Complement 5a Receptor deficiency does not influence adverse cardiac remodeling after pressure-overload in mice.
Complement 5a Receptor deficiency does not influence adverse cardiac remodeling after pressure-overload in mice.
复制标题
DOI：
10.1038/s41598-017-16957-3
复制
发表时间：
2017-12-06
影响因子：
4.6
通讯作者：
de Jager SCA
中科院分区：
文献类型：
--
作者：
de Haan JJ;Bosch L;Borgman A;Bastemeijer M;Brans MAD;van de Weg SM;de Kleijn DPV;Sluijter JPG;El Azzouzi H;de Jager SCA
高血压是普通人群中发生心力衰竭最常见的危险因素之一。炎症在这种不利的重塑中起着核心作用，并最终导致心力衰竭的发展。高血压患者循环中补体因子5a(C5a)水平升高，在实验性高血压模型中，C5a受体与心脏纤维化和炎症的存在有关。为了验证C5aR是否参与压力超负荷后心脏的不良重构，我们建立了野生型和C5a受体缺陷小鼠(C5aR−/−)的横动脉缩窄模型(TAC)，在TAC后6周内，C5aR-/-动物表现出与野生型小鼠相似的心肌肥厚和心功能下降(收缩末期容量：50.30±5.32 L vs.55.81±8.16 L)。此外，心肌细胞大小(WGA染色)、纤维化(天狼星红染色)或胶原降解(基质金属蛋白酶活性测定)等不良心脏重塑的其他特征也没有差别。综上所述，全身C5aR缺乏不会影响压力超负荷后心脏的不良重构。然而，我们的发现与C5a抑制研究相反。我们的观察显示，C5a-C5aR在不良心脏重塑和心力衰竭中的作用至少是有争议的。
Hypertension is one of the most common risk factors for the development heart failure in the general population. Inflammation plays a central role in this adverse remodeling and eventually to the development of heart failure. Circulating levels of Complement factor 5a (C5a) are increased in hypertensive patients and the C5a receptor is associated with the presence of cardiac fibrosis and inflammation in an experimental hypertension model. To test if C5aR is involved in adverse cardiac remodeling following pressure-overload, we induced transverse aortic constriction (TAC) in wildtype and C5a receptor deficient mice (C5aR−/−). Six weeks after TAC, C5aR-/- animals showed a similar degree of cardiac hypertrophy and decrease in cardiac function as wild type mice (End Systolic Volume; 50.30±5.32 µl vs. 55.81±8.16 µl). In addition, other features of adverse cardiac remodeling like cardiomyocyte cell size (WGA staining), fibrosis (picrosirius red staining) or collagen degradation (matrix metalloproteinase activity assay) did not differ either. In conclusion, full body C5aR deficiency does not affect adverse cardiac remodeling after pressure-overload. However, our finding are in contrast with C5a inhibition studies. Our observations do present the role of C5a-C5aR in adverse cardiac remodeling and heart failure as controversial at the least.
登录
查看更多内容
影响因子：
49.6
作者：
Bui, Anh L.;Horwich, Tamara B.;Fonarow, Gregg C.
通讯作者：
Fonarow, Gregg C.
影响因子：
7.5
作者：
Deng Y;Zhao H;Zhou J;Yan L;Wang G;China HepB-Related Fibrosis Assessment Research Group
通讯作者：
China HepB-Related Fibrosis Assessment Research Group
DOI：
10.1161/circheartfailure.115.002225
发表时间：
2015-07
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Nevers T;Salvador AM;Grodecki-Pena A;Knapp A;Velázquez F;Aronovitz M;Kapur NK;Karas RH;Blanton RM;Alcaide P
通讯作者：
Alcaide P
C5aR 拮抗剂可预防血管紧张素 II 诱发的高血压中的心脏重塑
影响因子：
3.2
作者：
Zhang, Congcong;Li, Yulin;Du, Jie
通讯作者：
Du, Jie
影响因子：
20.3
作者：
Langer, Harald F.;Chung, Kyoung-Jin;Chavakis, Triantafyllos
通讯作者：
Chavakis, Triantafyllos