title: Energy restriction and exercise modulate angiopoietins and vascular endothelial growth factor expression in the cavernous tissue of high-fat diet-fed rats.
abstract: The purpose of the current study was to evaluate the effect of a high-fat (HF) diet, energy restriction and exercise on the expression of vascular endothelial growth factor (VEGF), angiopoietin (Ang) 1 and 2, and their receptors in rat corpus cavernosum (CC). Male Wistar rats were fed ad libitum with an HF diet for 8 or 16 weeks. After 8 weeks of the HF diet, a group of rats was subjected to energy restriction with or without exercise for 8 weeks. Control animals had free access to standard diet for the same period. After euthanasia, blood was collected and the penises removed for immunofluorescence assays (VEGF, VEGF receptor (VEGFR) 1 and 2, Ang1, Ang2 and Tie2) and semiquantification of VEGF, VEGFR1, VEGFR2, Ang1, Ang2, Tie2, endothelial nitric oxide synthase (eNOS) and Akt/phospho-Akt by Western blotting. HF diet-fed rats exhibited lower high-density lipoprotein cholesterol (HDL-c) levels, higher systolic blood pressure and an increased atherogenic index. A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs. The Akt pathway was activated by the HF diet. Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression. These results emphasize the role of diet on vascular function regulation, demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/Tie2 systems occurs before serum lipid changes and obesity onset, antedating structural atherosclerotic features.
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, Universidade do Porto-Alameda Prof, Hernâni Monteiro, Porto 4200-319, Portugal. inestomada@gmail.com
authors.forename: Inês
authors.initials: I
authors.lastname: Tomada
authors.forename: Nuno
authors.initials: N
authors.lastname: Tomada
authors.forename: Henrique
authors.initials: H
authors.lastname: Almeida
authors.forename: Delminda
authors.initials: D
authors.lastname: Neves
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D008076:Cholesterol, HDL / Q000097:blood; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage; D002149:Energy Intake; D008297:Male; D008868:Microtubule Proteins / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010413:Penis / Q000098:blood supply / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D008076:Cholesterol, HDL; D004041:Dietary Fats; D008868:Microtubule Proteins; D042461:Vascular Endothelial Growth Factor A; C044103:tektins; D052250:Nitric Oxide Synthase Type III; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt