Heterocellular contact can dictate arterial function

Abstract

Resistance arteries use different dilatory heterocellular signaling mechanisms than conduit arteries (endothelial derived hyperpolarization versus nitric oxide). Anatomically, resistance arteries use myoendothelial junctions (MEJs), endothelial cell (EC) extensions that make contact with smooth muscle cells (SMCs), which are not present in conduit arteries. The objective of this study was to determine if the presence of MEJs in conduit arteries can alter heterocellular signaling. We previously demonstrated that plasminogen activator inhibitor‐1 (PAI‐1) can regulate formation of MEJs. Thus, we applied pluronic gel containing PAI‐1 directly to conduit arteries (carotid arteries, CAs) in live mice to determine if this could induce formation of MEJs. We found a significant increase in EC projections that resemble MEJs, correlating with increased biocytin dye transfer from ECs to SMCs and dilation to NS309. Next, we used pressure myography to investigate whether these structural changes were accompanied by a functional change in vasodilatory signaling. Interestingly, PAI‐1‐treated CAs underwent a switch from conduit to resistance artery vasodilatory profile via increased endothelial‐derived hyperpolarization (EDH) signaling and diminished nitric oxide (NO) signaling. Following PAI‐1 application, we also found a significant increase in carotid expression of endothelial alpha globin, a protein predominantly expressed in resistance arteries. Carotids from mice lacking alpha globin (Hba1−/−) demonstrated that L‐NAME, an inhibitor of NO signaling, was able to prevent vasodilation. Thus, the presence or absence of MEJs is an important determinant for protein expression to influence heterocellular communication. In particular, our data suggests that alpha globin may allow for EDH to predominate in resistance arteries.Support or Funding InformationThis work was supported by HL088554 (BEI) and the National Natural Science Foundation of China 81672945 (XHS).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.