Mechanisms of Amplified Arteriogenesis in Collateral Artery Segments Exposed to Reversed Flow Direction

Arteriosclerosis, Thrombosis, and Vascular Biology
Joshua L HeusleinRichard J Price

Abstract

Collateral arteriogenesis, the growth of existing arterial vessels to a larger diameter, is a fundamental adaptive response that is often critical for the perfusion and survival of tissues downstream of chronic arterial occlusion(s). Shear stress regulates arteriogenesis; however, the arteriogenic significance of reversed flow direction, occurring in numerous collateral artery segments after femoral artery ligation, is unknown. Our objective was to determine if reversed flow direction in collateral artery segments differentially regulates endothelial cell signaling and arteriogenesis. Collateral segments experiencing reversed flow direction after femoral artery ligation in C57BL/6 mice exhibit increased pericollateral macrophage recruitment, amplified arteriogenesis (30% diameter and 2.8-fold conductance increases), and remarkably permanent (12 weeks post femoral artery ligation) remodeling. Genome-wide transcriptional analyses on human umbilical vein endothelial cells exposed to reversed flow conditions mimicking those occurring in vivo yielded 10-fold more significantly regulated transcripts, as well as enhanced activation of upstream regulators (nuclear factor κB [NFκB], vascular endothelial growth factor, fibroblast growth ...Continue Reading

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Citations

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