impairment is unclear, evidence from studies with humans and monkeys suggests that the prefrontal cortex may be the locus for this effect of hypertension.

Background and Purpose: There is substantial clinical, pathological, and experimental evidence that hypertension aggravates atherosclerosis of the extracranial vessels. The present study assesses the effects of hypertension on the development of cerebral atherosclerosis in nonhuman primates fed an atherogenic diet.Methods: The extent and severity of cerebral atherosclerosis were evaluated morphologically, morphometrically, and biochemically in atherosclerotic monkeys with and without hypertension. Atherosclerosis was induced by feeding a hypercholesterolemic diet for 12 months; hypertension was produced by surgical coarctation of the thoracic aorta.Results: At autopsy, gross atherosclerotic lesions of the major cerebral arteries were observed in 15 of 16 atherosclerotic monkeys with hypertension compared with 5 of 16 atherosclerotic animals without hypertension. In the hypertensive-atherosclerotic group, 38.5% of the vessels examined showed gross