| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Gill Heart Institute, Division of Hematology/Oncology, University of Kentucky, Lexington, KY 40536
Division of Cardiovascular Medicine, and Blood and Marrow Transplant Program, Division of Hematology/Oncology, University of Kentucky, Lexington, KY 40536
Pfizer Global Research and Development, Ann Arbor Laboratories, Cardiovascular Therapeutics, 2800 Plymouth Road, Ann Arbor, MI 48105
2 To whom correspondence should be addressed. e-mail: adaugh{at}uky.edu
Class A scavenger receptors (SR-A) have been implicated in the atherogenic process, although there have been conflicting reports as to their specific effect on the development of lesions. In part, this discord may arise because of the variable contribution of SR-A in the several cell types known to express this protein. To determine the effects of macrophage-specific SR-A expression in the atherogenic process, transgenic mice were created using the chicken lysozyme (lyso) promoter to drive expression of bovine SR-A (bSR-A). To express this gene in an atherosclerosis-susceptible strain, bone marrow cells from transgenic and non-transgenic littermates were used to repopulate lethally-irradiated female LDL receptor (LDLr)-/- mice. Following hematopoietic engraftment, mice were placed on a diet enriched in saturated fat and cholesterol. After 8 weeks, there was a modest, but statistically significant reduction in serum total cholesterol in LDLr-/- mice repopulated with lyso-bSR-A transgenic cells, due to decreased LDL-cholesterol. The extent of atherosclerosis was reduced in both cross-sectional analysis of the aortic root and en face analysis of the intimal surface of the aortic arch. In addition to changes in atherosclerosis, lyso-bSR-A repopulated LDLr-/- mice had a marked increase (3.6x) in spleen weights and a disruption of spleen white pulp formation.
Therefore, macrophage-specific overexpression of SR-A resulted in reduced atherosclerosis in two vascular beds, reduced serum cholesterol concentrations, and changed the morphology of the spleen.
Abbreviations: BMT, bone marrow transplant; lyso, lysozyme; SR-A, class A scavenger receptors
Supplementary key words bone marrow transplantation • low density lipoprotein • immune function
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  D. M. Okamura, J. M. Lopez-Guisa, K. Koelsch, S. Collins, and A. A. Eddy Atherogenic scavenger receptor modulation in the tubulointerstitium in response to chronic renal injury Am J Physiol Renal Physiol, August 1, 2007; 293(2): F575 - F585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Bostrom, B. B. Boyanovsky, C. T. Jordan, M. P. Wadsworth, D. J. Taatjes, F. C. de Beer, and N. R. Webb Group V Secretory Phospholipase A2 Promotes Atherosclerosis: Evidence From Genetically Altered Mice Arterioscler. Thromb. Vasc. Biol., March 1, 2007; 27(3): 600 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-L. Lin, W. J. S. de Villiers, B. Garvy, S. R. Post, T. R. Nagy, F. F. Safadi, M. C. Faugere, G. Wang, H. H. Malluche, and J. P. Williams The Effect of Class A Scavenger Receptor Deficiency in Bone J. Biol. Chem., February 16, 2007; 282(7): 4653 - 4660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Cassis, D. L. Rateri, H. Lu, and A. Daugherty Bone Marrow Transplantation Reveals That Recipient AT1a Receptors Are Required to Initiate Angiotensin II-Induced Atherosclerosis and Aneurysms Arterioscler. Thromb. Vasc. Biol., February 1, 2007; 27(2): 380 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Moore and M. W. Freeman Scavenger Receptors in Atherosclerosis: Beyond Lipid Uptake Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1702 - 1711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ricci, G. Sumara, I. Sumara, I. Rozenberg, M. Kurrer, A. Akhmedov, M. Hersberger, U. Eriksson, F. R. Eberli, B. Becher, et al. Requirement of JNK2 for Scavenger Receptor A-Mediated Foam Cell Formation in Atherogenesis Science, November 26, 2004; 306(5701): 1558 - 1561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Whitman, D. L. Rateri, S. J. Szilvassy, W. Yokoyama, and A. Daugherty Depletion of Natural Killer Cell Function Decreases Atherosclerosis in Low-Density Lipoprotein Receptor Null Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2004; 24(6): 1049 - 1054. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
