Multiscale Computational Modeling in Vascular Biology: From Molecular Mechanisms to Tissue-Level Structure and Function - Multiscale Computer Modeling in Biomechanics and Biomedical Engineering - page 210

Fig. 2 Illustrative arterial mechanics and molecular interactions. a The three layers of an artery
wall. The Intima is composed of endothelial cells and a basement membrane; the Media, smooth
muscle cells and primarily elastin and collagen; the Adventitia, fibroblasts and extracellular
matrix. Shear stress typically orients in the axial direction, while intramural stresses are
circumferential and axial in orientation. b Factors governed by shear stress and produced by
endothelial cells include NO, ET-1, and PDGF-AB. c Factors governed by circumferential stress
and produced by smooth muscle cells include PDGF-AB, TGF-b, and MMPs. Illustrative effects
of these growth factors and MMPs are shown to the right. PDGF-AB and TGF-b act through
complex intracellular pathways to promote collagen production and cell proliferation or

phenotypic switching, while MMPs degrade collagen, gelatin, and elastin

cells). That ECs respond directly to changing mechanical loads was first
noted *35 years ago and is now a well-documented example of mechanotrans-
duction—that is, the sensing and converting of mechanical stimuli into a signal
that controls gene expression and hence cellular activities. For example, ECs
increase their production of vasodilators (e.g., nitric oxide (NO) and prostacyclin
(PGI 2 )) in response to increases in wall shear stress; this allows the vessel to dilate,
thereby decreasing the resistance to flow, and promotes endothelial proliferation to
cover the increased surface area of the dilated vessel. Conversely, ECs increase
production of vasoconstrictors (e.g., endothelin-1 (ET-1) and angiotensin-II
(ANG-II)) in response to decreases in flow or increases in pressure. Endothelial
cells also produce a host of growth regulatory molecules (including vascular
endothelial growth factor (VEGF), platelet derived growth factors (PDGF),
fibroblast growth factors (FGF)), adhesion molecules (including vascular cell
adhesion molecule (VCAM-1) and intercellular adhesion molecule (ICAM-1)),