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

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AX5-72<br />

Reference<br />

Fujiwara and<br />

Kaji<br />

(1999)<br />

Kaji et al.<br />

(1991)<br />

Kaji et al.<br />

(1997)<br />

Table AX5-5.6 (cont’d). Effects <strong>of</strong> <strong>Lead</strong> on Cultured Endothelial Cell Proliferation, Angiogenesis, and<br />

Production <strong>of</strong> Heparan Sulfate Proteoglycans and tPA<br />

Species/<br />

Tissue<br />

Bovine aorta<br />

endothelial<br />

cells<br />

Bovine aorta<br />

endothelial<br />

cells<br />

Bovine aorta<br />

endothelial<br />

cells<br />

(confluent)<br />

Pb Exposure Measured Parameters<br />

Age/<br />

Weight n Dosage Duration Pb Level CVS Other Interventions Results<br />

— 4 sets per<br />

experiment<br />

— 4–5 sets per<br />

experiment<br />

Pb nitrate<br />

0.5, 1, 2 µM<br />

Pb nitrate<br />

0, 1–20 µM<br />

— N/A Pb chloride<br />

10 M<br />

12–48 hrs βFGF production/<br />

distribution<br />

Heparan sulfate<br />

production (sulfate<br />

incorporation)<br />

DNA synthesis (cell<br />

proliferation)<br />

βFGF binding assay<br />

24–48 hrs Glycosaminoglycan<br />

(GAG) synthesis<br />

(sulfate incorporation)<br />

24 hrs N/A Synthesis <strong>of</strong> heparan<br />

sulfate proteoglycans<br />

(HSPGs) and their core<br />

proteins<br />

Heparin, AntiβFGF<br />

antibody<br />

Pb and anti-βFGF alone<br />

or together equally<br />

reduced DNA synthesis.<br />

PB did not change<br />

endogenous βFGF<br />

production but reduced<br />

its HSPG-bound<br />

component. This was<br />

due to diminished<br />

heparan sulfate synthesis<br />

as opposed to<br />

interference with βFGF<br />

binding property.<br />

At 10 FM, Pb<br />

significantly reduced<br />

production <strong>of</strong> total<br />

GAGs. Heparan sulfate<br />

was reduced more<br />

severely than other<br />

GAGs. Cell surface<br />

GAG was reduced more<br />

severely than found in<br />

the medium.<br />

In confluent cells, Pb<br />

suppressed incorporation<br />

<strong>of</strong> precursors into HSPG<br />

in the cell layer to a<br />

greater extent than<br />

chondroitin/dermatan<br />

sulfate proteoglycans. Pb<br />

suppressed lowmolecular<br />

weight HSPGs<br />

more than the highmolecular<br />

weight<br />

subclass. The core<br />

proteins were slightly<br />

increased by Pb<br />

exposure.

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