Serum Response Factor involvement in myogenic tone regulation in resistance arteries

Abstract

Serum Response Factor(SRF) is a transcription factor playing a crucial role in the control of cell cytoskeletal structure. Actin dynamics and RhoA activity are major players in SRF transcriptional activity. In the microcirculation, diameter adjustments in response to change in pressure or flow depend on cytoskeleton integrity. Thus, we hypothesised that SRF deletion will affect mechanotransduction in resistance arteries. Tail caudal arteries from inducible SRF KO mice and control mice were mounted in an arteriograph. Contraction to stepwise increase in pressure (myogenic tone) and relaxation to stepwise increases in flow were determined. Protein expressions were quantificated by western blot. SRF deficiency reduced myogenic tone (CT:16.3±3.2; KO:5.9±2.3) and increased Focal Adhesion Kinase (FAK)(CT:0,23±0,03/KO:0,16±0,02) while P‐FAK/FAK ratio was similar in both groups. Furthermore, no effect was observed in flow‐mediated dilation and receptor dependant contraction (phenylephrine and angiotensine II). This study reported for the first time that SRF inhibition affected specifically myogenic tone. This suggests that SRF is involved in the pressure mechanotransduction in resistance arteries. Due to the central role of myogenic tone in vascular disorders and organs autoregulation this finding opens new perspectives in microcirculation pathophysiology and provides new therapeutic targets.