Molecular biology of atherothrombotic brain infarction.
Because reduced high density lipoproteins may contribute to atherothrombotic brain infarction, we performed molecular biologic and metabolic studies to characterize high density lipoprotein metabolism with respect to its role in reverse cholesterol transport, to clone the high density lipoprotein receptor, and to determine gene polymorphism for apolipoprotein A-I, the major protein of high density lipoprotein, because altered structure may impair reverse cholesterol transport. For high density lipoprotein metabolism measurements, high density lipoprotein 3 was isolated, purified, and labeled with iodine-125. The radiolabeled high density lipoprotein 3 was reinjected, and daily blood samples were taken for 10 days. Synthesis rates and fractional catabolic rates were determined from the specific activities and daily decrements. Preliminary data indicate that stroke-prone individuals' fractional catabolic rates for high density lipoprotein 3 are twice those of normal individuals. Also, the conversion of high density lipoprotein 3 to high density lipoprotein 2 is reduced in these individuals, suggesting that high density lipoprotein may be abnormally processed in individuals prone to atherothrombic brain infarctions. We surveyed more than 100 patients with carotid stenosis using a 2.2-kb probe for the apolipoprotein A-I gene. A subset of these patients displays polymorphism with restriction enzymes SacI or PstI. These preliminary findings suggest that gene polymorphism for apolipoprotein A-I may provide a molecular clue of atherothrombic brain infarction.
Yatsu
F M
FM
Department of Neurology, University of Texas Medical School, Houston 77030.
Kasturi
R
R
Alam
R
R
Kraus
J
J
Rogers
S
S
DeGraba
T
T
D001161:Arteriosclerosis / Q000150:complications / Q000378:metabolism; D002544:Cerebral Infarction / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D002542:Intracranial Embolism and Thrombosis / Q000150:complications / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism*; D008967:Molecular Biology; D011956:Receptors, Cell Surface / Q000235:genetics; D018110:Receptors, Lipoprotein; D012307:Risk Factors
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein