Xiaochen Yuan1,2, Qingbin Wu1,2, Xueting Liu1,2, Honggang Zhang1,2, Ruijuan Xiu1,2. 1. Key Laboratory for Microcirculation, Ministry of Health Beijing, China. 2. Institute of Microcirculation, Chinese Academy Medical Sciences & Pecking Union Medical College Beijing, China.
Abstract
BACKGROUND: Changes in the structure and function of micro-vessels is the pathogenic basis of organ damage in cardiovascular and cerebrovascular diseases. Microcirculation is primarily affected in hypertension, resulting in increased vascular resistance. Pericytes are contractile cells that are embedded in the basement membrane of capillaries, and regulate endothelial cell membrane maturation, capillary blood flow, cell debris removal, and stability of endothelial cells. However, the exact role of brain microvascular pericytes in the pathogenesis of hypertension has not been elucidated. METHODS: Brain microvascular pericytes were isolated from spontaneously hypertensive rats (SHR) and wild type Wistar Kyoto (WKY) rats. The transcriptomes of SHR and WKY pericytes were analyzed by RNA-Seq, and the differentially expressed genes (DEGs) were screened by Ballgown, and Student's t test was used to be used to compare differences between groups. DAVID was used for the GO-enrichment analysis and KEGG pathway analysis of the DEGs, and an interaction network between the significant signaling pathways and DEGs was constructed. RESULTS: A total of 1356 DEGs were identified between the WKY and the SHR group pericytes (P value < 0.05, Fold change > 1.5), of which 733 were upregulated and 623 downregulated. The genes with greatest betweenness centrality values were Itgb1, Vcam-1 and MMP-9. Based on KEGG analysis, 34 interacting signaling pathways and 43 interacting genes were screened, and MAPK, p53, Wnt, Jak-STAT, TGF-beta, VEGF and PPAR signaling pathways were the key nodes. CONCLUSIONS: Several DEGs and signaling pathways were identified in the brain microvascular pericytes of SHR rats compared to the WKY rats. Our findings will lay the foundation to study the role of brain microvascular pericytes in the development of spontaneous hypertension.
BACKGROUND: Changes in the structure and function of micro-vessels is the pathogenic basis of organ damage in cardiovascular and cerebrovascular diseases. Microcirculation is primarily affected in hypertension, resulting in increased vascular resistance. Pericytes are contractile cells that are embedded in the basement membrane of capillaries, and regulate endothelial cell membrane maturation, capillary blood flow, cell debris removal, and stability of endothelial cells. However, the exact role of brain microvascular pericytes in the pathogenesis of hypertension has not been elucidated. METHODS: Brain microvascular pericytes were isolated from spontaneously hypertensiverats (SHR) and wild type Wistar Kyoto (WKY) rats. The transcriptomes of SHR and WKY pericytes were analyzed by RNA-Seq, and the differentially expressed genes (DEGs) were screened by Ballgown, and Student's t test was used to be used to compare differences between groups. DAVID was used for the GO-enrichment analysis and KEGG pathway analysis of the DEGs, and an interaction network between the significant signaling pathways and DEGs was constructed. RESULTS: A total of 1356 DEGs were identified between the WKY and the SHR group pericytes (P value < 0.05, Fold change > 1.5), of which 733 were upregulated and 623 downregulated. The genes with greatest betweenness centrality values were Itgb1, Vcam-1 and MMP-9. Based on KEGG analysis, 34 interacting signaling pathways and 43 interacting genes were screened, and MAPK, p53, Wnt, Jak-STAT, TGF-beta, VEGF and PPAR signaling pathways were the key nodes. CONCLUSIONS: Several DEGs and signaling pathways were identified in the brain microvascular pericytes of SHR rats compared to the WKY rats. Our findings will lay the foundation to study the role of brain microvascular pericytes in the development of spontaneous hypertension.
Authors: Li Fang; Yibing Yan; Laszlo G Komuves; Shirlee Yonkovich; Carol M Sullivan; Bradley Stringer; Sarah Galbraith; Nathalie A Lokker; S Stuart Hwang; Paquita Nurden; David R Phillips; Neill A Giese Journal: Arterioscler Thromb Vasc Biol Date: 2004-04 Impact factor: 8.311
Authors: Iain R Murray; James E Baily; William C W Chen; Ayelet Dar; Zaniah N Gonzalez; Andrew R Jensen; Frank A Petrigliano; Arjun Deb; Neil C Henderson Journal: Pharmacol Ther Date: 2016-09-02 Impact factor: 12.310