Atherin: a newly identified, lesion-specific, LDL-binding protein in human atherosclerosis.
Prolonged retention of LDL in focal, atherosclerosis-prone areas of arteries is a primary event in atherogenesis. To determine whether unrecognized LDL-binding proteins participate in this process, we generated a cDNA expression library from deendothelialized rabbit aorta, a model for early atherosclerosis that shows striking focal LDL retention in healing lesions. Library screening identified a previously unknown, highly conserved, 56kDa LDL-binding protein that we call atherin. Confocal microscopy of human arteries shows that atherin is present only in atherosclerotic lesions, not in normal intima. Within lesions, atherin is found both in the extracellular compartment and within foam cells. Essentially all extracellular atherin, as well as atherin within foam cells, co-localizes with LDL across the entire spectrum of human disease, from early lesions to advanced plaques. Our results suggest that focal arterial LDL accumulation may be initiated and maintained by binding between LDL and atherin, and that atherin may play a central role in atherogenesis by immobilizing LDL in the arterial wall.
Lees
Ann M
AM
Boston Heart Foundation, 203 Clinton Road, Brookline, MA 02445-5838, USA. amlees@mit.edu
Deconinck
Anne E
AE
Campbell
Bruce D
BD
Lees
Robert S
RS
D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001012:Aorta, Abdominal / Q000473:pathology / Q000502:physiology; D001013:Aorta, Thoracic / Q000473:pathology / Q000502:physiology; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008078:Cholesterol, LDL / Q000378:metabolism*; D005487:Foam Cells / Q000473:pathology; D015723:Gene Library; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D008969:Molecular Sequence Data; D011817:Rabbits; D011973:Receptors, LDL / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
D051376:Actin-Related Protein 2-3 Complex; D000906:Antibodies; D008078:Cholesterol, LDL; D011973:Receptors, LDL; C506800:SAMD1 protein, human; C488100:TXLNA protein, human; D033921:Vesicular Transport Proteins