内皮
收缩性
CD36
生物
脂肪酸
内分泌学
脂肪组织
内科学
细胞生物学
基因
医学
生物化学
作者
Giulia Coppiello,María Collantes,Ma Salomé Sirerol-Piquer,Sara Vandenwijngaert,Sandra Schoors,Melissa Swinnen,Ine Vandersmissen,Paul Herijgers,Baki Topal,J. van Loon,Jan Goffin,Felipe Prósper,Peter Carmeliet,José Manuel García‐Verdugo,Stefan Janssens,Iván Peñuelas,Xabier L. Aranguren,Aernout Luttun
出处
期刊:Circulation
[Ovid Technologies (Wolters Kluwer)]
日期:2015-03-03
卷期号:131 (9): 815-826
被引量:88
标识
DOI:10.1161/circulationaha.114.013721
摘要
Microvascular endothelium in different organs is specialized to fulfill the particular needs of parenchymal cells. However, specific information about heart capillary endothelial cells (ECs) is lacking.Using microarray profiling on freshly isolated ECs from heart, brain, and liver, we revealed a genetic signature for microvascular heart ECs and identified Meox2/Tcf15 heterodimers as novel transcriptional determinants. This signature was largely shared with skeletal muscle and adipose tissue endothelium and was enriched in genes encoding fatty acid (FA) transport-related proteins. Using gain- and loss-of-function approaches, we showed that Meox2/Tcf15 mediate FA uptake in heart ECs, in part, by driving endothelial CD36 and lipoprotein lipase expression and facilitate FA transport across heart ECs. Combined Meox2 and Tcf15 haplodeficiency impaired FA uptake in heart ECs and reduced FA transfer to cardiomyocytes. In the long term, this combined haplodeficiency resulted in impaired cardiac contractility.Our findings highlight a regulatory role for ECs in FA transfer to the heart parenchyma and unveil 2 of its intrinsic regulators. Our insights could be used to develop new strategies based on endothelial Meox2/Tcf15 targeting to modulate FA transfer to the heart and remedy cardiac dysfunction resulting from altered energy substrate usage.
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