Abstract
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 Schistosoma japonicum cystatin (rSj-Cys) on metabolic diseases and atherosclerosis has not been reported. In this study, we investigated the therapeutic efficacy of rSj-Cys on atherosclerotic renal damage and explored the related immunological mechanism. The results demonstrated that treatment with rSj-Cys significantly reduced body weight gain, hyperlipidemia, and atherosclerosis induced by the high-fat diet in apoE–/– mice. The treatment of rSj-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 rSj-Cys on reducing atherosclerosis and atherosclerotic renal damage is that rSj-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 rSj-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 Schistosoma-derived cystatin could be developed as a therapeutic agent to treat lipid metabolism disorder and atherosclerosis that threats million lives around the world.
Highlights
Atherosclerosis is the chronic process of plaque buildup with deposition of fats, cholesterol, and other substances in and on artery walls, leading to the blood vessel hardened and narrowed and tissue ischemia (Li et al, 2015; Gistera and Hansson, 2017)
hematoxylin and eosin (HE) staining showed that the glomerular structure was damaged with inflammatory cell infiltration within renal interstitium in kidneys of mice fed with HFD for 12 weeks (Figure 3E)
There was no obvious oil red O– colored atherosclerotic lesions and renal tissue damage in groups of mice fed with normal control diet (NCD) and NCD/recombinant Schistosoma japonicum cystatin (rSj-Cys)
Summary
Atherosclerosis is the chronic process of plaque buildup with deposition of fats, cholesterol, and other substances in and on artery walls, leading to the blood vessel hardened and narrowed and tissue ischemia (Li et al, 2015; Gistera and Hansson, 2017) It causes a series of complications with life-threatening consequences, especially in the heart, brain, legs, arms, rSj-Cys Alleviates Atherosclerotic Renal Damage or kidneys. More evidence demonstrated that atherosclerosis is a lipid-driven chronic inflammatory disorder within the arterial wall characterized by the chronic activation of macrophages. Both innate and adaptive immunoinflammatory mechanisms are involved (Taleb, 2016; Geovanini and Libby, 2018). Disruption of TGF-β signaling in T cells exhibited markedly larger atherosclerotic lesions (Robertson et al, 2003)
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