Figure 3.

An increase of VEGF contributes to an increase of endothelial cell stiffness at an instantaneous time period of minutes: left—a temporal increase of cell stiffness is exhibited to be a response to external force or shear stress in aortic endothelial cells [111]. Cellular stiffness quantified by the number of focal adhesions in endothelial cells (ECs) before (zero minutes) and after applying force (five minutes) is shown in simplified bars [111]. An increase of VEGF is reported to contribute to an increase of extracellular matrix stiffness of tumor endothelial cells in vitro [112]; right—vascular stiffness measured by pulse wave velocity (PWV) has been known to significantly increase in normal healthy individuals over aging [113], while VEGF levels, for example, in the brain decrease with increasing age at tissue level [2]. Illustration is modified from [114,115,116]. A question mark denotes the interpretation by present authors based on previous reports about changes in vascular stiffness at cellular level over a long period of aging [113,117] that needs a further clarification.