Function of scavenger receptor class A type I/II is not important for smooth muscle foam cell formation.
Macrophages (MPhi) and smooth muscle cells (SMC) are transformed into foam cells by massive accumulation of modified lipoproteins during atherogenesis. It is known that class AI/II scavenger receptors participate in the foam cell formation of MPhi. The mechanism of lipid accumulation in SMC is however unknown. Therefore, we investigated if class AI/II scavenger receptors mediate the uptake of modified lipoproteins in SMC. Additionally, we examined the influence of MPhi and proinflammatory cytokines in this process. Our flow cytometric experiments revealed significant uptake of DiI-AcLDL in SMC. This uptake was markedly enhanced by IL-1alpha and TNF-alpha, whereas cocultured MPhi decreased the uptake of DiI-AcLDL in SMC. Competition and blocking experiments were performed to enlighten the role of class AI/II scavenger receptors. The competition experiments showed that surplus NatLDL, a ligand not known to interact with class AI/II scavenger receptors, caused a drastically decreased uptake of DiI-AcLDL in SMC. Additionally, blocking of class AI/II scavenger receptors with antibody 2F8 did not influence the uptake of DiI-AcLDL in SMC. Furthermore, fluorescence microscopic double staining of human coronary arteries with early, intermediate and advanced atherosclerotic lesions showed no colocalization of class AI scavenger receptors with SMC. These results indicate that class AI/II scavenger receptors play only a minor role in the uptake of modified lipoproteins in SMC. We suggest that SMC foam cell formation is mainly mediated by other receptors than class AI/II scavenger receptors.
Luechtenborg
Birgit
B
Leibniz-Institute for Arteriosclerosis Research, University Hospital of Muenster, Germany.
Hofnagel
Oliver
O
Weissen-Plenz
Gabriele
G
Severs
Nick J
NJ
Robenek
Horst
H
D000818:Animals; D003331:Coronary Vessels / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005487:Foam Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D051117:Scavenger Receptors, Class A / Q000378:metabolism*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D053582:Interleukin-1alpha; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D051117:Scavenger Receptors, Class A; D014409:Tumor Necrosis Factor-alpha; C032629:acetyl-LDL