P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits before intimal accumulation of macrophages and T lymphocytes.
The accumulation of monocyte/macrophages and T lymphocytes in arterial intima is a hallmark of early atherogenesis. To investigate the temporal relationships between endothelial expression of adhesion molecules (eg, P-selectin and vascular cell adhesion molecule-1 [VCAM-1]) and intimal accumulation of macrophages and T lymphocytes, immunostaining was performed by using serial frozen sections from intercostal branch points of thoracic aortas of New Zealand White rabbits that had been fed a 0.3% cholesterol diet. After 1 week of cholesterol feeding, neither macrophages nor T lymphocytes were detected, although endothelial expression of P-selectin and VCAM-1 was observed. After 3 weeks, macrophages were detectable in 75% and T lymphocytes were present in 25% of the rabbits. Expression of P-selectin and VCAM-1 was sustained until 10 weeks. Infiltration of T lymphocytes was restricted in areas in which macrophages were accumulated and did not appear to precede macrophage infiltration. E-selectin expression was not detectable before accumulation of mononuclear leukocytes; however, very few endothelial cells covering foam cell lesions expressed E-selectin after 6 weeks. Similar results were obtained in Watanabe heritable hyperlipidemic rabbits aged 1, 2, and 3 months. Taken together, localized expression of P-selectin and VCAM-1 may play a key role in the initial recruitment of macrophages and T lymphocytes in early atherogenesis.
Sakai
A
A
Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, Japan.
Kume
N
N
Nishi
E
E
Tanoue
K
K
Miyasaka
M
M
Kita
T
T
D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology*; D002791:Cholesterol, Dietary / Q000494:pharmacology; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004731:Endotoxins / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000378:metabolism* / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D019007:P-Selectin / Q000378:metabolism*; D011817:Rabbits; D013601:T-Lymphocytes / Q000473:pathology; D017539:Tunica Intima / Q000473:pathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D002791:Cholesterol, Dietary; D019040:E-Selectin; D004731:Endotoxins; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1