PDF(Pubmed)
Abstract：
The luminal surface of the endothelium is exposed to dynamic blood flow patterns that are known to affect endothelial cell phenotype. While many studies have documented the phenotypic changes by gene or protein expression, less is known about the role of blood flow pattern on the endothelial cell (EC) lipidome. In this study, shotgun lipidomics was conducted on human aortic ECs (HAECs) exposed to unidirectional laminar flow (UF), disturbed flow (DF), or static conditions for 48 h. A total of 520 individual lipid species from 17 lipid subclasses were detected. Total lipid abundance was significantly increased for HAECs exposed to DF compared to UF conditions. Despite the increase in the total lipid abundance, HAECs maintained equivalent composition of each lipid subclass (% of total lipid) under DF and UF. However, by lipid composition (% of total subclass), 28 lipid species were significantly altered between DF and UF. Complimentary RNA sequencing of HAECs exposed to UF or DF revealed changes in transcripts involved in lipid metabolism. Shotgun lipidomics was also performed on HAECs exposed to pro-inflammatory agonists lipopolysaccharide (LPS) or Pam3CSK4 (Pam3) for 48 h. Exposure to LPS or Pam3 reshaped the EC lipidome in both unique and overlapping ways. In conclusion, exposure to flow alters the EC lipidome and ECs undergo stimulus-specific lipid reprogramming in response to pro-inflammatory agonist exposure. Ultimately, this work provides a resource to profile the transcriptional and lipidomic changes that occur in response to applied flow that can be accessed by the vascular biology community to further dissect and extend our understanding of endothelial lipid biology.
摘要：
内皮的腔表面暴露于已知影响内皮细胞表型的动态血流模式。虽然许多研究已经记录了基因或蛋白质表达的表型变化，关于血流模式对内皮细胞（EC）脂质的作用知之甚少。在这项研究中,shot弹枪脂质组学在暴露于单向层流（UF）的人主动脉EC（HAEC）上进行，扰动流（DF），或静态条件48小时。总共检测到来自17个脂质亚类的520个单独的脂质种类。与UF条件相比，暴露于DF的HAEC的总脂质丰度显着增加。尽管总脂质丰度增加，HAEC在DF和UF下保持每个脂质亚类的等效组成（占总脂质的％）。然而,按脂质组成（占总亚类的百分比），DF和UF之间的28种脂质发生了显着变化。暴露于UF或DF的HAEC的补充RNA测序显示了与脂质代谢有关的转录本的变化。还对暴露于促炎激动剂脂多糖（LPS）或Pam3CSK4（Pam3）48小时的HAECs进行了Shotgun脂质组学。暴露于LPS或Pam3以独特和重叠的方式重塑了EC脂质组。总之,暴露于流改变了EC脂质组,并且EC响应于促炎激动剂暴露而经历刺激特异性脂质重编程。最终,这项工作提供了一个资源来描述转录和脂质组学变化，这些变化是响应于应用流而发生的，血管生物群落可以访问这些变化，以进一步剖析和扩展我们对内皮脂质生物学的理解。
