Preconditioning of human smooth muscle cells via cyclopentenone prostaglandins protects against toxic effects of oxidized low-density lipoprotein.
Human vascular smooth muscle cells (SMC) exhibit upregulation of inducible heat shock protein 70 (Hsp70), upon exposure to oxidized low-density lipoproteins (LDL(ox)). The presence of Hsp70 is thought to protect the cell against the toxic effects of the modified lipoprotein. In order to test this hypothesis, Hsp70 in SMC was upregulated by exposure to Delta(12) prostaglandin J(2) (Delta(12)PGJ(2)) before cells were exposed to LDL(ox). Hsp70 levels were measured after exposure to Delta(12)PGJ(2) and before exposure to LDL(ox). Cell protection was monitored after LDL(ox) exposure by determination of cell toxicity measured by cell lactate dehydrogenase (LDH) release into the medium. Cells treated with Delta(12)PGJ(2) exhibited a 23-fold increase in Hsp70 levels and 56% lower LDH activity release after exposure to LDL(ox) when compared to cells that were not pretreated with Delta(12)PGJ(2). In addition, cells pretreated with prostaglandins that did not induce Hsp70 did not exhibit increased tolerance against the toxic effects of LDL(ox). The results support a protective role for Hsp70 against the toxic effects of LDL(ox) and hint at the potential for the use of small molecules for the prevention of deleterious effects of LDL(ox) through heat shock protein upregulation.
Hamel
L
L
Cardiovascular Biology, Aventis, 500 Arcola Road, Collegeville, Pennsylvania 19426, USA.
Kenney
M
M
Clark
K
K
Merkel
L
L
Rojas
C
C
D003517:Cyclopentanes / Q000737:chemistry*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D019194:Ischemic Preconditioning; D008077:Lipoproteins, LDL / Q000633:toxicity*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011453:Prostaglandins / Q000737:chemistry / Q000502:physiology*
D003517:Cyclopentanes; D018840:HSP70 Heat-Shock Proteins; D008077:Lipoproteins, LDL; D011453:Prostaglandins; C099252:oxidized low density lipoprotein