Epicardial adipose excision slows the progression of porcine coronary atherosclerosis.

Epicardial adipose excision slows the progression of porcine coronary atherosclerosis.
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DOI:
10.1186/1749-8090-9-2
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发表时间:
2014-01-03
影响因子:
1.6
通讯作者:
Sturek M
Sturek M
中科院分区:
医学4区
文献类型:
--
作者:
McKenney ML;Schultz KA;Boyd JH;Byrd JP;Alloosh M;Teague SD;Arce-Esquivel AA;Fain JN;Laughlin MH;Sacks HS;Sturek M

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在人类中,心外膜脂肪组织(EAT)体积与冠状动脉粥样硬化(CAD)负荷之间存在正相关性。我们在猪模型中检验了EAT局部促成CAD的假设。Ossabaw小型猪(n = 9)被喂食致动脉粥样硬化饮食6个月以产生CAD。在左前降支(LAD)中段左主分叉远端15 mm处进行了15 mm长× 3-5 mm宽的冠状动脉EAT(cEAT)切除术。猪在致动脉粥样硬化饮食中恢复3个月。在脂肪切除术后立即在LAD中进行血管内超声(IVUS)以量化粥样硬化,并在处死前恢复后重复。冠状动脉壁活检组织进行动脉粥样硬化标记物和细胞因子的化学染色,并通过RT-PCR检测动脉粥样硬化相关基因的cEAT。在每次IVUS之前通过非造影CT测量总EAT体积。从基线到处死,LAD近端和远端段的周向斑块长度增加(p < 0.05),而在脂肪切除部位下方的LAD中段的斑块长度没有增加。T-钙粘蛋白、清道夫受体A和脂联素在左前降支中段壁内减少。相对于无CAD的对照猪,cEAT中11β-羟基类固醇脱氢酶(11βHSD-1)、CCL 19、CCL 21、前列腺素D2合酶、gp 91 phox [NADPH氧化酶]、VEGF、VEGFGR 1和血管紧张素原mRNA上调。EAT体积在3个月内增加。在作为其自身对照的猪中,切除cEAT可降低CAD的进展,表明cEAT可能加剧冠状动脉粥样硬化。
In humans there is a positive association between epicardial adipose tissue (EAT) volume and coronary atherosclerosis (CAD) burden. We tested the hypothesis that EAT contributes locally to CAD in a pig model. Ossabaw miniature swine (n = 9) were fed an atherogenic diet for 6 months to produce CAD. A 15 mm length by 3–5 mm width coronary EAT (cEAT) resection was performed over the middle segment of the left anterior descending artery (LAD) 15 mm distal to the left main bifurcation. Pigs recovered for 3 months on atherogenic diet. Intravascular ultrasound (IVUS) was performed in the LAD to quantify atheroma immediately after adipectomy and was repeated after recovery before sacrifice. Coronary wall biopsies were stained immunohistochemically for atherosclerosis markers and cytokines and cEAT was assayed for atherosclerosis-related genes by RT-PCR. Total EAT volume was measured by non-contrast CT before each IVUS. Circumferential plaque length increased (p < 0.05) in the proximal and distal LAD segments from baseline until sacrifice whereas plaque length in the middle LAD segment underneath the adipectomy site did not increase. T-cadherin, scavenger receptor A and adiponectin were reduced in the intramural middle LAD. Relative to control pigs without CAD, 11β-hydroxysteroid dehydrogenase (11βHSD-1), CCL19, CCL21, prostaglandin D2 synthase, gp91phox [NADPH oxidase], VEGF, VEGFGR1, and angiotensinogen mRNAs were up-regulated in cEAT. EAT volume increased over 3 months. In pigs used as their own controls, resection of cEAT decreased the progression of CAD, suggesting that cEAT may exacerbate coronary atherosclerosis.
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