Polymorphonuclear Leukocytes May Impair Endothelial Function

Ryo Sugano, Hidehiro Matsuoka, Nobuya Haramaki, Hidekazu Umei, Eiko Murase, Kei Fukami, Shuji Iida, Hisao Ikeda, Tsutomu Imaizumi
2005 Arteriosclerosis, Thrombosis and Vascular Biology  
Objectives-To examine whether polymorphonuclear leukocytes (PMNs) in hypercholesterolemia (HC) are activated to generate large amount of superoxide in vivo and hence impair endothelial function and, if so, whether statins, which possess anti-inflammatory properties, may restore PMN-mediated endothelial dysfunction. Methods and Results-At baseline, subjects with HC showed impaired endothelial function (PϽ0.001), estimated by flow-mediated vasodilation of the brachial artery, and increased
more » ... nd increased susceptibility of low-density lipoprotein (LDL) to oxidation (PϽ0.0001) compared with control subjects. PMNs obtained from HC produced greater amount of superoxide (PϽ0.0001), showed higher adhesiveness to cultured endothelial cells (HUVECs) (PϽ0.0001), and impaired endothelial nitric oxide synthase (eNOS) Ser 1177 phosphorylation of HUVECs compared with controls (PϽ0.001). Crossover administration of fluvastatin or colestimide for 3 months lowered LDL to the same levels (PϽ0.001 for both). Endothelial function was restored (PϽ0.0001). LDL oxidation (PϽ0.0001) and superoxide release from PMNs (PϽ0.0001) were diminished only in fluvastatin but not in colestimide arm. Fluvastatin attenuated PMN adhesion to HUVECs (PϽ0.0001) and restored eNOS Ser 1177 phosphorylation of HUVECs (PϽ0.001). Conclusion-Statins may improve endothelial function at least in part by inactivating neutrophils independently of LDL reduction. Our results raise a novel concept that polymorphonuclear leukocytes may attack endothelia and play a pivotal role in the pathogenesis of atherosclerosis. (Arterioscler Thromb Vasc Biol. 2005;25:1262-1267.)
doi:10.1161/01.atv.0000163842.91226.ba pmid:15790932 fatcat:myhmguzdx5gg5camdrjcp2vsau