title: Telmisartan and N-acetylcysteine suppress group V secretory phospholipase A2 expression in TNFα-stimulated human endothelial cells and reduce associated atherogenicity.
abstract: 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 sPLA2-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.
authors: Department of Oral Health Management, School of Oral Health Sciences, Kyushu Dental College, Kitakyushu, Japan. sonoki@kyu-dent.ac.jp
authors: Kazuo
authors: K
authors: Sonoki
authors: Masanori
authors: M
authors: Iwase
authors: Shigehiro
authors: S
authors: Ohdo
authors: Ichiro
authors: I
authors: Ieiri
authors: Naoto
authors: N
authors: Matsuyama
authors: Yutaka
authors: Y
authors: Takata
authors: Takanari
authors: T
authors: Kitazono
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D050197:Atherosclerosis / Q000517:prevention & control; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D054505:Group V Phospholipases A2 / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D000077333:Telmisartan; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D001562:Benzimidazoles; D001565:Benzoates; D018932:Chemokine CCL2; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D054505:Group V Phospholipases A2; D000077333:Telmisartan; D000111:Acetylcysteine