Present study aims at the effects of aerobic exercise on atherosclerosis. Aerobic exercise is the crucial prevention method in atherosclerosis which recommended from growing body of evidences, but few study demonstrated the effects of aerobic exercise on inflammatory response. SESNs are a highly conserved family proteins which induced by ER, DNA damage, inflammation and others. Jun Hee Lee et al also suggested SESNs is a feedback inhibitor of TOR that prevents age-related pathologies [25].
Level of SESN1 was up-regulated prominently after 8 weeks of aerobic exercise. The exciting result showed aerobic exercise is a vivo practical method to up-regulated SESN1 which contributed to alleviating inflammatory response. Our study disclose IL-1β/IL-6 and TNF-α are suppressed in aerobic exercise mice, and overexpression of SESN1 supposed to be the main reason according to our previous study [13]. Regarding to the potential mechanism: previous study reports that SESN1 as an activator of AMPK resulted in inhibiting mTORC1 [2, 26], mTORC1 enhanced the activation of NLRP3 inflammasome by various pathways [27, 28]. Other studies showed that AMPK modulated the inhibition of NLRP3 via mitochondrial biogenesis and the induction of autophagy [27]. Aerobic exercise activated the AMPK tend to inhibiting mTORC which eventually Inhibited the activation of NLRP3 inflammasome.
Another interesting consequence is MMP. MMP mainly resulted in plaque rupture which caused acute myocardial infarction. Despite present result showed MMP9/13 were both suppressed in aerobic exercise mice, but it still remained uncertain whether SESN1 participates the regulation of MMP since no evidence demonstrated the relationship between SESNs and MMP. The formation and structure of atherosclerotic plaque own some complex reasons such as infiltration and migration of monocytes, the expression of chemokines and the uptake of lipids. Further study need be performed in order to clarify the effects of SESN1 on the plaque.
Last intriguing finding of this study is that NF-κB signaling diminished in aerobic exercise mice, the underline mechanism due to the overexpression of SESN1 which caused by aerobic training. As far as we know, there is not exact evidence showing the regulatory role of SESN1 in NF-κB. However, SESN2 which belongs to the family proteins with SESN1, it had been proved that SESN2 positively regulated autophagy via binding to p62 or physically associating with ULK1 [13, 29]. Autophagy renders degradation of NIK and IKKs, leading to devitalization of NF-κB [30]. SESN1 may enhance autophagy in the same way as SESN2 did. Cardiovascular diseases are associated with oxidative stress strongly [31]. ROS are important biological molecules for maintaining homeostasis in the human body. Studies have proved excessive level of ROS accelerates the development of cardiovascular disorders by causing oxidative stress in the body [32]. Our previous study has revealed SESNs can be localized on the mitochondria and can control mitochondrial function via mTORC1-independent mechanisms, resulting in reduced production of ROS and cell death [7]. SESNs act as a peroxidase reductase, and SESN induction promotes the cyclic absorption of over-oxidized peroxidase, protecting cells from ROS accumulation [33].
Several limitations need be clarified. First of all, we performed 8 weeks of aerobic training without revealing a specific logical relationship between elevated protein levels and training duration. Second, as with training duration, the logical relationship between training intensity and protein expression levels was unclear. Third, the effect of aerobic training on foam cell formation, especially on lipid infiltration in the aorta, was not investigated in this study. Last, the regulatory effect of exercise on other SESNs subtypes has not been clarified in this study. In order to perfect therapeutic strategies of SESN1, above questions need be resolved. In addition to aerobic exercise, disclose the upstream and downstream pathways that underlie SESN1’s multi-beneficial effects are indispensable.