| TITLE: | Defensin stimulates the binding of lipoprotein (a) to human vascular endothelial and smooth muscle cells. | ||||||
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| AUTHOR: | Higazi AA; Lavi E; Bdeir K; Ulrich AM; Jamieson DG; Rader DJ; Usher DC; Kane W; Ganz T; Cines DB | ||||||
| AUTHOR AFFILIATION: | Department of Pathology, University of Pennsylvania Medical Center, Philadelphia, USA. | ||||||
| SOURCE: | Blood 1997 Jun 15;89(12):4290-8 | ||||||
| NLM CIT. ID: | 97335956 | ||||||
| ABSTRACT: | 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. | ||||||
| MAIN MESH SUBJECTS: |
Blood Proteins/ANALYSIS/*PHARMACOLOGY/SECRETION Endothelium, Vascular/*DRUG EFFECTS/METABOLISM Lipoprotein(a)/*METABOLISM Muscle, Smooth, Vascular/*DRUG EFFECTS/METABOLISM | ||||||
| ADDITIONAL MESH SUBJECTS: |
Adult Aged Aged, 80 and over Aortic Diseases/METABOLISM Apolipoproteins/ANALYSIS Atherosclerosis/ETIOLOGY/METABOLISM Cells, Cultured Cerebral Arteries/CHEMISTRY Coronary Arteriosclerosis/METABOLISM/PATHOLOGY Endocytosis/DRUG EFFECTS Female Human Leukocytes/SECRETION Macromolecular Systems Male Middle Age Protein Binding/DRUG EFFECTS Stimulation, Chemical Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Umbilical Veins Vasculitis/COMPLICATIONS | ||||||
| PUBLICATION TYPES: | JOURNAL ARTICLE | ||||||
| LANGUAGE: | Eng | ||||||
| REGISTRY NUMBERS: |
0 (apolipoprotein Lp(a+)) 0 (defensins) 0 (Apolipoproteins) 0 (Blood Proteins) 0 (Lipoprotein(a)) 0 (Macromolecular Systems) | ||||||