Defensin stimulates the binding of lipoprotein (a) to human vascular endothelial and smooth muscle cells.
There is evidence to suggest that elevated plasma levels of lipoprotein (a) [Lp(a)] represent a risk factor for the development of atherosclerotic vascular disease, but the mechanism by which this lipoprotein localizes to involved vessels is only partially understood. In view of studies suggesting a link between inflammation and atherosclerosis and our previous finding that leukocyte defensin modulates the interaction of plasminogen and tissue-type plasminogen activator with cultured human endothelial cells, we examined the effect of this peptide on the binding of Lp(a) to cultured vascular endothelium and vascular smooth muscle cells. Defensin increased the binding of Lp(a) to endothelial cells approximately fourfold and to smooth muscle cells approximately sixfold. Defensin caused a comparable increase in the amount of Lp(a) internalized by each cell type, but Lp(a) internalized as a consequence of defensin being present was not degraded, resulting in a marked increase in the total amount of cell-associated lipoprotein. Abundant defensin was found in endothelium and in intimal smooth muscle cells of atherosclerotic human cerebral arteries, regions also invested with Lp(a). These studies suggest that defensin released from activated or senescent neutrophils may contribute to the localization and persistence of Lp(a) in human vessels and thereby predispose to the development of atherosclerosis.
Higazi
A A
AA
Department of Pathology, University of Pennsylvania Medical Center, Philadelphia, USA.
Lavi
E
E
Bdeir
K
K
Ulrich
A M
AM
Jamieson
D G
DG
Rader
D J
DJ
Usher
D C
DC
Kane
W
W
Ganz
T
T
Cines
D B
DB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001018:Aortic Diseases / Q000378:metabolism; D001053:Apolipoproteins / Q000032:analysis; D053241:Apoprotein(a); D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000737:chemistry; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology; D023082:Defensins; D004705:Endocytosis / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D017270:Lipoprotein(a) / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D013268:Stimulation, Chemical; D014471:Umbilical Veins; D014657:Vasculitis / Q000150:complications
D001053:Apolipoproteins; D001798:Blood Proteins; D023082:Defensins; D017270:Lipoprotein(a); D046911:Macromolecular Substances; D053241:Apoprotein(a)