Telmisartan and N-acetylcysteine suppress group v secretory phospholipase A₂ expression in TNFα-stimulated human endothelial cells and reduce associated atherogenicity

Group V secretory phospholipase A₂ (sPLA₂-V) hydrolyzes phosphatidylcholine in low-density lipoprotein (LDL) to increase lysophosphatidylcholine (LPC) content. Because in human umbilical vein endothelial cells (HUVEC), tumor necrosis factor alpha (TNFα)-induced sPLA₂-V expression, and LPC content in LDL and monocyte chemoattractant protein-1 mRNA were enhanced by incubation of LDL with TNFα-stimulated HUVEC, we investigated whether an angiotensin II receptor type 1 blocker, telmisartan, or an antioxidant drug, N-acetylcysteine (NAC), suppressed TNFα-induced sPLA₂-V expression. Telmisartan or NAC administered before and during TNFα stimulation diminished the increase of sPLA₂-V mRNA in HUVEC and reduced TNFα-induced sPLA ₂-V protein at 3 days after TNFα stimulation. Angiotensin II did not induce sPLA₂-V mRNA, and a peroxisome proliferator-activated receptor-γ antagonist, GW3335, did not influence the inhibitory effect of telmisartan on TNFα-induced sPLA₂-V mRNA. At 3 days after TNFα stimulation, 30 μM telmisartan or 20 mM NAC administered before and during TNFα stimulation prevented the enhancement of LPC content in LDL and monocyte chemoattractant protein-1 mRNA by LDL incubation with TNFα-stimulated HUVEC. A 2-month treatment with telmisartan in 29 hypertensive type 2 diabetic patients significantly reduced LPC content in circulating LDL. Telmisartan's suppressive effect on TNFα-induced sPLA₂-V expression may have beneficial effects in preventing proatherogenic changes of LDL.