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Air Quality Criteria for Lead Volume II of II - (NEPIS)(EPA) - US ...

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AX5-74<br />

Reference<br />

Fugiwara<br />

et al. (1995)<br />

Carsia et al.<br />

(1995)<br />

Yamamoto<br />

et al. (1997)<br />

Species/<br />

Tissue<br />

Bovine aorta<br />

vascular<br />

smooth<br />

muscle cell<br />

Rat aorta<br />

VSMC cells<br />

(80–90%<br />

confluent)<br />

Human aorta<br />

VSMC and<br />

fetal lung<br />

fibroblasts<br />

(confluent)<br />

Table AX5-5.7. Studies <strong>of</strong> the Effect <strong>of</strong> <strong>Lead</strong> on Cultured Vascular Smooth Muscle Cells<br />

Pb Exposure Measured Parameters<br />

Age/<br />

Weight n Dosage Duration Pb Level CVS Other Reference Species/Tissue<br />

4 sets per<br />

experiment<br />

$3 sets per<br />

experiment<br />

5 sets per<br />

experiment<br />

Pb nitrate<br />

0.5–10 µM<br />

Pb citrate 100<br />

and 500 µg/L<br />

Pb chloride<br />

0.5–10 µM<br />

24 hrs — DNA synthesis Coincubation<br />

w/βFGF,<br />

αFGF. pDGF<br />

Time to<br />

confluence<br />

(~90% <strong>for</strong><br />

control<br />

experiments)<br />

Cell density (cell<br />

#/Cm 2 ), cell<br />

morphology,<br />

membrane lipid<br />

analysis, receptor<br />

densities (Ang-<strong>II</strong>,<br />

α, β, ANP<br />

24 hrs t-PA and PAI-1<br />

release<br />

Pb caused a<br />

concentration-dependent<br />

increase in DNA<br />

synthesis. Co-incubation<br />

w/βFGF and Pb resulted<br />

in an additive stimulation<br />

<strong>of</strong> VSMC DNA synth.<br />

However, Pb inhibited<br />

PDGF and αFGFinduced<br />

DNA synthesis.<br />

At low concentration, Pb<br />

caused VSMC<br />

hyperplasia, phenotypic<br />

trans<strong>for</strong>mation from<br />

spindle-to-cobblestone<br />

(neointima-like) shape,<br />

reduced Ang <strong>II</strong> receptor<br />

density without changing<br />

α, β, ANP receptors,<br />

increased arachidonic<br />

acid content <strong>of</strong> cell<br />

membrane.<br />

At 2 µM or higher<br />

concentrations, Pb<br />

resulted in a<br />

concentration-dependent<br />

decline in t-PA release in<br />

both cell types. Pb<br />

increased PAI-1 release<br />

in fibroblasts but lowered<br />

PAI-1 in VSMC.

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