Dexamethasone inhibits macrophage accumulation after balloon arterial injury in cholesterol fed rabbits.
Macrophages play a critical role in the development and progression of atherosclerosis. This study was designed to examine the effect of the glucocorticoid, dexamethasone, (Dex), on macrophage accumulation after acute arterial injury. Twenty New Zealand white rabbits were fed a 2% cholesterol, 6% peanut oil, rabbit chow diet for one month prior to bilateral balloon dilatation of the femoral arteries. Ten rabbits received Dex (1 mg/kg, im.) the day before and then daily for 7 days after arterial injury; control rabbits received vehicle only. Seven days after injury, Dex treatment resulted in a 96% and 77% reduction (P < 0.002) in the mean number of macrophages accumulating in the intima and media, respectively. This effect was apparently not due to a reduction in the number of circulating monocytes or to the ability of monocytes from Dex treated animals to adhere to endothelium or migrate in response to a chemotactic signal, determined in vitro under static conditions. It was associated with a 61% reduction in monocyte chemoattractant protein-1 (MCP-1) antigen (P < 0.004) in the injured arterial wall (media+intima). Glucocorticoids may be useful in attenuating the inflammatory response and subsequent foam-cell accumulation after arterial injury.
The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY, 10029, USA.
M
M
Poon
S D
SD
Gertz
J T
JT
Fallon
P
P
Wiegman
J W
JW
Berman
I J
IJ
Sarembock
M B
MB
Taubman
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000139:chemically induced / Q000473:pathology / Q000601:surgery*; D002404:Catheterization / Q000009:adverse effects*; D002448:Cell Adhesion / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D002791:Cholesterol, Dietary / Q000633:toxicity*; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D004036:Diet, Atherogenic; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005263:Femoral Artery / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006965:Hyperplasia; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D014947:Wounds and Injuries / Q000188:drug therapy
D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D002791:Cholesterol, Dietary; D003907:Dexamethasone