Engineering Smooth Muscle to Understand Extracellular Matrix Remodeling and Vascular Disease

Abstract

The vascular smooth muscle is vital for regulating blood pressure and maintaining cardiovascular health, and the resident smooth muscle cells (SMCs) in blood vessel walls rely on specific mechanical and biochemical signals to carry out these functions. Any slight change in their surrounding environment causes swift changes in their phenotype and secretory profile, leading to changes in the structure and functionality of vessel walls that cause pathological conditions. To adequately treat vascular diseases, it is essential to understand how SMCs crosstalk with their surrounding extracellular matrix (ECM). Here, we summarize in vivo and traditional in vitro studies of pathological vessel wall remodeling due to the SMC phenotype and, conversely, the SMC behavior in response to key ECM properties. We then analyze how three-dimensional tissue engineering approaches provide opportunities to model SMCs’ response to specific stimuli in the human body. Additionally, we review how applying biomechanical forces and biochemical stimulation, such as pulsatile fluid flow and secreted factors from other cell types, allows us to study disease mechanisms. Overall, we propose that in vitro tissue engineering of human vascular smooth muscle can facilitate a better understanding of relevant cardiovascular diseases using high throughput experiments, thus potentially leading to therapeutics or treatments to be tested in the future.

A Modified Protocol for the Isolation, Culture, and Characterization of Human Smooth Muscle Cells from the Umbilical Cord

“…For example, for the characterization part, collagen was specifically used to coat culture ware instead of gelatin, and serum-reduced medium and heparin were added to ensure that the cells were in the contractile state. This was confirmed by the expression of α-smooth muscle actin, calponin, and caldesmon, all of which are specific for the contractile phenotype [ 4 , 11 ].…”

“…The transformation of VSMCs from a contractile to a synthetic phenotype is a naturally occurring event during development and during vascular repair at sites of injury caused by, for example, hypertension, atherogenesis, and restenosis [ 4 , 8 , 11 , 12 ]. In atherosclerosis, VSMC phenotypic switching has a role in the initiation, stability, and, subsequently, the transfer of plaques [ 12 , 13 ].…”

Aortic regurgitation provokes phenotypic modulation of smooth muscle cells in the normal ascending aorta

“…To this point, the underlying mechanisms have not been investigated. SMCs in the aortic media regulate the turnover of elastin and ECM proteins 24 . Thus, these degenerative findings raise the question of whether SMC-mediated changes drive degeneration in the ascending aortic wall in individuals with AR.…”