Background
C-reactive protein (CRP) is an acute phase plasma protein. An important binding specificity of CRP is for the modified forms of low-density lipoprotein (LDL) in which the phosphocholine-binding sites of CRP participate. CRP, however, does not bind to native LDL.
Methods
We investigated the interaction of CRP with native LDL using sucrose density gradient ultracentrifugation.
Results
We found that the blocking of the phosphocholine-binding sites of CRP with phosphoethanolamine (PEt) converted CRP into a potent molecule for binding to native LDL. In the presence of PEt, CRP acquired the ability to bind to fluid-phase purified native LDL. Because purified native LDL may undergo subtle modifications, we also used whole human serum as the source of native LDL. In the presence of PEt, CRP bound to native LDL in serum also. The effect of PEt on CRP was selective for LDL because PEt-complexed CRP did not bind to high-density lipoprotein in the serum.
Conclusions
The pharmacologic intervention of endogenous CRP by PEt-based compounds, or the use of exogenously prepared CRP-PEt complexes, may turn out to be an effective approach to capture native LDL cholesterol in vivo to prevent the development of atherosclerosis.
ARTICLE
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ETSU researchers identify a compound that may prevent atherosclerosis – A small molecule compound called phosphoethanolamine (PEt) may prevent the development of atherosclerosis. This compound, PEt, acts through a serum protein known as C-reactive protein (CRP). CRP is the same protein whose serum levels, as confirmed by the American Heart Association, correlate with the occurrence of cardiovascular disease in the general population.
Researchers at ETSU found that PEt-complexed CRP is able to capture low-density lipoprotein (LDL) cholesterol in human serum – often referred to as the “bad cholesterol” – which is linked to atherosclerosis.
Dr. Alok Agrawal, associate professor of pharmacology, says CRP in its original form does not bind to LDL, but when CRP is complexed with PEt, the binding to LDL will occur.
“CRP-bound LDL, through PEt, is totally inactive and is not engulfed by the macrophages present in the arterial wall. CRP-bound LDL did not transform human macrophages into LDL-loaded foam cells which contribute to the development of atherosclerosis. If macrophages don’t engulf LDL, then there will be no blockage in the arteries,” Agrawal said, adding that PEt-complexed CRP did not bind to high-density lipoprotein (HDL) cholesterol, the “good cholesterol” in the serum.
An earlier study had revealed that CRP would bind to LDL that had been oxidized or altered from its native, or original, state. Agrawal’s research team also found that PEt enhanced dramatically the binding of CRP to such modified forms of LDL.
Though the findings are still early, Agrawal suspects that the CRP-PEt complexes may prove effective in both reducing LDL cholesterol levels in the blood and in preventing formation of LDL-loaded macrophage foam cells in the arterial wall. Both are crucial in the process of atherosclerosis.
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