Pioglitazone prevents capillary rarefaction in streptozotocin-diabetic rats independently of glucose control and vascular endothelial growth factor expression

Item Type:	Article
Title:	Pioglitazone prevents capillary rarefaction in streptozotocin-diabetic rats independently of glucose control and vascular endothelial growth factor expression
Creators Name:	Ashoff, A. and Qadri, F. and Eggers, R. and Joehren, O. and Raasch, W. and Dendorfer, A.
Abstract:	Background/Aims: Reduction of capillary network density occurs early in the development of metabolic syndrome and may be relevant for the precipitation of diabetes. Agonists of the peroxisome proliferator-activated receptor (PPAR)-gamma transcription factor are vasculoprotective, but their capacity for structural preservation of the microcirculation is unclear. Methods: Male Wistar rats were rendered diabetic by streptozotocin and treated with pioglitazone in chow for up to 12 weeks. Capillary density was determined in heart and skeletal muscle after platelet endothelial cell adhesion molecule-1 (PECAM-1) immunostaining. Hallmarks of apoptosis and angiogenesis were determined. Results: Capillary density deteriorated progressively in the presence of hyperglycemia (from 971/mm2 to 475/mm2 in quadriceps muscle during 13 weeks). Pioglitazone did not influence plasma glucose, left ventricular weight, or body weight but nearly doubled absolute and relative capillary densities compared to untreated controls (1.2 vs. 0.6 capillaries/myocyte in heart and 1.5 vs. 0.9 capillaries/myocyte in quadriceps muscle) after 13 weeks of diabetes. No antiapoptotic or angiogenic influence of pioglitazone was detected while a reduced expression of hypoxia-inducible factor-3α and PPAR coactivator-1α (PGC-1alpha) mRNA as well as vascular endothelial growth factor (VEGF) protein possibly occurred as a consequence of improved vascularization. Conclusion: Pioglitazone preserves microvascular structure in diabetes independently of improvements in glycemic control and by a mechanism unrelated to VEGF-mediated angiogenesis.
Keywords:	Diabetic Angiopathies, Capillaries, Rarefaction, Peroxisome Proliferator-Activated Receptor-gamma, Vascular Endothelial Growth Factor, Oxygen Radicals, Animals, Rats
Source:	Journal of Vascular Research
ISSN:	1018-1172
Publisher:	Karger
Volume:	49
Number:	3
Page Range:	260-266
Date:	May 2012
Official Publication:	https://doi.org/10.1159/000335214
PubMed:	View item in PubMed

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