Preconditioning of Human Smooth Muscle Cells via Cyclopentenone Prostaglandins Protects against Toxic Effects of Oxidized Low-Density Lipoprotein

Abstract

Human vascular smooth muscle cells (SMC) exhibit upregulation of inducible heat shock protein 70 (Hsp70), upon exposure to oxidized low-density lipoproteins (LDLox). 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 Δ12 prostaglandin J2 (Δ12PGJ2) before cells were exposed to LDLox. Hsp70 levels were measured after exposure to Δ12PGJ2 and before exposure to LDLox. Cell protection was monitored after LDLox exposure by determination of cell toxicity measured by cell lactate dehydrogenase (LDH) release into the medium. Cells treated with Δ12PGJ2 exhibited a 23-fold increase in Hsp70 levels and 56% lower LDH activity release after exposure to LDLox when compared to cells that were not pretreated with Δ12PGJ2. In addition, cells pretreated with prostaglandins that did not induce Hsp70 did not exhibit increased tolerance against the toxic effects of LDLox. The results support a protective role for Hsp70 against the toxic effects of LDLox and hint at the potential for the use of small molecules for the prevention of deleterious effects of LDLox through heat shock protein upregulation.