PMID- 31397166 OWN - NLM STAT- MEDLINE DCOM- 20200406 LR - 20201001 IS - 1522-1539 (Electronic) IS - 0363-6135 (Print) IS - 0363-6135 (Linking) VI - 317 IP - 4 DP - 2019 Oct 1 TI - Placental growth factor levels in quadriceps muscle are reduced by a Western diet in association with advanced glycation end products. PG - H851-H866 LID - 10.1152/ajpheart.00511.2018 [doi] AB - In peripheral artery disease (PAD), atherosclerotic occlusion chronically impairs limb blood flow. Arteriogenesis (collateral artery remodeling) is a vital adaptive response to PAD that protects tissue from ischemia. People with type II diabetes have a high risk of developing PAD and would benefit from arteriogenesis. However, arteriogenesis is suppressed in people with diabetes by a multifaceted mechanism which remains incompletely defined. Upregulation of placental growth factor (PLGF) is a key early step in arteriogenesis. Therefore, we hypothesized that metabolic dysfunction would impair PLGF expression in skeletal muscle. We tested this hypothesis in C57BL/6J and ApoE(-/-) mice of both sexes fed a Western diet (WD) for 24 wk. We first assessed baseline levels of PLGF, vascular endothelial growth factor (VEGF-A), and VEGF receptor 1 (VEGFR1) protein in hindlimb skeletal muscle. Only PLGF was consistently decreased by the WD. We next investigated the effect of 24 wk of the WD on the response of PLGF, VEGF-A, VEGFR1, and monocyte chemoattractant protein-1 (MCP-1) to the physiological stimulus of vascular occlusion. Hindlimb ischemia was induced in mice by gradual femoral artery occlusion using an ameroid constrictor. Growth factor levels were measured 3-28 days postsurgery. In C57BL/6J mice, the WD decreased and delayed upregulation of PLGF and abolished upregulation of VEGF-A and VEGFR1 but had no effect on MCP-1. In ApoE(-/-) mice fed either diet, all factors tested failed to respond to occlusion. Metabolic phenotyping of mice and in vitro studies suggest that an advanced glycation end product/TNFalpha-mediated mechanism could contribute to the effects observed in vivo.NEW & NOTEWORTHY In this study, we tested the effect of a Western diet on expression of the arteriogenic growth factor placental growth factor (PLGF) in mouse skeletal muscle. We provide the first demonstration that a Western diet interferes with both baseline expression and hindlimb ischemia-induced upregulation of PLGF. We further identify a potential role for advanced glycation end product/TNFalpha signaling as a negative regulator of PLGF. These studies provide insight into one possible mechanism by which type II diabetes may limit collateral growth. FAU - Silva, Asitha T AU - Silva AT AD - Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma. FAU - Rouf, Farzana AU - Rouf F AD - Department of Mechanical and Aerospace Engineering, Oklahoma State University, Stillwater, Oklahoma. FAU - Semola, Oluwayemisi A AU - Semola OA AD - Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma. FAU - Payton, Mark E AU - Payton ME AD - Department of Statistics, Oklahoma State University, Stillwater, Oklahoma. FAU - Lovern, Pamela C AU - Lovern PC AUID- ORCID: 0000-0001-7943-4722 AD - Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma. LA - eng GR - R01 HL084494/HL/NHLBI NIH HHS/United States GR - R56 HL084494/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20190809 PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Glycation End Products, Advanced) RN - 0 (Pgf protein, mouse) RN - 0 (Tnf protein, mouse) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (vascular endothelial growth factor A, mouse) RN - 144589-93-5 (Placenta Growth Factor) RN - EC 2.7.10.1 (Flt1 protein, mouse) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1) SB - IM MH - Animals MH - Chemokine CCL2/metabolism MH - Collateral Circulation MH - *Diet, Western MH - Disease Models, Animal MH - Down-Regulation MH - Female MH - Glycation End Products, Advanced/*metabolism MH - Hindlimb MH - Ischemia/genetics/*metabolism MH - Male MH - Mice, Inbred C57BL MH - Mice, Knockout, ApoE MH - *Neovascularization, Physiologic MH - Placenta Growth Factor/*metabolism MH - Quadriceps Muscle/*blood supply/*metabolism/physiopathology MH - Regional Blood Flow MH - Signal Transduction MH - Tumor Necrosis Factor-alpha/metabolism MH - Vascular Endothelial Growth Factor A/metabolism MH - Vascular Endothelial Growth Factor Receptor-1/metabolism PMC - PMC6843019 OTO - NOTNLM OT - TNFalpha OT - advanced glycation end products OT - arteriogenesis OT - collateral arteries OT - hindlimb ischemia OT - peripheral artery disease OT - type II diabetes COIS- No conflicts of interest, financial or otherwise, are declared by the authors. EDAT- 2019/08/10 06:00 MHDA- 2020/04/09 06:00 PMCR- 2020/10/01 CRDT- 2019/08/10 06:00 PHST- 2019/08/10 06:00 [pubmed] PHST- 2020/04/09 06:00 [medline] PHST- 2019/08/10 06:00 [entrez] PHST- 2020/10/01 00:00 [pmc-release] AID - H-00511-2018 [pii] AID - 10.1152/ajpheart.00511.2018 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2019 Oct 1;317(4):H851-H866. doi: 10.1152/ajpheart.00511.2018. Epub 2019 Aug 9.