An emerging view on vascular fibrosis molecular mediators and relevant disorders: from bench to bed

Figures

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  Figure 1. Pattern of changes in vascular structural composition (left) and alternations in a pathological fibrosing state (right). The tissue structure of the vessel wall, including tunica intima, media, and adventitia. The appropriate contraction of VSMCS and the amount of ECM protein ensure the normal elastic function of the vessel under physiological conditions. As vascular fibrosis develops, it leads to endothelial dysfunction, ECM remodeling, and EndMT, leading to arteriosclerosis and thickening of the vessel wall ultimately.

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  Figure 2. Molecular pathways of RAAS and TGF-β interactively induced vascular fibrosis. RAAS contains a series of molecules that are orderly activated, including angiotensinogen, renin, ACE, angiotensin I and II, and aldosterone. Among them, Ang II and Aldo plays crucial role in promoting fibrosis, acting through AT-1R and MR respectively. As a consequence, vascular cells gain a pro-fibrotic phenotype that includes TGF-β secretion. TGF-β acts through the cell membrane, triggering several intracellular molecular pathways, among which Smad signaling was canonically known. TGF-β/Smad induces nuclear fibrotic gene expression, followed by ECM, as well as VSMC changes, including collagen overexpression, elastin reduction, collagen and fibronectin deposition, MMP activation (along with MMP/TIMP imbalance) and so on. Progressively, preceding alternations directly lead to vascular fibrosis.

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  Figure 3. Molecular and cellular factors in vascular fibrosis related diseases and potential interventions. Hypertension, atherosclerosis, Kawasaki disease, Takayasu's diseases, diabetes and parenchymal disorders are all linked to vascular fibrosis in certain degree and are generally elaborated in this part. In different color mark different aspects of disease related fibrosis process: For columns in light red list the fibrotic-related major cellular or biologic incidents that undergoes in pathogenesis. Brown is for the diverse molecules with arrows indicating their up/down-regulations during diseases. Yellow is for several inhibitive medicines or molecules that can reverse the fibrotic molecules or events. The process of pyroptosis, autophagy, EndMT are also shown concisely.