This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jerome, W. G. Articles by Lewis, J. C. Search for Related Content PubMed PubMed Citation Articles by Jerome, W. G. Articles by Lewis, J. C.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:654-664.)
© 1997 American Heart Association, Inc.

Articles

Cellular Dynamics in Early Atherosclerotic Lesion Progression in White Carneau Pigeons

Spatial and Temporal Analysis of Monocyte and Smooth Muscle Invasion of the Intima

W. Gray Jerome; ; Jon C. Lewis

From the Department of Pathology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC.

Correspondence to W. Gray Jerome, PhD, Department of Pathology, Bowman Gray School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1092.

Abstract The early stages of atherosclerosis are characterized by macrophage invasion of the intimal space and proliferation of smooth muscle cells (SMCs). In this study, we characterize the timing and location of each of these processes. Dividing cells of the developing lesions were labeled with [³H]thymidine at different times during lesion progression. Comparable stages of lesion development were analyzed, with the only variable being the length of time between labeling and necropsy. In this way, the mechanism by which lesion composition changes could be inferred from changes in the distribution of label over time. When cells were labeled just before necropsy, serial sections showed monocyte influx predominantly occurring at lesion edges and resulting in a labeling index of 27%. Near the lesion edge, medial SMCs were not stimulated to proliferate. In contrast, in more central areas of the lesion, monocyte influx and intimal SMC proliferation were minimal. Medial SMC proliferation in central regions, however, was high, with a labeling index of 20% in the upper media. Over time, proliferating medial SMCs migrated into the intimal lesion but did not migrate laterally to any great extent. This migration pattern maintained precise subdomains during lesion development, with each domain representing a different stage of lesion development. The edge of lesions thus represents very early events, central regions indicate later events, and intermediate regions provide information about stages between these extremes.

Key Words: atherosclerosis • atherogenesis • smooth muscle • macrophages

This article has been cited by other articles:

				A. Daugherty, N. R. Webb, D. L. Rateri, and V. L. King Thematic review series: The Immune System and Atherogenesis. Cytokine regulation of macrophage functions in atherogenesis J. Lipid Res., September 1, 2005; 46(9): 1812 - 1822. [Abstract] [Full Text] [PDF]

				P. G. Yancey and W. G. Jerome Lysosomal cholesterol derived from mildly oxidized low density lipoprotein is resistant to efflux J. Lipid Res., March 1, 2001; 42(3): 317 - 327. [Abstract] [Full Text]

				P. G. Yancey and W. G. Jerome Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species J. Lipid Res., July 1, 1998; 39(7): 1349 - 1361. [Abstract] [Full Text]

				W. G. Jerome, C. Cash, R. Webber, R. Horton, and P. G. Yancey Lysosomal lipid accumulation from oxidized low density lipoprotein is correlated with hypertrophy of the Golgi apparatus and trans-Golgi network J. Lipid Res., July 1, 1998; 39(7): 1362 - 1371. [Abstract] [Full Text]