Hypertension augments cardiac Toll-like receptor 4 expression and activity
Hypertension augments cardiac Toll-like receptor 4 expression and activity
复制标题
DOI：
10.1038/hr.2010.270
复制
发表时间：
2011-05-01
影响因子：
5.4
通讯作者：
Baumann, Marcus
中科院分区：
文献类型：
--
作者：
Eissler, Ruth;Schmaderer, Christoph;Baumann, Marcus
高血压导致以轻度炎症为特征的心脏肥大。Toll样受体（TLR）是先天免疫系统的成员，可导致心力衰竭。我们假设高血压伴随着TLR 4表达和活性的增强。在未经治疗的自发性高血压大鼠（SHR）和血压正常的Wistar-Kyoto大鼠（WKY; 4、8、16周）中测定心脏TLR 4表达。此外，用内源性TLR 4配体硫酸乙酰肝素（HS）刺激8周龄大鼠的心脏;评估促炎性mRNA模式（肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6、单核细胞趋化蛋白（MCP）-1）。此外，我们还用L-NAME（N（omega）-硝基-L-精氨酸甲酯盐酸盐）诱导WKY大鼠高血压。在两种高血压模型中，评估了雷米普利对TLR 4密度的影响。通过荧光激活细胞分选分析研究心脏TLR 4分布。SHR的血压和心脏重量/体重比（HW/BW）升高。与WKY相比，青春期和成年期组成型TLR 4表达增加，但年轻SHR没有。TLR 4染色在心肌细胞中明显。HS导致心脏组织中TNF-α和IL-6 mRNA反应加重，这在SHR中显著显著。雷米普利（10 mg kg（-1）/d）降低SHR的血压、HW/BW和TLR 4表达。L-NAME还增加WKY中TLR 4的表达。拉米替尼（每天1毫克/千克）降低血压，但TLR 4的表达不受影响。然而，高剂量雷米普利（10 mg/kg/天）降低了TLR 4的表达。从青春期开始，SHR表现出心脏TLR 4表达增强。TLR 4在L-NAME诱导的高血压中也上调。因此，增强的TLR 4表达可能与高血压的发展和维持有关。最后，血管紧张素转换酶抑制剂的抗高血压、抗炎作用在治疗剂量下对TLR 4表达没有影响，但在高剂量模型中。高血压研究（2011）34，551-558; doi：10.1038/hr.2010.270;在线发表2011年1月20日
Hypertension causes cardiac hypertrophy characterized by low-grade inflammation. Toll-like receptors (TLRs), members of the innate immune system, contribute to cardiac failure. We hypothesized that hypertension is accompanied by enhanced TLR4 expression and activity. Cardiac TLR4 expression was determined in untreated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY; 4, 8, 16 weeks). Besides, hearts of 8-week-old rats were stimulated with the endogenous TLR4 ligand heparansulfate (HS); the proinflammatory mRNA pattern was assessed (tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, monocyte chemotactic protein (MCP)-1). Additionally, we induced hypertension in WKY by L-NAME (N(omega)-nitro-L-arginine-methylester hydrochloride). In both hypertension models the effect of ramipril on TLR4 density was assessed. Cardiac TLR4 distribution was investigated by fluorescence-activated cell sorting analysis. Blood pressure (BP) and heart weight/body weight ratio (HW/BW) were elevated in SHR. Constitutive TLR4 expression was augmented in adolescent and adult, but not young SHR compared with WKY. TLR4 staining was pronounced in cardiomyocytes. HS entailed an aggravated TNF-alpha and IL-6 mRNA response in cardiac tissue, which was significantly pronounced in SHR. Ramipril (10 mg kg(-1) per day) reduced BP, HW/BW and TLR4 expression in SHR. L-NAME also augmented TLR4 expression in WKY. Ramipril (1 mg kg(-1) per day) lowered BP but TLR4 expression remained unaffected. High-dose ramipril (10 mg kg(-1) per day) however decreased TLR4 expression. Starting from adolescence SHR demonstrated enhanced cardiac TLR4 expression. TLR4 was also upregulated in L-NAME induced hypertension. Thus, enhanced TLR4 expression might be linked to the development and maintenance of hypertension. Finally, the antihypertensive, anti-inflammatory action of angiotensin-converting-enzyme inhibition had no effect on TLR4 expression in therapeutic doses but in a high-dose model. Hypertension Research (2011) 34, 551-558; doi:10.1038/hr.2010.270; published online 20 January 2011