title: Inhibition of poly-ADP ribose polymerase enzyme activity prevents hyperglycemia-induced impairment of angiogenesis during wound healing.
abstract: We previously reported a zebrafish model of type I diabetes mellitus (DM) that can be used to study the hyperglycemic (HG) and metabolic memory (MM) states within the same fish. Clinically, MM is defined as the persistence of diabetic complications even after glycemic control is pharmacologically achieved. In our zebrafish model, MM occurs following β-cell regeneration, which returns fish to euglycemia. During HG, fish acquire tissue deficits reflective of the complications seen in patients with DM and these deficits persist after fish return to euglycemia (MM). The unifying mechanism for the induction of diabetic complications involves a cascade of events that is initiated by the HG stimulation of poly-ADP ribose polymerase enzyme (Parp) activity. Additionally, recent evidence shows that the HG induction of Parp activity stimulates changes in epigenetic mechanisms that correlate with the MM state and the persistence of complications. Here we report that wound-induced angiogenesis is impaired in DM and remains impaired when fish return to a euglycemic state. Additionally, inhibition of Parp activity prevented the HG-induced wound angiogenesis deficiency observed. This approach can identify molecular targets that will provide potential new avenues for therapeutic discovery as angiogenesis imbalances are associated with all HG-damaged tissues.
authors: Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois.
authors: Michael P
authors: MP
authors: Sarras
authors: Samantha
authors: S
authors: Mason
authors: Geoffrey
authors: G
authors: McAllister
authors: Robert V
authors: RV
authors: Intine
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003922:Diabetes Mellitus, Type 1; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000150:complications*; D007546:Isoquinolines / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014945:Wound Healing / Q000187:drug effects*; D015027:Zebrafish
chemical_list: D001786:Blood Glucose; D007546:Isoquinolines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C095653:1,5-dihydroxyisoquinoline