Impact of blood factors on endothelial cell metabolism and function in two diverse heart failure models.
Impact of blood factors on endothelial cell metabolism and function in two diverse heart failure models.
复制标题
DOI：
10.1371/journal.pone.0281550
复制
发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
基于血液的因素在心力衰竭（HF）的发展和进展中的作用尚不清楚。血液中含有病理生理状态下释放的因子，这些因子可能影响细胞功能，并为HF管理提供机制性见解。我们测试了两种不同HF模型的血液对心脏代谢的影响，并确定了可能的细胞靶点。从柔红霉素和心肌梗死诱导的HF兔（Dauno-HF和MI-HF）及其对照（Dauno-对照和MI-对照）中获得血浆。采用高分辨呼吸速率仪和Seahorse流量分析仪研究血浆对健康小鼠心肌组织和细胞心脏成分生物能量学的影响。由于内皮细胞呼吸受到HF血浆的深刻影响，因此进一步评价了血浆对内皮细胞屏障功能和死亡的影响。Western-blotting和电镜观察线粒体蛋白和形态。短暂暴露于HF血浆可降低心脏组织呼吸。暴露于HF血浆对内皮细胞呼吸的影响最大。与Dauno-HF血浆孵育后，内皮细胞单层完整性降低。Dauno-HF血浆孵育24 h后细胞凋亡和坏死增加。在Dauno-HF血浆暴露的细胞中观察到电压依赖性阴离子选择性通道（VDAC）-1、外膜转位酶20（Tom 20）和线粒体分裂因子（MFF）下调，在MI-HF血浆暴露的细胞中观察到线粒体信号转导子和转录激活子3（Stat 3）和MFF下调。暴露于HF血浆的细胞线粒体结构被破坏。这些发现表明，内皮细胞和线粒体结构和功能可能是HF病理表现和加速的主要目标。HF的高通量基于血液的筛查可以提供推进疾病诊断和管理的创新方法。
Role of blood-based factors in development and progression of heart failure (HF) is poorly characterized. Blood contains factors released during pathophysiological states that may impact cellular function and provide mechanistic insights to HF management. We tested effects of blood from two distinct HF models on cardiac metabolism and identified possible cellular targets of the effects. Blood plasma was obtained from daunorubicin- and myocardial infarction-induced HF rabbits (Dauno-HF and MI-HF) and their controls (Dauno-Control and MI-Control). Effects of plasma on bioenergetics of myocardial tissue from healthy mice and cellular cardiac components were assessed using high-resolution respirometry and Seahorse flux analyzer. Since endothelial cell respiration was profoundly affected by HF plasma, effects of plasma on endothelial cell barrier function and death were further evaluated. Western-blotting and electron microscopy were performed to evaluate mitochondrial proteins and morphology. Brief exposure to HF plasma decreased cardiac tissue respiration. Endothelial cell respiration was most impacted by exposure to HF plasma. Endothelial cell monolayer integrity was decreased by incubation with Dauno-HF plasma. Apoptosis and necrosis were increased in cells incubated with Dauno-HF plasma for 24 h. Down-regulation of voltage-dependent anion-selective channel (VDAC)-1, translocase of outer membrane 20 (Tom20), and mitochondrial fission factor (MFF) in cells exposed to Dauno-HF plasma and mitochondrial signal transducer and activator of transcription 3 (Stat3) and MFF in cells exposed to MI-HF plasma were observed. Mitochondrial structure was disrupted in cells exposed to HF plasma. These findings indicate that endothelial cells and mitochondrial structure and function may be primary target where HF pathology manifests and accelerates. High-throughput blood-based screening of HF may provide innovative ways to advance disease diagnosis and management.
登录
查看更多内容
影响因子：
7.4
作者：
Dranka, Brian P.;Hill, Bradford G.;Darley-Usmar, Victor M.
通讯作者：
Darley-Usmar, Victor M.
影响因子：
3.7
作者：
Ichikawa Y;Zemljic-Harpf AE;Zhang Z;McKirnan MD;Manso AM;Ross RS;Hammond HK;Patel HH;Roth DM
通讯作者：
Roth DM
影响因子：
3.5
作者：
Grip J;Jakobsson T;Tardif N;Rooyackers O
通讯作者：
Rooyackers O
影响因子：
37.8
作者：
Agnoletti, L;Curello, S;Ferrari, R
通讯作者：
Ferrari, R
影响因子：
3.4
作者：
McCommis, Kyle S.;Baines, Christopher P.
通讯作者：
Baines, Christopher P.