Effects of rosiglitazone on native low-density-lipoprotein-induced respiratory burst in circulating monocytes and on the leukocyte-endothelial interaction in cholesterol-fed rats.
Low-density lipoprotein (LDL) has been implicated in the initiation and progression of atherosclerotic vascular disease. But whether LDL can elicit similar effects in the microcirculation remain unexplored. To approach this issue, the hypothesis that LDL promotes oxidative stress in monocytes and results in microvascular inflammation was tested. Native LDL was capable of stimulating respiratory burst in rat monocytes, and this was blocked by BAPTA, cytochalasin B, apocynin, and diphenyliodonium. In monocytes from rats on a high-cholesterol (4%) diet, increased intracellular calcium, actin polymerization, respiratory burst, and surface CD18 expression were found. Concurrently, leukocyte-endothelial interaction was enhanced in the cremaster microcirculation. Rosiglitazone, an insulin-sensitizing agent with antiinflammatory properties, was found to suppress native-LDL-induced actin polymerization and respiratory burst in monocytes. It also improved leukocytes activation and leukocyte-endothelial interaction due to the high cholesterol intake. Hence, native LDL stimulation of monocytes contributed to hypercholesterolemia-associated microvascular inflammation, which could be treated by rosiglitazone.
Lu
Long Sheng
LS
Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan.
Hung
Li Man
LM
Liao
Chang Hui
CH
Wu
Chau Chung
CC
Su
Ming Jai
MJ
D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects*; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D042783:Endothelial Cells / Q000502:physiology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016897:Respiratory Burst / Q000187:drug effects*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D000199:Actins; D002791:Cholesterol, Dietary; D007004:Hypoglycemic Agents; D008077:Lipoproteins, LDL; D045162:Thiazolidinediones; C099252:oxidized low density lipoprotein; D000077154:Rosiglitazone