Systematic Analysis of the Smooth Muscle Wall Phenotype of the Pharyngeal Arch Arteries During Their Reorganization into the Great Vessels and Its Association with Hemodynamics

Abstract

Early outflow morphogenesis is a critical event in cardiac development. Understanding the mechanical and molecular based morphogenetic relationships at early stages of cardiogenesis is essential for the advancement of cardiovascular technology related to congenital heart defects. In this study, we pair molecular changes in pharyngeal arch artery (PAA) vascular smooth muscle cells (VSMCs) and hemodynamic changes throughout development. We focus on Hamburger Hamilton stage 24 to 36 chick embryos, using both Doppler ultrasound and histological sections to phenotype PAA VSMCs, and establish a relationship between hemodynamics and PAA composition. Our findings show that PAA VSMCs transition through a synthetic, intermediate, and contractile phenotype over time. Wall shear stress magnitude per arch varies throughout development. Despite these distinct hemodynamic and fractional expression trends, no strong correlation exists between the two, indicating that WSS magnitude is not the main driver of PAA wall remodeling and maturation. While WSS magnitude was not found to be a major driver, this work provides a basic framework for investigating relationships between hemodynamic forces and tunica media during a critical period of development.

Cyclic tensile strain facilitates proliferation and migration of human aortic smooth muscle cells and reduces their apoptosis via miRNA-187-3p

“…In cardiovascular diseases such as hypertension, aortic coarctation, lumen narrowing and atherosclerosis accompanied by revascularization, these changes in vascular structure and function involve phenotypic changes in VSMCs [ 35 , 36 ]. Hemodynamic factors have an important influence on the morphology, structure and function of vascular cells, and the phenotype of VSMCs changes accordingly with changes in the mechanical environment, thus affecting the structure and function of the vessel wall [ 37 , 38 ]. In this study, we applied 5%, 10% and 15% CTS to HASMCs and detected DE-miRNAs in HASMCs in response to CTS by RNA-seq, and verified the effects of CTS and miRNAs on HASMCs phenotype.…”

The State of Cardiovascular Developmental Biology is Strong — Honoring Dr. Roger Markwald and his Seminal Contributions to the Field

“…Jessica Ryvlin (undergraduate student) and Stephanie Lindsey (PhD student), members of the laboratory of Jonathan Butcher, are cofirst author on a paper that discusses the molecular changes in pharyngeal arch artery (PAA) and vascular smooth muscle cells and hemodynamic changes throughout development. Based on the data obtained, they conclude that wall shear stress does not play a significant role in the remodeling and maturation of the PAA and hypothesize that pressure and inherent wall tissue stress may play a larger role in these events (Ryvlin et al, ).…”