Poly(ADP-ribose) polymerase is activated in subjects at risk of developing type 2 diabetes and is associated with impaired vascular reactivity

被引:141
作者
Szabó, C
Zanchi, A
Komjáti, K
Pacher, P
Krolewski, AS
Quist, WC
LoGerfo, FW
Horton, ES
Veves, A
机构
[1] Beth Israel Deaconess Med Ctr, Microcirculat Lab, Joslin Diabet Ctr, Boston, MA 02215 USA
[2] Beth Israel Deaconess Med Ctr, Div Vasc Surg, Joslin Diabet Ctr, Boston, MA 02215 USA
[3] Harvard Univ, Sch Med, Boston, MA 02138 USA
[4] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary
[5] Inotek Pharmaceut Corp, Beverly, MA USA
关键词
diabetes mellitus; endothelium; acetylcholine; microcirculation;
D O I
10.1161/01.CIR.0000038365.78031.9C
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-We have previously shown that endothelial function is impaired not only in diabetes but also in subjects at risk of developing type 2 diabetes. We hypothesized that changes in the expression or activity of the endothelial isoform of nitric oxide synthase (eNOS), the receptor for advanced glycation end products (RAGE), and poly(ADP-ribose) polymerase (PARP) are related to this impairment. Methods and Results-We included a control group of 21 healthy subjects, a group of 22 healthy individuals with parental history of type 2 diabetes, a group of 23 subjects with impaired glucose tolerance, and a group of 21 type 2 diabetic patients. Two 2-mm forearm skin biopsies were taken from each participant and used for measurements. The percentage of PARP-positive endothelial nuclei was higher in the group with parental history of type 2 diabetes and diabetic patients compared with the controls (P<0.001). Immunoreactivity for nitrotyrosine (a marker of reactive nitrogen species) was higher in the diabetic group compared with all other groups (P<0.01). No differences in the expression of eNOS and RAGE were found among all 4 groups. The polymorphism of the eNOS gene was also studied and was not found to influence eNOS expression or microvascular functional measurements. Conclusions-PARP activation is present in healthy subjects at risk of developing diabetes as well as in established type 2 diabetic patients, and it is associated with impairments in the vascular reactivity in the skin microcirculation.
引用
收藏
页码:2680 / 2686
页数:7
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