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


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.
Szabó
Csaba
C
Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary.
Zanchi
Anne
A
Komjáti
Katalin
K
Pacher
Pál
P
Krolewski
Andrzej S
AS
Quist
William C
WC
LoGerfo
Frank W
FW
Horton
Edward S
ES
Veves
Aristidis
A
D000109:Acetylcholine; D001706:Biopsy; D002467:Cell Nucleus / Q000201:enzymology / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000473:pathology; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D005542:Forearm; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000201:enzymology; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis / Q000096:biosynthesis; D012016:Reference Values; D018570:Risk Assessment; D012867:Skin / Q000098:blood supply; D013223:Statistics as Topic; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C002744:3-nitrotyrosine; D014443:Tyrosine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D011065:Poly(ADP-ribose) Polymerases; D000109:Acetylcholine