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The Phenotypic Responses of Vascular Smooth Muscle Cells Exposed to Mechanical Cues

Journal

CELLS
Volume 10, Issue 9, Pages -

Publisher

MDPI
DOI: 10.3390/cells10092209

Keywords

smooth muscle cells; mechanical forces; cyclic stretch; stiffness; extracellular matrix; phenotypic modulation

Categories

Funding

  1. Danish Ministry of Food, Agriculture and Fisheries (3R-Center Research Grant) [33010-NIFA-20-742]
  2. Aarhus University Research Foundation [AUFF-E-2019-7-23]

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During the development and culture of vascular smooth muscle cells (SMCs), a shift in cell phenotype occurs due to the absence of physiological signals. Most studies have been conducted under standard culture conditions, neglecting the impact of ECM microenvironment and mechanical forces on SMCs.
During the development of atherosclerosis and other vascular diseases, vascular smooth muscle cells (SMCs) located in the intima and media of blood vessels shift from a contractile state towards other phenotypes that differ substantially from differentiated SMCs. In addition, these cells acquire new functions, such as the production of alternative extracellular matrix (ECM) proteins and signal molecules. A similar shift in cell phenotype is observed when SMCs are removed from their native environment and placed in a culture, presumably due to the absence of the physiological signals that maintain and regulate the SMC phenotype in the vasculature. The far majority of studies describing SMC functions have been performed under standard culture conditions in which cells adhere to a rigid and static plastic plate. While these studies have contributed to discovering key molecular pathways regulating SMCs, they have a significant limitation: the ECM microenvironment and the mechanical forces transmitted through the matrix to SMCs are generally not considered. Here, we review and discuss the recent literature on how the mechanical forces and derived biochemical signals have been shown to modulate the vascular SMC phenotype and provide new perspectives about their importance.

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