Aberrant antibody responses to oxidized LDL and increased intimal thickening in apoE-/- mice exposed to cigarette smoke.
Cigarette smoking is associated with increased atherosclerosis and intimal thickening, and has immune-suppressive effects. The immune system modulates atherosclerosis and intimal thickening. We hypothesized that detrimental effects of cigarette smoke (CS) involves modulation of the immune response to oxidized low-density lipoprotein (oxLDL). ApoE-/- mice fed Western diet were exposed to CS starting at 20 weeks of age. Control mice were exposed to air. After 5 weeks of CS, mice were subjected to carotid arterial cuffing for 21 days. Intimal thickening was significantly increased in CS mice compared to control (0.050 +/- 0.034 mm(2) versus 0.023 +/- 0.021 mm(2); P < 0.05). Spleen lymphocyte population, cytokine mRNA expression, and total IgM and IgG levels were similar. Anti-MDA oxLDL IgG was reduced by 40% (P < 0.05) in CS mice compared to control. Copper-oxidized LDL IgG antibodies remained unchanged but IgM increased in CS mice, associated with increased intimal thickening. Anti-phosphorylcholine (PC) IgM was also increased in the CS mice, associated with increased intimal thickening. Lymphocyte signaling molecule lymphotoxin beta (LTbeta) expression was significantly decreased in spleens of CS exposed mice. Our results suggest that immune modulation by CS characterized by aberrant antibody responses to oxLDL and reduced LTbeta mRNA expression is associated with increased intimal thickening after arterial cuffing.
Tani
Shigemasa
S
Division of Cardiology, Atherosclerosis Research Center, Cedars-Sinai Medical Center/David Geffen School of Medicine, University of California-Los Angeles, Davis 1064, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
Dimayuga
Paul C
PC
Anazawa
Takeo
T
Chyu
Kuang-Yuh
KY
Li
Hongyan
H
Shah
Prediman K
PK
Cercek
Bojan
B
D000818:Animals; D000906:Antibodies / Q000097:blood*; D000975:Antioxidants / Q000032:analysis; D001057:Apolipoproteins E / Q000172:deficiency; D016516:CD4-CD8 Ratio; D002263:Carboxyhemoglobin / Q000032:analysis; D002339:Carotid Arteries / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008077:Lipoproteins, LDL / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000097:blood; D010767:Phosphorylcholine / Q000276:immunology; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D014028:Tobacco Smoke Pollution; D017539:Tunica Intima / Q000473:pathology*
D000906:Antibodies; D000975:Antioxidants; D001057:Apolipoproteins E; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D014028:Tobacco Smoke Pollution; C099252:oxidized low density lipoprotein; D010767:Phosphorylcholine; D009569:Nitric Oxide; D002263:Carboxyhemoglobin; D002784:Cholesterol