Interleukin-6 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension

Figure 2

Hypothetical mechanism leading to pulmonary vascular remodeling via overexpression of IL-6. IL-6 induced proliferation and antiapoptosis in vascular smooth muscle cells through upregulation of VEGF, and downregulation of BMPR2 and TGF𝛽R2. Upon IL-6 exposure, endothelial cells undergo apoptosis through repressed Tie2 signaling via downregulated Ang-1 expression in smooth muscle cells. Production of CX3CL1 results in recruitment of inflammatory cells, such as lymphocytes and monocytes, which produce enormous amount of IL-6, while vascular smooth muscle and endothelial cells also produce IL-6 upon stimulation with IL-6.