Hyperglycemia-induced PATZ1 negatively modulates endothelial vasculogenesis via repression of FABP4 signaling.
Vascular endothelial dysfunction, a central hallmark of diabetes, predisposes diabetic patients to numerous cardiovascular complications. The POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1), is an important transcriptional regulatory factor and regulates divergent pathways depending on the cellular context, but its role in endothelial cells remains poorly understood. Herein, we report for the first time that endothelial PATZ1 expression was abnormally upregulated in diabetic endothelial cells (ECs) regardless of diabetes classification. This stimulatory effect was further confirmed in the high glucose-treated human umbilical vein endothelial cells (HUVECs). From a functional standpoint, transgenic overexpression of PATZ1 in endothelial colony forming cells (ECFCs) blunted angiogenesis in vivo and rendered endothelial cells unresponsive to established angiogenic factors. Mechanistically, PATZ1 acted as a potent transcriptional corepressor of fatty acid-binding protein 4 (FABP4), an essential convergence point for angiogenic and metabolic signaling pathways in ECs. Taken together, endothelial PATZ1 thus potently inhibits endothelial function and angiogenesis via inhibition of FABP4 expression, and abnormal induction of endothelial PATZ1 may contribute to multiple aspects of vascular dysfunction in diabetes.
Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
Ren-An
RA
Chen
Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Xiao-Mian
XM
Sun
Xi'an Health Management Service Center, Xi'an, 710032, China.
Chang-You
CY
Yan
Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
Li
L
Liu
Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
Miao-Wang
MW
Hao
Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
Qiang
Q
Liu
Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China. Electronic address: sscwjg@fmmu.edu.cn.
Xi-Ying
XY
Jiao
Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China. Electronic address: Liangyingmintd@yeah.net.
Ying-Min
YM
Liang
D000818:Animals; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction
C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C485875:Zfp278 protein, mouse; D005947:Glucose
Angiogenesis; Diabetes; Endothelial cells; FABP4; PATZ1