Fig. 6.

Noncoding sequence control of vascular cell phenotypes. The differentiated phenotype of Weibel-Palade body (WP-b) containing ECs (top electron micrograph) and subjacent, Myofilament (Mf)-containing SMCs (bottom electron micrograph) is regulated through TFBS (such as ETS and CArG elements, respectively), directing expression of mRNA, miR, and lncRNA genes whose mature products serve structural and complex regulatory roles, the latter likely involving direct or indirect effects of each transcribed unit on other transcribed sequences in the nucleus or cytoplasm (small arrows). TFBS-SNPs (denoted with an X in each element) may interfere with normal target gene expression and hence perturb the differentiated vascular cell phenotype. Intercellular control of vascular cell phenotypes (large arrows) may be achieved through the action of RNA-containing extracellular vesicles (e.g., exosomes denoted as small circles released locally in the interstitial space or via circulation in the case of ECs)