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Placenta growth factor expression is regulated by stretch and correlates with microvascular dysfunction and plasma LDL
Author(s) -
Lloyd Pamela G.,
Mokelke Eric A.,
Kaser Shawn,
Alloosh Mouhamad,
Hou Yonghao,
Clauss Matthias,
Sturek Michael
Publication year - 2006
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.20.4.a716-d
Subject(s) - placental growth factor , arteriogenesis , medicine , hemodynamics , endocrinology , cardiology , artery , vascular resistance , vascular endothelial growth factor , angiogenesis , vegf receptors
Enlargement of preexisting collateral arteries (arteriogenesis) is regulated by hemodynamic forces (shear, stretch). We thus hypothesized that hemodynamic forces regulate placenta growth factor (PlGF, a VEGF‐related arteriogenic factor). We assessed PlGF expression in cultured human smooth muscle cells in response to 0–48 h. of cyclic stretch (N=6). Stretch mildly increased PlGF mRNA (~1.4 fold at 30 h). We further investigated hemodynamic regulation of PlGF expression in vivo by correlating coronary artery PlGF expression with microvascular function in Yucatan and Ossabaw swine. Microvascular function was assessed by administering bradykinin (BK, 4 ng/kg iv) and adenosine (ADO, 3 μg/kg iv) to anesthetized swine. Coronary vascular resistance (CVR) was calculated from measures of flow (Doppler Flowire) and vessel size (intravascular ultrasound). A higher CVR indicates microvascular dysfunction. A strong inverse correlation between PlGF levels and CVR was found in Ossabaws (N=8) for both BK (r 2 =0.51; p =0.02) and ADO (r 2 =0.30; p =0.05), with a similar but nonsignificant trend in Yucatans. PlGF mRNA was also inversely correlated with plasma total cholesterol (r 2 =0.28; p =0.01) and LDL (r 2 =0.27; p =0.01) in Yucatans and Ossabaws (N=22), but not HDL. These data suggest that LDL‐mediated microvascular dysfunction and altered sensing of hemodynamic forces might reduce PlGF expression and blunt arteriogenesis. Support: HL62552, RR13223, ADA (MS).