Endothelial cell dysfunction in homocystinuria

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Abstract
This report describes the isolation and culture of venous endothelial cells from the umbilical cord of an obligate heterozygote for homocystinuria. The effect of different sulphur-containing amino acids on the viability and function of these cells was studied and compared with cultured normal endothelial cells. When endothelial cells were cultured in the presence of methionine (10 mmol/l) or homocystine (10 mmol/l), differences occurred between the viability and function of the heterozygote and normal cells in terms of 51Cr release and ability to prevent platelet adherence. The Cr release corrected for spontaneous release increases for the heterozygote cells after incubation for 21 h in the presence of methionine to 81.3% (control cells, range: 0–23.3%, n= 5) and in the presence of homocystine to 141% (control cells, range: 13.5–55.2%, n= 5). The total number of platelets that adhere to confluent monolayers increases for heterozygote cells cultured in the presence of methionine to 0.98 ± 107 platelets cm-2 (normal cells, range: 0.56–0.72 ± 107 platelets cm-2) and in the presence of homocystine to 1.41 ± 107 platelets cm-2 (normal cells, range: 0.94–1±06 ± 107 platelets cm-2). Both normal and control cells were sensitive to homocysteine. This study indicates for the first time what vascular endothelial cells, derived from an obligate heterozygote, are (partly) deficient in cysthathionine synthase and are more susceptible to methionine- and homocystine-mediated injury than normal endothelial cells. Consequently, in homocystinuria, due to dysfunction of the endothelial cells, toxic sulphur-containing amino acids may accumulate in these cells, causing injury of these cells.