TY - JOUR
T1 - Effects of human endothelial gene polymorphisms on cellular responses to hyperglycaemia: Role of NOS3 (Glu298Asp) and ACE (I/D) polymorphisms
AU - Joshi, Mandar
AU - Wattanapitayakul, Sunvara
AU - Schanbacher, Brandon
AU - Bauer, John
PY - 2011
Y1 - 2011
N2 - The functional relevance of NOS3 and ACE genetic variations to endothelial cell function is largely unstudied. Here we tested the functional relevance of the NOS3 (Glu298Asp) polymorphism and ACE (I/D) polymorphism in endothelial cells in vitro. Our hypothesis was that these genetic polymorphisms alter endothelial cell sensitivity to glucose and 3-nitrotyrosine (3NT). Genotyped HUVECs were incubated with glucose, free 3NT or a combination of these two toxicants. Significant differences in glucose-induced cell death and free 3NT-induced cell death were observed among the NOS3 genotypes. Combined glucose/3NT caused increased toxicity among the NOS3 genotypes. No differences were observed among the ACE genotypes in their responses to glucose/3NT. These data demonstrate that the NOS3 genotype may be an important predictor of, or be mechanistically involved in, endothelial vulnerability, whereas the ACE I/D genotype is apparently less important. Thus this NOS3 genetic variation may play a role in vulnerability to endothelium-dependent diabetic vascular complications.
AB - The functional relevance of NOS3 and ACE genetic variations to endothelial cell function is largely unstudied. Here we tested the functional relevance of the NOS3 (Glu298Asp) polymorphism and ACE (I/D) polymorphism in endothelial cells in vitro. Our hypothesis was that these genetic polymorphisms alter endothelial cell sensitivity to glucose and 3-nitrotyrosine (3NT). Genotyped HUVECs were incubated with glucose, free 3NT or a combination of these two toxicants. Significant differences in glucose-induced cell death and free 3NT-induced cell death were observed among the NOS3 genotypes. Combined glucose/3NT caused increased toxicity among the NOS3 genotypes. No differences were observed among the ACE genotypes in their responses to glucose/3NT. These data demonstrate that the NOS3 genotype may be an important predictor of, or be mechanistically involved in, endothelial vulnerability, whereas the ACE I/D genotype is apparently less important. Thus this NOS3 genetic variation may play a role in vulnerability to endothelium-dependent diabetic vascular complications.
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21844127
U2 - 10.1177/1479164111416679
DO - 10.1177/1479164111416679
M3 - Article
SN - 1479-1641
VL - 8
SP - 276
EP - 283
JO - Diabetes & Vascular Disease Research
JF - Diabetes & Vascular Disease Research
IS - 4
ER -