title: Normal and oxidized low density lipoproteins accumulate deep in physiologically thickened intima of human coronary arteries.
abstract: Diffuse intimal thickening (DIT) that develops as a physiologic adaptation in the arterial wall has been implicated to have a predilection for atherosclerosis. We histologically investigated the lipid accumulation process in the human coronary DIT by focusing on the localization of normal and oxidized low-density lipoproteins (LDLs). Immunohistochemistry for apolipoprotein B 100 (a major apolipoprotein of LDL) and 8-iso-prostaglandin F(2alpha) (an oxidative product in LDL) showed substantial accumulation of oxidized relative to normal LDLs in the deep layers of DIT (52/139 segments). Subendothelial deposition of normal rather than oxidized LDLs, known as an early event of fatty streak formation, was less frequently found (13/139 segments). In contrast with fibrofatty lesions, lipid accumulation localized deep in DIT was characterized by fine lipid droplets scattered in the preserved tissue and by its association with neither macrophage accumulation nor apoptosis in the constituent cells. On the other hand, the deep intimal location of lipid accumulation clearly coincided with increased type I and type III collagen and elastic fibers but rarely with sulfated proteoglycans including decorin, which were all strongly expressed in advanced lesions. This lipid accumulation was found only in sites with DIT of more than 200 micro m, occasionally extending to the inner media and involving neovessel formation around it. The presence of deep intimal lipid accumulation was associated with reduced endothelium-dependent relaxation to substance P in isolated coronary rings. These results suggest that normal and oxidized LDLs accumulate preferably in the nutritional border zone of established DIT involving local extracellular matrix alterations but independently of inflammatory or apoptotic processes. This may contribute to the functional and morphologic abnormalities seen in human coronary atherogenesis that progresses slowly with age.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University, Graduate School of Medicine, Sendai, Japan.
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Fukuchi
authors.forename: Jun
authors.initials: J
authors.lastname: Watanabe
authors.forename: Koji
authors.initials: K
authors.lastname: Kumagai
authors.forename: Shigeo
authors.initials: S
authors.lastname: Baba
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shinozaki
authors.forename: Masahito
authors.initials: M
authors.lastname: Miura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kagaya
authors.forename: Kunio
authors.initials: K
authors.lastname: Shirato
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D001344:Autopsy; D003331:Coronary Vessels / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein