Fig. 2

The pathogenic effects of upregulated atherogenic mechanosensory miRNAs. In conditions of high sheer stress, mechanosensitive miRNAs play a major role in maintaining the function and integrity of the vascular epithelium. However, in an environment of chronic inflammation and oxidative stress, the consequent upregulation of atherogenic miRNAs such as miRNA-92 induces EC dysfunction and activation by inhibiting the activity of KLFs and, to a lesser extent, SOCS-1. The resultant upregulation of NF-κB and SOCS-1 increases the internal production of PICs, MCP-1 and IL-6 and stimulates the increased expression of adhesion factors and chemokines on the EC surface. The resultant release of cytokines into the environment increases the inflammatory milieu and may establish a self-amplifying environment of inflammation and oxidative stress with the ECs and beyond