Therapeutic Effect of Cystatin on Atherosclerotic Renal Damage.

Atherosclerosis is a chronic inflammation of the arterial vessel wall driven by lipid metabolism disorders. Although helminthic infection and their derivatives have been identified to attenuate the chronic inflammatory diseases, the immunomodulatory effect of recombinant cystatin (r-Cys) on metabolic diseases and atherosclerosis has not been reported. In this study, we investigated the therapeutic efficacy of r-Cys on atherosclerotic renal damage and explored the related immunological mechanism. The results demonstrated that treatment with rCys significantly reduced body weight gain, hyperlipidemia, and atherosclerosis induced by the high-fat diet in apoE mice. The treatment of r-Cys also significantly improved kidney functions through promoting macrophage polarization from M1 to M2, therefore inhibiting M1 macrophage-induced inflammation. The possible mechanism underlying the regulatory effect of r-Cys on reducing atherosclerosis and atherosclerotic renal damage is that r-Cys stimulates regulatory T cell and M2 macrophage polarization that produce regulatory cytokines, such as interleukin 10 and transforming growth factor β. The therapeutic effect of r-Cys on atherosclerotic renal damage is possibly through inhibiting the activation of TLR2/Myd88 signaling pathway. The results in this study provide evidence for the first time that -derived cystatin could be developed as a therapeutic agent to treat lipid metabolism disorder and atherosclerosis that threats million lives around the world.