Department of Oral Health Management, School of Oral Health Sciences, Kyushu Dental College, Kitakyushu, Japan.
J Cardiovasc Pharmacol. 2012 Oct;60(4):367-74. doi: 10.1097/FJC.0b013e3182646ccc.
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.
组 V 分泌型磷脂酶 A2（sPLA2-V）水解低密度脂蛋白（LDL）中的磷脂酰胆碱，增加溶血磷脂酰胆碱（LPC）的含量。在人脐静脉内皮细胞（HUVEC）中，肿瘤坏死因子-α（TNFα）诱导 sPLA2-V 的表达，以及 LDL 中的 LPC 含量和单核细胞趋化蛋白-1 mRNA 的含量，都因 LDL 与 TNFα 刺激的 HUVEC 孵育而增加，因此我们研究了血管紧张素 II 受体 1 阻滞剂替米沙坦或抗氧化剂 N-乙酰半胱氨酸（NAC）是否抑制 TNFα 诱导的 sPLA2-V 表达。替米沙坦或 NAC 在 TNFα 刺激前和刺激期间给予可减少 HUVEC 中 sPLA2-V mRNA 的增加，并在 TNFα 刺激 3 天后减少 TNFα 诱导的 sPLA2-V 蛋白。血管紧张素 II 不会诱导 sPLA2-V mRNA，过氧化物酶体增殖物激活受体-γ 拮抗剂 GW3335 也不会影响替米沙坦对 TNFα 诱导的 sPLA2-V mRNA 的抑制作用。在 TNFα 刺激 3 天后，在 TNFα 刺激前和刺激期间给予 30 μM 替米沙坦或 20 mM NAC 可防止 LDL 孵育与 TNFα 刺激的 HUVEC 孵育后 LDL 中 LPC 含量和单核细胞趋化蛋白-1 mRNA 的增强。29 例高血压 2 型糖尿病患者接受替米沙坦 2 个月治疗可显著降低循环 LDL 中的 LPC 含量。替米沙坦对 TNFα 诱导的 sPLA2-V 表达的抑制作用可能对预防 LDL 的促动脉粥样硬化变化具有有益作用。
