Effect of endothelium on beta-VLDL metabolism by cultured smooth muscle cells of differing phenotype.

The effect of endothelial cells (EC) on the binding and internalisation of beta-very low density lipoprotein (beta-VLDL) and the subsequent accumulation of lipid was investigated in cultured smooth muscle cells (SMC) of different phenotype. The following combinations were examined: (i) SMC cultured and incubated with 125I-beta-VLDL without EC: "control" cultures; (ii) SMC co-cultured with EC and incubated with 125I-beta-VLDL without EC: "separated" cultures; and (iii) SMC co-cultured with EC and incubated with 125I-beta-VLDL in the presence of EC: "co-incubated" cultures. SMC were in the contractile (CON), reversible synthetic (RS) or irreversible synthetic (IRS) phenotype and EC were either actively proliferating or confluent and quiescent. All three SMC phenotypes showed the greatest capacity to bind and internalise 125I-beta-VLDL with accumulation of lipid when "co-incubated" with confluent EC. SMC "co-incubated" with proliferating EC showed a lower capacity to bind and internalise the lipoprotein and accumulate lipid, while "control" SMC showed the lowest capacity for all phenotypes. IRS SMC bound more 125I-beta-VLDL than either RS or CON state phenotypes. In addition, IRS SMC "co-incubated" with confluent EC showed the greatest degree of binding, and IRS SMC incubated with EC-conditioned medium and EC-conditioned 125I-beta-VLDL showed a significant increase in binding above control (fresh medium and fresh 125I-beta-VLDL). The degree of binding 125I-beta-VLDL to SMC was affected by the functional state of the EC. That is, SMC "co-incubated" with confluent EC bound more lipoprotein than SMC "co-incubated" with the same number of proliferating EC. These results are consistent with observations by others who report preferential lipid accumulation in regions of denuded artery recently recovered by endothelium compared with regions lacking an endothelium. The results also indicate that the EC both modify the beta-VLDL particle and affect the biology of the SMC themselves.