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Intracranial arteries of human fetuses are more resistant to hypercholesterolemia-induced fatty streak formation than extracranial arteries.
- Source :
-
Circulation [Circulation] 1999 Apr 20; Vol. 99 (15), pp. 2003-10. - Publication Year :
- 1999
-
Abstract
- 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.<br />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.<br />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.
- Subjects :
- Abortion, Spontaneous
Adult
Aorta, Abdominal enzymology
Aorta, Abdominal pathology
Arteriosclerosis embryology
Arteriosclerosis pathology
Carotid Artery, Common enzymology
Carotid Artery, Common pathology
Catalase analysis
Cerebral Arteries enzymology
Cerebral Arteries pathology
Female
Fetal Diseases pathology
Free Radicals
Gestational Age
Glutathione Peroxidase analysis
Humans
Immunity, Innate
Infant, Newborn
Infant, Premature
Lipid Peroxidation
Lipids analysis
Male
Organ Specificity
Pregnancy
Pregnancy Complications blood
Superoxide Dismutase analysis
Aorta, Abdominal embryology
Arteriosclerosis etiology
Carotid Artery, Common embryology
Cerebral Arteries embryology
Fetal Diseases etiology
Hypercholesterolemia physiopathology
Pregnancy Complications physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4539
- Volume :
- 99
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 10209005
- Full Text :
- https://doi.org/10.1161/01.cir.99.15.2003