Wilson Caitlin, Thompson Janice M, Terrian Leah, Lauver Adam D, Flood Emma D, Fink Gregory D, Sather Lisa, Bhattacharya Sudin, Contreras G Andres, Watts Stephanie W
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA.
Department of Biomedical Engineering, Michigan State University, East Lansing, Michigan, USA.
J Vasc Res. 2024;61(1):26-37. doi: 10.1159/000535513. Epub 2023 Dec 19.
Tunica media extracellular matrix (ECM) remodeling is well understood to occur in response to elevated blood pressure, unlike the remodeling of other tunicas. We hypothesize that perivascular adipose tissue (PVAT) is responsive to hypertension and remodels as a protective measure.
The adventitia and PVAT of the thoracic aorta were used in measuring ECM genes from 5 pairs of Dahl SS male rats on 8 or 24 weeks of feeding from weaning on a control (10% Kcal fat) or high-fat (HF; 60%) diet. A PCR array of ECM genes was performed with cDNA from adventitia and PVAT after 8 and 24 weeks. A gene regulatory network of the differentially expressed genes (DEGs) (HF 2-fold > con) was created using Cytoscape.
After 8 weeks, 29 adventitia but 0 PVAT DEGs were found. By contrast, at 24 weeks, PVAT possessed 47 DEGs while adventitia had 3. Top DEGs at 8 weeks in adventitia were thrombospondin 1 and collagen 8a1. At 24 weeks, thrombospondin 1 was also a top DEG in PVAT. The transcription factor Adarb1 was identified as a regulator of DEGs in 8-week adventitia and 24-week PVAT.
These data support that PVAT responds biologically once blood pressure is elevated.
与其他血管层的重塑不同,人们清楚地知道中膜细胞外基质(ECM)重塑是对血压升高的一种反应。我们假设血管周围脂肪组织(PVAT)对高血压有反应,并作为一种保护措施进行重塑。
使用断奶后分别喂食对照(10%千卡脂肪)或高脂(HF;60%)饮食8周或24周的5对Dahl SS雄性大鼠的胸主动脉外膜和PVAT来测量ECM基因。在8周和24周后,用外膜和PVAT的cDNA进行ECM基因的PCR阵列分析。使用Cytoscape创建差异表达基因(DEGs)(HF比对照高2倍)的基因调控网络。
8周后,在外膜发现了29个差异表达基因,但在PVAT中未发现。相比之下,在24周时,PVAT有47个差异表达基因,而外膜有3个。外膜在8周时的顶级差异表达基因是血小板反应蛋白1和胶原蛋白8a1。在24周时,血小板反应蛋白1也是PVAT中的顶级差异表达基因。转录因子Adarb1被确定为8周外膜和24周PVAT中差异表达基因的调节因子。
这些数据支持一旦血压升高,PVAT会发生生物学反应。