Hsp70 expression in monocytes from patients with peripheral arterial disease and healthy controls: monocyte Hsp70 in PAD.
BACKGROUND
Heat shock proteins (HSP) are induced during cellular stress. Their role is to chaperone cellular proteins giving protection from denaturation and ultimately preventing cell death. Monocytes are key cells involved in atherosclerosis and are highly responsive to HSP induction. Therefore, we wished to examine monocyte Hsp70 expression and induction in patients with peripheral arterial disease (PAD) and in healthy controls.


METHODS
We measured cellular Hsp70 levels in freshly isolated monocytes and released Hsp70 levels in plasma and monocyte culture supernatants, obtained from patients with PAD and from healthy controls. We assessed the effect of statin therapy on Hsp70 levels and examined monocyte cell survival in culture with and without immunological stress.


RESULTS
Monocyte cellular Hsp70 was lower in patients with PAD compared to healthy controls (11.3 +/- 7.4 ng/10(6) cells vs 20.7 +/- 16.0 ng/10(6) cells; p < 0.001). Individuals on statin therapy from both PAD and control groups had lower monocyte Hsp70 compared to those not treated with statins. Concentrations of Hsp70 released into culture supernatants were not dependent on PAD or statin therapy. Cell survival was inversely associated with Hsp70 concentrations in culture supernatants but had no association with cellular concentrations of Hsp70.


CONCLUSIONS
Cellular Hsp70 and released Hsp70 may play different roles in monocyte health. Whilst induced Hsp70 destined for release appears to be unaffected in PAD, mechanisms responsible for cellular retention of Hsp70 may provide an area for future therapeutic targets in vascular disease.
Madden
Jacqueline
J
Institute of Human Nutrition, School of Medicine, University of Southampton, IDS Building, MP887 Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. jm24@soton.ac.uk
Coward
Jenifer C
JC
Shearman
Cliff P
CP
Grimble
Robert F
RF
Calder
Philip C
PC
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018840:HSP70 Heat-Shock Proteins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D015999:Multivariate Analysis; D016491:Peripheral Vascular Diseases / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors