RT Journal Article
T1 CCN2 (Cellular Communication Network Factor 2) Deletion Alters Vascular Integrity and Function Predisposing to Aneurysm Formation
A1 Rodrigues Díez, Raúl
A1 Rodrigues Díez, Raquel
A1 Ruiz Ortega, Marta
AB Background:CCN2 (cellular communication network factor 2) is a matricellular protein involved in cell communication and microenvironmental signaling responses. CCN2 is known to be overexpressed in several cardiovascular diseases, but its role is not completely understood.Methods:Here, CCN2 involvement in aortic wall homeostasis and response to vascular injury was investigated in inducible Ccn2-deficient mice, with induction of vascular damage by infusion of Ang II (angiotensin II; 15 days), which is known to upregulate CCN2 expression in the aorta.Results:Ang II infusion in CCN2-silenced mice lead to 60% mortality within 10 days due to rapid development and rupture of aortic aneurysms, as evidenced by magnetic resonance imaging, echography, and histological examination. Ccn2 deletion decreased systolic blood pressure and caused aortic structural and functional changes, including elastin layer disruption, smooth muscle cell alterations, augmented distensibility, and increased metalloproteinase activity, which were aggravated by Ang II administration. Gene ontology analysis of RNA sequencing data identified aldosterone biosynthesis as one of the most enriched terms in CCN2-deficient aortas. Consistently, treatment with the mineralocorticoid receptor antagonist spironolactone before and during Ang II infusion reduced aneurysm formation and mortality, underscoring the importance of the aldosterone pathway in Ang II–induced aorta pathology.Conclusions:CCN2 is critically involved in the functional and structural homeostasis of the aorta and in maintenance of its integrity under Ang II–induced stress, at least, in part, by disruption of the aldosterone pathway. Thus, this study opens new avenues to future studies in disorders associated to vascular pathologies.
PB Lippincott Williams & Wilkins
SN 0194-911X
YR 2021
FD 2021-12-30
LK https://hdl.handle.net/20.500.14352/116485
UL https://hdl.handle.net/20.500.14352/116485
LA eng
NO Rodrigues-Díez RR, Tejera-Muñoz A, Esteban V, Steffensen LB, Rodrigues-Díez R, Orejudo M, Rayego-Mateos S, Falke LL, Cannata-Ortiz P, Ortiz A, Egido J, Mallat Z, Briones AM, Bajo MA, Goldschmeding R, Ruiz-Ortega M. CCN2 (Cellular Communication Network Factor 2) Deletion Alters Vascular Integrity and Function Predisposing to Aneurysm Formation. Hypertension. 2022 Mar;79(3):e42-e55. doi: 10.1161/HYPERTENSIONAHA.121.18201
DS Docta Complutense
RD 7 abr 2025