Variability in vascular smooth muscle cell stretch-induced responses in 2D culture

Laura-Eve Mantella, Adrian Quan, Subodh Verma

The pulsatile nature of blood flow exposes vascular smooth muscle cells (VSMCs) in the vessel wall to mechanical stress, in the form of circumferential and longitudinal stretch. Cyclic stretch evokes VSMC proliferation, apoptosis, phenotypic switching, migration, alignment, and vascular remodeling. Given that these responses have been observed in many cardiovascular diseases, a defined understanding of their underlying mechanisms may provide critical insight into the pathophysiology of cardiovascular derangements. Cyclic stretch-triggered VSMC responses and their effector mechanisms have been studied in vitro using tension systems that apply either uniaxial or equibiaxial stretch to cells grown on an elastomer-bottomed culture plate and ex vivo by stretching whole vein segments with small weights. This review will focus mainly on VSMC responses to the in vitro application of mechanical stress, outlining the inconsistencies in acquired data, and comparing them to in vivo or ex vivo findings. Major discrepancies in data have been seen in mechanical stress-induced proliferation, apoptosis, and phenotypic switching responses, depending on the stretch conditions. These discrepancies stem from variations in stretch conditions such as degree, axis, duration, and frequency of stretch, wave function, membrane coating, cell type, cell passage number, culture media content, and choice of in vitro model. Further knowledge into the variables that cause these incongruities will allow for improvement of the in vitro application of cyclic stretch.