The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes

Pal Pacher, Lucas Liaudet, Francisco Garcia Soriano, Jon G. Mabley, Éva Szabó, Csaba Szabo

Research output: Contribution to journalArticle

239 Citations (Scopus)

Abstract

Patients with diabetes exhibit a high incidence of diabetic cardiomyopathy and vascular complications, which underlie the development of retinopathy, nephropathy, and neuropathy and increase the risk of hypertension, stroke, and myocardial infarction. There is emerging evidence that the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) importantly contributes to the development of endothelial dysfunction in a streptozotocin-induced model of diabetes. We investigated the role of PARP activation in the pathogenesis of cardiac dysfunction in streptozotocin-induced and genetic (nonobese diabetic) models of diabetes in rats and mice. Development of diabetes was accompanied by hyperglycemia, cardiac PARP activation, a selective loss of endothelium-dependent vasodilation in the thoracic aorta, and an early diastolic dysfunction of the heart. Treatment with a novel potent phenanthridinonebased PARP inhibitor, PJ34, starting 1 week after the onset of diabetes, restored normal vascular responsiveness and significantly improved cardiac dysfunction, despite the persistence of severe hyperglycemia. The beneficial effect of PARP inhibition persisted even after several weeks of discontinuation of the treatment. Thus, PARP activation plays a central role in the pathogenesis of diabetic cardiovascular (cardiac as well as endothelial) dysfunction. PARP inhibitors may exert beneficial effects against the development of cardiovascular complications in diabetes.

Original languageEnglish (US)
Pages (from-to)514-521
Number of pages8
JournalDiabetes
Volume51
Issue number2
StatePublished - 2002
Externally publishedYes

Fingerprint

Poly(ADP-ribose) Polymerases
Streptozocin
Hyperglycemia
Diabetic Cardiomyopathies
Diabetic Angiopathies
Enzyme Activation
Diabetes Complications
Thoracic Aorta
Vasodilation
Endothelium
Blood Vessels
Stroke
Myocardial Infarction
Hypertension
Incidence
Therapeutics

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Pacher, P., Liaudet, L., Soriano, F. G., Mabley, J. G., Szabó, É., & Szabo, C. (2002). The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes. Diabetes, 51(2), 514-521.

The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes. / Pacher, Pal; Liaudet, Lucas; Soriano, Francisco Garcia; Mabley, Jon G.; Szabó, Éva; Szabo, Csaba.

In: Diabetes, Vol. 51, No. 2, 2002, p. 514-521.

Research output: Contribution to journalArticle

Pacher, P, Liaudet, L, Soriano, FG, Mabley, JG, Szabó, É & Szabo, C 2002, 'The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes', Diabetes, vol. 51, no. 2, pp. 514-521.
Pacher, Pal ; Liaudet, Lucas ; Soriano, Francisco Garcia ; Mabley, Jon G. ; Szabó, Éva ; Szabo, Csaba. / The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes. In: Diabetes. 2002 ; Vol. 51, No. 2. pp. 514-521.
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