Implication of Free Fatty Acids in Thrombin Generation and Fibrinolysis in Vascular Inflammation in Zucker Rats and Evolution with Aging.
Implication of Free Fatty Acids in Thrombin Generation and Fibrinolysis in Vascular Inflammation in Zucker Rats and Evolution with Aging.
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DOI：
10.3389/fphys.2017.00949
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发表时间：
2017
影响因子：
4
通讯作者：
Regnault V
中科院分区：
文献类型：
--
作者：
Lagrange J;Didelot M;Mohamadi A;Walton LA;Bloemen S;de Laat B;Louis H;Thornton SN;Derby B;Sherratt MJ;Fève B;Challande P;Akhtar R;Cruickshank JK;Lacolley P;Regnault V
背景资料：代谢综合征（MetS）和衰老与凝血因子的改变、血管炎症和血栓形成风险增加有关。目的：我们的目的是确定伴随的变化，凝血酶产生的血液室和血管平滑肌细胞（VSMC）的表面和脂肪因子，游离脂肪酸（FFA）和金属蛋白酶（MMPs）在肥胖Zucker大鼠的共同特点，人类代谢综合征的相互作用。方法：在25和80周龄时比较肥胖和年龄匹配的瘦Zucker大鼠。通过校准的自动血栓形成术（CAT）评估凝血酶的产生。结果：肥胖大鼠内源性凝血酶电位（ETP）升高，与血小板和年龄无关。血凝块半溶解时间随肥胖和年龄增加而延迟。白细胞介素（IL）-1β和IL-13分别随肥胖和增龄而升高。添加外源性纤维蛋白原，瘦素，亚油酸，棕榈酸增加血浆中凝血酶的产生，而脂联素有相反的效果。肥胖大鼠VSMCs表面的ETP增加，外源性棕榈酸进一步增强ETP值。明胶酶活性增加，在主动脉在两个年龄的肥胖大鼠和MMP-2活性增加，从肥胖大鼠的VSMCs。结论：我们的研究表明，在代谢综合征的早期血栓形成表型的血室加强促凝特性的去分化和炎症血管平滑肌细胞。机制涉及（1）纤维蛋白原增加和纤维蛋白溶解受损和（2）饱和脂肪酸增加，导致促凝血作用增加。是否专门针对这种高凝状态使用直接凝血酶抑制剂将改善MetS的结果是值得研究的。
Background: The metabolic syndrome (MetS) and aging are associated with modifications in blood coagulation factors, vascular inflammation, and increased risk of thrombosis. Objectives: Our aim was to determine concomitant changes in thrombin generation in the blood compartment and at the surface of vascular smooth muscle cells (VSMCs) and its interplay with adipokines, free fatty acids (FFA), and metalloproteinases (MMPs) in obese Zucker rats that share features of the human MetS. Methods: Obese and age-matched lean Zucker rats were compared at 25 and 80 weeks of age. Thrombin generation was assessed by calibrated automated thrombography (CAT). Results: Endogenous thrombin potential (ETP) was increased in obese rats independent of platelets and age. Clot half-lysis time was delayed with obesity and age. Interleukin (IL)-1β and IL-13 were increased with obesity and age respectively. Addition of exogenous fibrinogen, leptin, linoleic, or palmitic acid increased thrombin generation in plasma whereas adiponectin had an opposite effect. ETP was increased at the surface of VSMCs from obese rats and addition of exogenous palmitic acid further enhanced ETP values. Gelatinase activity was increased in aorta at both ages in obese rats and MMP-2 activity was increased in VSMCs from obese rats. Conclusions: Our study demonstrated in MetS an early prothrombotic phenotype of the blood compartment reinforced by procoagulant properties of dedifferentiated and inflammatory VSMCs. Mechanisms involved (1) increased fibrinogen and impaired fibrinolysis and (2) increased saturated fatty acids responsible for additive procoagulant effects. Whether specifically targeting this hypercoagulability using direct thrombin inhibitors would improve outcome in MetS is worth investigating.
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DOI：
10.1161/atvbaha.110.211946
发表时间：
2010-12-01
影响因子：
8.7
作者：
Beijers, Hanneke J. B. H.;Ferreira, Isabel;Stehouwer, Coen D. A.
通讯作者：
Stehouwer, Coen D. A.
DOI：
10.1183/09031936.00068712
发表时间：
2014-03
期刊：
The European respiratory journal
影响因子：
--
作者：
Firszt R;Francisco D;Church TD;Thomas JM;Ingram JL;Kraft M
通讯作者：
Kraft M
影响因子：
3.7
作者：
Godin, Jean-Philippe;Ross, Alastair B.;Kochhar, Sunil
通讯作者：
Kochhar, Sunil
影响因子：
15.9
作者：
Konstantinides, S;Schäfer, K;Loskutoff, DJ
通讯作者：
Loskutoff, DJ
影响因子：
6.1
作者：
Lu, Pei-pei;Liu, Jun-tian;Pang, Xiaoming
通讯作者：
Pang, Xiaoming