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Abnormal Regulation of Placental Growth Factor in Skeletal Muscle of Western‐Diet Fed Mice
Author(s) -
Silva Asitha,
Lloyd Pamela
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1050.2
Subject(s) - medicine , endocrinology , skeletal muscle , apolipoprotein e , placental growth factor , femoral artery , vascular endothelial growth factor , disease , vegf receptors
Diabetics often develop peripheral artery disease (PAD). Arteriogenesis can preserve blood flow distal to occlusion and limit skeletal muscle ischemia in PAD, but is reduced in diabetics by an undefined mechanism. Placental growth factor (PLGF, a VEGF family protein) is a key arteriogenic factor. Therefore, we hypothesized that skeletal muscle PLGF expression and/or regulation could be abnormal in diabetic PAD. We tested this hypothesis in 3 mouse models with varying degrees of metabolic dysfunction: Western diet (WD) fed C57BL/6J (C57‐WD; n=52), control diet (CD) fed ApoE ‐/‐ (ApoE‐CD; n=38) and WD fed ApoE ‐/‐ (ApoE‐WD; n=32). CD fed C57BL/6J (C57‐CD; n=48) served as controls. Males and females were studied. Metabolic status was characterized by measuring relevant plasma values. After 6 mo on the diets, skeletal muscle PLGF was assessed under baseline conditions (n=58) and 3‐28 d post‐femoral artery occlusion (n=112). VEGF‐A was measured for comparison. Baseline skeletal muscle PLGF protein was decreased in all WD fed groups (p<0.005), with no effect of gender or strain. Regression analysis of PLGF vs metabolic parameters revealed modest correlation with plasma insulin (r 2 =0.44, p<0.0001). PLGF was sharply elevated in skeletal muscle of C57‐CD mice after femoral occlusion, peaking ~10 d post‐occlusion. This response was decreased and delayed in C57‐WD mice (p<0.05). Even more strikingly, upregulation of PLGF by occlusion was completely abolished in ApoE‐CD and ApoE‐WD mice. We conclude that in skeletal muscle, Western diet‐induced metabolic dysfunction both reduces baseline levels of PLGF and inhibits its upregulation by the physiological stimulus of occlusion. This phenomenon may contribute to the poor arteriogenic response in diabetes. Support: R01 HL084494 (PL).