scholarly journals Oxidized high-density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 1962-1971 ◽  
Author(s):  
Manojkumar Valiyaveettil ◽  
Niladri Kar ◽  
Mohammad Z. Ashraf ◽  
Tatiana V. Byzova ◽  
Maria Febbraio ◽  
...  

Numerous studies have reported the presence of oxidatively modified high-density lipoprotein (OxHDL) within the intima of atheromatous plaques as well as in plasma; however, its role in the pathogenesis of thrombotic disease is not established. We now report that OxHDL, but not native HDL, is a potent inhibitor of platelet activation and aggregation induced by physiologic agonists. This antithrombotic effect was concentration and time dependent and positively correlated with the degree of lipoprotein oxidation. Oxidized lipoproteins are known ligands for scavenger receptors type B, CD36 and scavenger receptor B type I (SR-BI), both of which are expressed on platelets. Studies using murine CD36−/− or SR-BI−/− platelets demonstrated that the antithrombotic activity of OxHDL depends on platelet SR-BI but not CD36. Binding to SR-BI was required since preincubation of human and murine platelets with anti–SR-BI blocking antibody abrogated the inhibitory effect of OxHDL. Agonist-induced aggregation of platelets from endothelial nitric oxide synthase (eNOS)−/−, Akt-1−/−, and Akt-2−/− mice was inhibited by OxHDL to the same degree as platelets from wild-type (WT) mice, indicating that the OxHDL effect is mediated by a pathway different from the eNOS/Akt pathway. These novel findings suggest that contrary to the prothrombotic activity of oxidized low-density lipoprotein (OxLDL), HDL upon oxidation acquires antithrombotic activity that depends on platelet SR-BI.

Endocrinology ◽  
1999 ◽  
Vol 140 (6) ◽  
pp. 2494-2500 ◽  
Author(s):  
Per-Arne Svensson ◽  
Magnus S. C. Johnson ◽  
Charlotte Ling ◽  
Lena M. S. Carlsson ◽  
Håkan Billig ◽  
...  

Abstract Scavenger receptor class B type I (SR-BI) mediates the selective uptake of high density lipoprotein cholesterol. SR-BI is expressed at high levels in the ovary, indicating that it plays a role in the delivery of cholesterol as substrate for steroid hormone production. However, SR-BI also binds anionic phospholipids with high affinity and could therefore be involved in the recognition of apoptotic cells. In this study we have characterized the expression of SR-BI in rat ovarian follicles undergoing atresia. Atretic follicles with cells undergoing apoptosis were identified by in situ DNA end labeling, and SR-BI expression was determined by in situ hybridization and immunohistochemistry. SR-BI was expressed in thecal cells at all stages of follicular development, including atretic follicles, and in corpus luteum. Isolated apoptotic granulosa cells (but not viable granulosa cells) bound annexin V, indicating that they display anionic phospholipids on the cell surface. Transfection of COS-7 cells with an expression vector carrying the rat SR-BI complementary DNA resulted in increased binding to apoptotic granulosa cells (46 ± 2% of the SR-BI-expressing cells bound at least one granulosa cell compared with 24 ± 3% for the mock-transfected cells; P < 0.0001), whereas the binding to viable granulosa cells was unchanged. Apoptotic granulosa cells also bound to isolated thecal shells. We conclude that thecal cells of both nonatretic and atretic follicles express SR-BI. The location of SR-BI expression in the ovary supports a role of this receptor in the uptake of high density lipoprotein cholesterol. In addition, our data suggest that SR-BI mediates the recognition of apoptotic granulosa cells by the surrounding thecal cells and that it therefore may play a role in the remodeling of atretic follicles to secondary interstitial cells.


2000 ◽  
Vol 275 (28) ◽  
pp. 21262-21271 ◽  
Author(s):  
Kalliopi N. Liadaki ◽  
Tong Liu ◽  
Shangzhe Xu ◽  
Brian Y. Ishida ◽  
Philippe N. Duchateaux ◽  
...  

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 1749-1750 ◽  
Author(s):  
Meinrad Gawaz

Scavenger receptors are increasingly recognized as playing a critical role in atherothrombosis.1 A new study presented by Valiyaveettil and colleagues in this issue of Blood demonstrates that oxidatively modified high-density lipoprotein (OxHDL) exhibits potent antiplatelet activity via the platelet scavenger receptor B type I (SR-BI).


2006 ◽  
Vol 98 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Divya Seetharam ◽  
Chieko Mineo ◽  
Andrew K. Gormley ◽  
Linda L. Gibson ◽  
Wanpen Vongpatanasin ◽  
...  

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