Enhanced endothelium-dependent vasodilation in subjects with Proline7 substitution in the signal peptide of neuropeptide Y.
Neuropeptide Y (NPY) is a molecule that may have both vasoconstrictive and vasodilatory actions. A common polymorphism in the human NPY gene that results in the Leucine7 to Proline7 substitution (Leu7Pro) in the signal peptide part of the NPY was recently identified. This substitution has been associated with elevated serum cholesterol levels and with slightly accelerated progression rate of carotid intima-media thickness, thus suggesting increased risk of atherosclerosis in carriers of Pro7 substitution. Recent data also indicate that subjects with Pro7 substitution may have increased endothelial release of NPY. This study was undertaken to elucidate the effects of Leu7Pro polymorphism on arterial endothelial function. We measured flow-mediated endothelial-dependent dilatation (FMD) of the brachial artery in two separate populations: in 152 middle-aged men and in 95 prepubertal children. In both study populations, subjects with Pro7 substitution had 48-52% higher FMD compared with subjects having the wildtype (Leu7/Leu7) signal peptide sequence. We conclude that Pro7 substitution in signal peptide of the NPY is associated with enhanced endothelial-dependent vasodilation. Prospective studies are needed to determine whether Pro7 substitution is associated with increased or decreased risk of cardiovascular morbidity and mortality.
Järvisalo
Mikko J
MJ
Department of Clinical Physiology, University of Turku, Turku, Finland.
Jartti
Laura
L
Karvonen
Matti K
MK
Pesonen
Ullamari
U
Koulu
Markku
M
Marniemi
Jukka
J
Hammar
Niklas
N
Kaprio
Jaakko
J
Paakkunainen
Ulla
U
Simell
Olli
O
Raitakari
Olli T
OT
Rönnemaa
Tapani
T
D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D001795:Blood Pressure Determination; D001916:Brachial Artery; D002648:Child; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology / Q000235:genetics; D007930:Leucine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000235:genetics*; D011110:Polymorphism, Genetic; D011336:Probability; D011392:Proline / Q000235:genetics*; D011446:Prospective Studies; D021382:Protein Sorting Signals; D012016:Reference Values; D012307:Risk Factors; D012494:Sampling Studies; D018709:Statistics, Nonparametric; D014664:Vasodilation / Q000235:genetics* / Q000502:physiology
D009478:Neuropeptide Y; D021382:Protein Sorting Signals; D011392:Proline; D007930:Leucine