The effect of endogenous preproneuropeptide Y leucine 7 to proline 7 polymorphism on growth and apoptosis in primary cultured HUVECs.
Neuropeptide Y (NPY) is a universally expressed neuropeptide involved in the regulation of several physiological functions. The rather common leucine7 to proline7 (L7P) polymorphism in the signal peptide of preproNPY is a functional substitution, which changes the processing and release of NPY in cells. The mutation is associated with altered lipid levels and accelerated atherosclerosis in humans. Based on previous studies, we investigated the effect of the Pro7 allele in endothelial cells, which are known to play a role in the development of atherosclerosis. Cell proliferation and apoptosis were studied in primary cultured, genotyped human umbilical vein endothelial cells (HUVECs). Our results indicate that cells with the [p.L7]+[p.P7] genotype seem to have a tendency to be more sensitive to the growth stimulating effect of NPY and less sensitive to the effect of vascular endothelial growth factor compared to cells with the [p.L7]+[p.L7] genotype. Additionally, cells with the [p.L7]+[p.P7] genotype seem to be more sensitive to apoptosis than [p.L7]+[p.L7] cells. We speculate that the L7P substitution in preproNPY might cause a state of cellular pre-senescence, leading to endothelial dysfunction. This might be one reason for the associations of the L7P polymorphism with atherosclerosis and type II diabetes found in clinical studies.
Kaipio
Katja
K
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
Kallio
Jaana
J
Pesonen
Ullamari
U
D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018613:Microscopy, Confocal; D009478:Neuropeptide Y / Q000235:genetics / Q000502:physiology*; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology*
D009478:Neuropeptide Y