Coronary artery remodeling in a model of left ventricular pressure overload is influenced by platelets and inflammatory cells.
Coronary artery remodeling in a model of left ventricular pressure overload is influenced by platelets and inflammatory cells.
复制标题
左心室压力超负荷模型中的冠状动脉重塑受到血小板和炎症细胞的影响。
DOI：
10.1371/journal.pone.0040196
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Smyth SS
中科院分区：
文献类型：
--
作者：
Yang F;Dong A;Mueller P;Caicedo J;Sutton AM;Odetunde J;Barrick CJ;Klyachkin YM;Abdel-Latif A;Smyth SS
左心室肥厚（LVH）常伴有严重的间质和血管周围纤维化，可能导致心源性猝死。心脏纤维化发生的机制尚不完全清楚。为了研究血管周围炎症在肥厚性心室重构过程中冠状动脉重构和心脏纤维化中的作用，我们使用了一种成熟的LVH（横向主动脉缩窄[TAC]）小鼠模型。压力超负荷后3天，巨噬细胞和T淋巴细胞聚集在左冠状动脉周围和沿着，并伴有管腔血小板沉积。与这些组织学发现一致，与假手术对照组相比，TAC动物中IL-10的心脏表达上调，并且在体循环中，血小板白色血细胞聚集倾向于更高。由于血小板可以动态调节血管周围炎症，我们研究了血小板减少对TAC反应的影响。血小板的免疫耗竭减少了早期血管周围T淋巴细胞的积聚，并改变了随后的冠状动脉重塑。在Rag 1 −/−小鼠中检查了淋巴细胞的贡献，与TAC后的野生型小鼠相比，Rag 1 −/−小鼠显示出显著更多的内膜增生和血管周围纤维化。总的来说，我们的研究支持血小板和T淋巴细胞在压力超负荷诱导的炎症中的早期血管周围积聚的作用。
Left ventricular hypertrophy (LVH) is usually accompanied by intensive interstitial and perivascular fibrosis, which may contribute to arrhythmogenic sudden cardiac death. The mechanisms underlying the development of cardiac fibrosis are incompletely understood. To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of LVH (transverse aortic constriction [TAC]). Three days after pressure overload, macrophages and T lymphocytes accumulated around and along left coronary arteries in association with luminal platelet deposition. Consistent with these histological findings, cardiac expression of IL-10 was upregulated and in the systemic circulation, platelet white blood cell aggregates tended to be higher in TAC animals compared to sham controls. Since platelets can dynamically modulate perivascular inflammation, we investigated the impact of thrombocytopenia on the response to TAC. Immunodepletion of platelets decreased early perivascular T lymphocytes' accumulation and altered subsequent coronary artery remodeling. The contribution of lymphocytes were examined in Rag1−/− mice, which displayed significantly more intimal hyperplasia and perivascular fibrosis compared to wild-type mice following TAC. Collectively, our studies support a role of early perivascular accumulation of platelets and T lymphocytes in pressure overload-induced inflammation.