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

Csaba Szabo, Anne Zanchi, Katalin Komjáti, Pál Pacher, Andrzej S. Krolewski, William C. Quist, Frank W. LoGerfo, Edward S. Horton, Aristidis Veves

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

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 (Pα0.001). 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.

Original languageEnglish (US)
Pages (from-to)2680-2686
Number of pages7
JournalCirculation
Volume106
Issue number21
DOIs
StatePublished - Nov 19 2002
Externally publishedYes

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Poly(ADP-ribose) Polymerases
Nitric Oxide Synthase Type III
Type 2 Diabetes Mellitus
Blood Vessels
Protein Isoforms
Healthy Volunteers
Reactive Nitrogen Species
Skin
Glucose Intolerance
Microcirculation
Forearm
Biopsy
Control Groups
Genes
Advanced Glycosylation End Product-Specific Receptor
Soluble Guanylyl Cyclase

Keywords

  • Acetylcholine
  • Diabetes mellitus
  • Endothelium
  • Microcirculation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Poly(ADP-ribose) polymerase is activated in subjects at risk of developing type 2 diabetes and is associated with impaired vascular reactivity. / Szabo, Csaba; Zanchi, Anne; Komjáti, Katalin; Pacher, Pál; Krolewski, Andrzej S.; Quist, William C.; LoGerfo, Frank W.; Horton, Edward S.; Veves, Aristidis.

In: Circulation, Vol. 106, No. 21, 19.11.2002, p. 2680-2686.

Research output: Contribution to journalArticle

Szabo, C, Zanchi, A, Komjáti, K, Pacher, P, Krolewski, AS, Quist, WC, LoGerfo, FW, Horton, ES & Veves, A 2002, 'Poly(ADP-ribose) polymerase is activated in subjects at risk of developing type 2 diabetes and is associated with impaired vascular reactivity', Circulation, vol. 106, no. 21, pp. 2680-2686. https://doi.org/10.1161/01.CIR.0000038365.78031.9C
Szabo, Csaba ; Zanchi, Anne ; Komjáti, Katalin ; Pacher, Pál ; Krolewski, Andrzej S. ; Quist, William C. ; LoGerfo, Frank W. ; Horton, Edward S. ; Veves, Aristidis. / Poly(ADP-ribose) polymerase is activated in subjects at risk of developing type 2 diabetes and is associated with impaired vascular reactivity. In: Circulation. 2002 ; Vol. 106, No. 21. pp. 2680-2686.
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AU - Szabo, Csaba

AU - Zanchi, Anne

AU - Komjáti, Katalin

AU - Pacher, Pál

AU - Krolewski, Andrzej S.

AU - Quist, William C.

AU - LoGerfo, Frank W.

AU - Horton, Edward S.

AU - Veves, Aristidis

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N2 - 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 (Pα0.001). 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.

AB - 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 (Pα0.001). 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.

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