Distinct Vascular Remodeling Pattern of Adult Rats with Carotid-Jugular Shunt

Abstract

Previous research has revealed that patent vein grafts lose their venous identity Eph-B4 but do not gain arterial identity ephrin-B2 during adaptation to the arterial circulation, and vascular identity marker, for example, the Eph-B4 signaling is a critical determinant of venous wall thickness of vein grafts. But what is the remodeling pattern, especially the remodeling pattern of vascular identity in the venous segment of arteriovenous shunt at a late stage postoperation has not been fully explored. This study was conducted to characterize the remodeling pattern of shear stress, vascular identity, structural composition and morphology, and transcriptional profiles in jugular segment of carotid-jugular (CJ) shunt and/or pulmonary artery (PA), which delivers an increased amount of mixed blood at a late stage postoperation in adult rats. CJ shunt was created in adult Wistar rats via end-to-end anastomosis of carotid artery (CA) and jugular vein (JV). At the time of 15weeks, after hemodynamics test, remodeled jugular segment of CJ shunt, PA, and sham-operated corresponding vessels were isolated. Reverse transcription polymerase chain reaction, microarray, western blot, immunohistochemistry experiments, and morphology analyses were performed. CJ shunt shear stresses have been patterned to some sort of balance with no significant difference in shear stress between carotid segment and jugular segment (P>0.05). Immunohistochemical analysis reveals that venous identity marker Eph-B4 is lost, but arterial identity markers ephrin-B2 and regulator of G-protein signaling 5 are gained in jugular segment of CJ shunt (P<0.01), and these 2 arterial identity markers further strengthened in PA (P<0.01) in shunted rats compared with controls. Jugular segment of CJ shunt undergoes significant intimal hyperplasia with strong expression of smooth muscle cell markers (P<0.05) and demonstrates a distinct transcriptional profiles which reveals that transcripts of 5 arterial markers are significantly upregulated (P<0.05 or<0.01) compared with sham-operated JV; among them, G-protein signaling 5 is exactly the gene with the largest fold change (10.14-fold) in all genes tested by microarray experiment. Venous identity is lost, but arterial identity is gained in jugular segment of CJ shunt and arterial identity further strengthened in PA in adult shunted rats during late adaptation.