Apolipoprotein A-1-derived amyloid in atherosclerotic plaques of the human aorta.
Previous studies have shown that the amyloid localized to the aortic intima may be a biochemical entity different from other forms of localized amyloid. The amyloid fibril protein in one patient studied consisted of an N-terminal fragment of apolipoprotein A-1 (apo A-1). Since this patient was later shown to carry a missense mutation in the apo A-1 gene, leading to a deletion at position 107 of the mature protein, the question remained whether wild-type apo A-1 is amyloidogenic. In autopsy specimens from the thoracic aorta from 69 individuals, intimal atherosclerotic plaque-related amyloid was present in 11 cases (16%) and amyloid outside plaques in 37 cases (54%). The immunoreactivity of amyloid localized to the aortic intima was evaluated with the aid of antisera against N-terminal segments of apo A-1. The amyloid in association with atherosclerotic plaques was positively labelled by immunohistochemistry. The amyloid fibril protein from one patient, previously shown not to carry any mutation in the apo A-1 gene, was purified and shown by amino acid sequence analysis to be of apo A-1 nature. The result shows that wild-type apo A-1 is amyloidogenic and gives rise to a common localized form of amyloid associated with atherosclerosis.
Mucchiano
G I
GI
Division of Molecular and Immunological Pathology, Linköping University, Sweden.
Häggqvist
B
B
Sletten
K
K
Westermark
P
P
D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000737:chemistry*; D001011:Aorta / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008875:Middle Aged; D020539:Sequence Analysis, Protein; D017539:Tunica Intima / Q000378:metabolism
D000682:Amyloid; D016632:Apolipoprotein A-I