| Intracranial arteries of human fetuses are more resistant to hypercholesterolemia-induced fatty streak formation than extracranial arteries. | |
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MedLine Citation:
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PMID: 10209005 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Atherosclerotic lesions in intracranial arteries occur later and are less extensive than in extracranial arteries. To investigate potential mechanisms responsible for this difference, in particular the atherogenic response to hypercholesterolemia and LDL oxidation, we compared the extent of fatty streak formation and the composition of these very early lesions in intracranial arteries of human fetuses from normocholesterolemic and hypercholesterolemic mothers with those in extracranial arteries. METHODS AND RESULTS: Lesions were quantified by computer-assisted image analysis of 30 oil red O-stained sections, each from the middle cerebral, basilar, and common carotid arteries and the abdominal aorta of human fetuses (spontaneous abortions and premature newborns who died within 12 hours of birth; both of fetal age 6.2+/-1.3 months) from 43 hypercholesterolemic mothers and 34 normocholesterolemic mothers. Macrophages, apolipoprotein B, and 2 epitopes of oxidized LDL in lesions were determined immunocytochemically. Activities of superoxide dismutase, catalase, and glutathione peroxidase in the arterial wall were also determined. Lesion numbers and sizes were dramatically greater in the abdominal aorta (area of the largest lesion per section: 66.5+/-10.9 x10(3) microm2) and the carotid (11. 6+/-5.3 x10(3) microm2) than in the basilar and middle cerebral artery (0.4+/-0.1 and 0.8+/-0.2 x10(3) microm2, respectively; P<0. 0001). Hypercholesterolemia resulted in a significant increase of lesion size in extracranial arteries but only a marginal increase in intracranial arteries. In analogy, hypercholesterolemia induced a much greater increase in the intimal presence of macrophages, apolipoprotein B, and oxidized LDL (oxidation-specific epitopes) in extracranial than in intracranial arteries. Immunocytochemistry did not indicate that lesions of intracranial arteries contain relatively less oxidized LDL than similar-size lesions of extracranial arteries. Activities of Mn-superoxide dismutase but not of Zn-superoxide dismutase, catalase, or glutathione peroxidase were significantly higher in both intracranial arteries. CONCLUSIONS: Exposure to hypercholesterolemia during fetal development results in extensive formation of fatty streaks in extracranial but not intracranial arteries. The fact that such a difference in lesion formation occurs in the absence of many other atherogenic risk factors found later in life suggests that differences in the atherogenic response to hypercholesterolemia are an important contributor to the slower onset of the disease in intracranial vessels in adults. Fetal arteries may allow elucidation of the mechanisms responsible, for example, better protection of intracranial arteries against free radical-mediated atherogenic processes. |
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Authors:
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C Napoli; J L Witztum; F de Nigris; G Palumbo; F P D'Armiento; W Palinski |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Circulation Volume: 99 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 1999 Apr |
Date Detail:
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Created Date: 1999-04-30 Completed Date: 1999-04-30 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2003-10 Citation Subset: AIM; IM |
Affiliation:
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Department of Clinical and Experimental Medicine, Federico II University of Naples, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Abortion, Spontaneous Adult Aorta, Abdominal / embryology*, enzymology, pathology Arteriosclerosis / embryology, etiology*, pathology Carotid Artery, Common / embryology*, enzymology, pathology Catalase / analysis Cerebral Arteries / embryology*, enzymology, pathology Female Fetal Diseases / etiology*, pathology Free Radicals Gestational Age Glutathione Peroxidase / analysis Humans Hypercholesterolemia / physiopathology* Immunity, Innate Infant, Newborn Infant, Premature Lipid Peroxidation Lipids / analysis Male Organ Specificity Pregnancy Pregnancy Complications / blood, physiopathology* Superoxide Dismutase / analysis |
| Grant Support | |
ID/Acronym/Agency:
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HL-56989/HL/NHLBI NIH HHS; M01-RR00827/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Free Radicals; 0/Lipids; EC 1.11.1.6/Catalase; EC 1.11.1.9/Glutathione Peroxidase; EC 1.15.1.1/Superoxide Dismutase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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