2026-06-14T03:30:03Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/67292024-10-31T11:52:53Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
advisor
de la Pompa, Jose Luis
advisor
MacGrogan, Donal
author
Travisano, Stanislao Igor
funder
Ministerio de Economía y Competitividad (España)
funder
Centro de Investigación Biomedica en Red - CIBER
2018-11-28T11:18:30Z
2018-11-28T11:18:30Z
2018-10-15
10.4321/repisalud.6729
http://hdl.handle.net/20.500.12105/6729
Coronary vessels supply the myocardium with nutrients and oxygen and are crucial
for heart development and function. Coronary development defects result in coronary disease, a major cause of morbidity and mortality worldwide. The Notch signaling pathway is a highly conserved pathway, crucial for the regulation of cell specification and proliferation in specific tissue and organs. Specifically, the Notch pathway regulates the processes leading to the formation of the ventricular chambers; trabeculation, coronary vessel formation and trabecular compaction.ng. Later induced loss of Jag1 or Dll4 or gain of Dll4 or MFng leads to defective arterial specification, vascular malformations and aberrant coronary arterial patterning. Loss of Ephrinb2 phenocopies loss Jag1, and Ephrinb2 can rescue defective angiogenesis of Jag1- and Dll4-inactivated ventricular explants, identifying Ephrinb2 as a target of both ligands during coronary artery formation. Thus, Jag1 and Dll4/MFng have early opposing roles and late cooperative roles in coronary formation and the downstream direct target Ephrinb2 in endothelium and endocardium is a key effector molecule for the coronary arterial morphogenesis. Comparative transcriptome profiling of the different loss and gain of function
mutant hearts revealed hypoxic, oxidative stress and cell death pathways and the activation of immune-inflammatory responses suggestive of ischaemic cell death. Thus perturbation of endocardial/endothelial Notch signaling severely disrupts coronary development and consequently myocardium proliferation and compaction, resulting in embryonic lethality. This implies that development of the coronary vessels and growth and maturation of the ventricles are two interlinked Notch-dependent processes.
eng
notch
angiogenesis
cardiovascular
heart
Role of Notch Signaling in Coronary Vessel Angiogenesis and Remodelling
doctoral thesis
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
URL
https://repisalud.isciii.es/bitstreams/0d136311-fbb2-4103-9cf0-51c10baa2d64/download
File
MD5
db69c243b9a269a3e4c2855dc43ae2b0
430952811
application/pdf
Thesis StanislaoIgorTravisano.pdf
URL
https://repisalud.isciii.es/bitstreams/8cad3165-bcde-4625-9b0e-89395d1b96af/download
File
MD5
40a63a3b939b3664a969e1ca14ab02db
79701
application/vnd.openxmlformats-officedocument.wordprocessingml.document
Suppl.Table 1 .docx
URL
https://repisalud.isciii.es/bitstreams/f2f1571f-4be2-4bdf-89e6-fc705840da59/download
File
MD5
5a15c56c77c347859c6f0308a386a999
167370
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
Suppl.Table 2.xlsx
URL
https://repisalud.isciii.es/bitstreams/96a9e8bb-1fde-49a2-857f-e1c271de0766/download
File
MD5
bd89cc52c00dec3152f5b34e12e5c589
210432
application/vnd.ms-excel
Suppl.Table 3.xls
URL
https://repisalud.isciii.es/bitstreams/1f94118d-0ca3-4f11-aed1-c6169fa898ec/download
File
MD5
6807ed332a4c6373dfc868b7a7ff56d0
62355
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
Suppl.Table 4.xlsx
URL
https://repisalud.isciii.es/bitstreams/99d623a5-e74b-47d6-94f9-cd4af8838f4b/download
File
MD5
18133b2239487cbb315e014a6f9d700f
87522
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
Suppl.Table 5.xlsx
URL
https://repisalud.isciii.es/bitstreams/fcb39a1b-edc4-4be1-9201-bfeb973eddae/download
File
MD5
a8ab179d15aceb0d47d43ac025948132
205854
text/plain
Thesis StanislaoIgorTravisano.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/2162b512-27c2-49cb-ba34-1873bd4f0ec3/download
File
MD5
fcda6072e2e37448e9666769e1330d2c
3370
text/plain
Suppl.Table 1 .docx.txt
URL
https://repisalud.isciii.es/bitstreams/94c06b9a-8bc5-493d-8ad6-66270d31f0d5/download
File
MD5
9ecd0bb136f369a3c9669394688bbb34
100000
text/plain
Suppl.Table 2.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/c58bf212-c688-4783-aae3-e3c58ed841df/download
File
MD5
eafad9430c6357e8be8b48f33c6b8831
100000
text/plain
Suppl.Table 3.xls.txt
URL
https://repisalud.isciii.es/bitstreams/8027e19a-f3ef-408c-9fa3-5457659de05a/download
File
MD5
609f3294558d5388d815186a18d226c4
71884
text/plain
Suppl.Table 4.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/fb9225f6-01dd-4e9f-8665-db120fa47793/download
File
MD5
d5fd2037f5a4faeba8ec96977c9494a3
67598
text/plain
Suppl.Table 5.xlsx.txt