Human endothelial cells exposed to oxidized LDL express hsp70 only when proliferating.
Oxidized LDL (OxLDL), a causal factor in atherosclerosis, is cytotoxic and triggers the expression of various heat shock proteins (hsps), among which is hsp70, in cultured animal and human cells. hsps constitutively act as molecular chaperones and in situations of stress protect other cellular proteins from potential denaturation caused by cytotoxic stimuli. The sensitivity of endothelial cells to OxLDL toxicity and accordingly the level of hsp70 expression depend on cell density. While confluent cells were relatively resistant to OxLDL toxicity and were not induced to express hsp70 when challenged with the lipoprotein (up to 800 micrograms/mL), sparse cells exhibited a concentration- and time-dependent expression of inducible hsp70, which increased up to fivefold to sixfold in unchallenged cells. Neither the activity of receptors recognizing OxLDL nor potentially protective cell products affected the stress response. Rather, we demonstrated that cell proliferation, which is high for sparse cultures and wound-healing monolayers, is responsible for these observations. We also demonstrated that the lipid moiety of OxLDL essentially accounts for the hsp-inducing effect of the lipoprotein. OxLDL has been detected in atherosclerotic lesions, which also show an increase of immunoreactive hsp72/73. We speculate that, in vivo, rapidly growing cells, such as those of lesion-prone areas, are more sensitive to the toxicity of OxLDL than are quiescent cells and that an increased expression of hsp70 may allow proliferating cells an increased chance of survival.
Zhu
W
W
Institute of Pharmacological Sciences, University of Milano, Italy.
Roma
P
P
Pirillo
A
A
Pellegatta
F
F
Catapano
A L
AL
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*
D018840:HSP70 Heat-Shock Proteins; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein