Key result
Modifying LDL with gangliosides reduces cultured smooth muscle cell uptake ~80%.
Why the study?
The uptake of low-density lipoproteins by cultured human arterial smooth muscle cells is controlled by the sialic acid content of LDL particles.
Does the sialic acid content of low-density lipoproteins control their binding and uptake by cultured human cells?
Does the sialic acid content of low-density lipoproteins control their binding and uptake by cultured human cells?
The sialic acid content of low-density lipoproteins is a key regulator of their high-affinity receptor-mediated uptake by human arterial smooth muscle cells and fibroblasts.
Answers are grounded in this paper and cite their sources.
Sialic acid modification may alter LDL uptake in vitro; leaves open its relevance to human atherosclerosis and requires in vivo confirmation.
The (high-affinity receptor)-mediated uptake of homologous low-density (low-rho) lipoproteins by cultured human arterial smooth muscle cells or human skin fibroblasts is controlled by the sialic acid content of low-rho lipoprotein particles. This conclusion is derived from the following results. 1. Gangliosides incubated with native low-rho lipoproteins associate with low-rho lipoprotein particles. Low-rho lipoproteins modified by associated GLac1, GGtet1, and GGtet2b + GGtet3 gangliosides are internalized by arterial smooth muscle cells at a rate up to 80% lower than native low-rho lipoproteins or those preincubated with desialized gangliosides. 2. The inhibitory effect of gangliosides is specific for high affinity uptake and not detectable on skin fibroblasts deficient in low-rho-lipoprotein receptor. 3. Desialyzed low-rho lipoproteins are internalized by smooth muscle cells up to 100% faster than native low-rho lipoproteins, the enhancement of uptake corresponding to the degree of desialization.
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Filipović et al. (1979) studied this question. Sialic acid content modification of low-density lipoproteins vs. Native low-density lipoproteins was evaluated on Receptor-mediated uptake of low-density lipoproteins by cultured cells. Modifying the sialic acid content of low-density lipoproteins with gangliosides reduced their uptake by cultured smooth muscle cells by up to 80%, whereas desialization increased uptake by up to 100%.
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