Elevated expression of monocyte chemoattractant protein 1 by vascular smooth muscle cells in hypercholesterolemic primates.
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 monocyte-like 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.
Yu
X
X
Department of Oral Biology, Boston University Medical Center, MA 02118.
Dluz
S
S
Graves
D T
DT
Zhang
L
L
Antoniades
H N
HN
Hollander
W
W
Prusty
S
S
Valente
A J
AJ
Schwartz
C J
CJ
Sonenshein
G E
GE
D000818:Animals; D015152:Blotting, Northern; D002339:Carotid Arteries / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary; D004036:Diet, Atherogenic; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008252:Macaca fascicularis; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D002791:Cholesterol, Dietary; D012333:RNA, Messenger; D012313:RNA; D002784:Cholesterol