Ursolic acid, like reservatrol, increases Sirt-1 and restores the normal rate of autophagy from inhibition from oxidized LDL the toxic lipoprotein residue of foam cells and early atherosclerosis. Calcium and urate are the other toxic residues that increase NLRP3 and inhibits autophagy within atheromatous plaques.
Taken together Reservatrol and Ursolic acid increases (Sirt-1 and autophagy) and negates the effect of oxidized LDL or reduced calcium and urate thereby stabilizing or reversing unstable atheromatous plaques.
Though not stated, uric acid reduction should also have a similar effect.
Sirt-1 is a longevity gene. Autophagy and mitophagy are longevity processes. Of course, homeostasis is the goal and too little is the more common defect from inhibitors such as oxidized LDL, calcium and urate, over nutrition, under exercise. There are examples of too much autophagy such as in Charcot Marie tooth disorder.
Take home message is once again; Health plus autophagy,mitophagy minus inflamasome.
Resveratrol Enhances Autophagic Flux and Promotes Ox-LDL Degradation in HUVECs via Upregulation of SIRT1
Copyright © 2016 Yanlin Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Oxidized low-density lipoprotein- (Ox-LDL-) induced autophagy dysfunction in human vascular endothelial cells contributes to the development of atherosclerosis (AS). Resveratrol (RSV) protects against Ox-LDL-induced endothelium injury. The objective of this study was to determine the mechanisms underlying Ox-LDL-induced autophagy dysfunction and RSV-mediated protection in human umbilical vein endothelial cells (HUVECs). The results showed that Ox-LDL suppressed the expression of sirtuin 1 (SIRT1) and increased LC3-II and sequestosome 1 (p62) protein levels without altering p62 mRNA levels in HUVECs. Pretreatment with bafilomycin A1 (BafA1) to inhibit lysosomal degradation abrogated the Ox-LDL-induced increase in LC3-II protein level. Ox-LDL increased colocalization of GFP and RFP puncta in mRFP-GFP-tandem fluorescent LC3- (tf-LC3-) transfected cells. Moreover, Ox-LDL decreased the expression of mature cathepsin D and attenuated cathepsin D activity. Pretreatment with RSV increased the expression of SIRT1 and LC3-II and increased p62 protein degradation. RSV induced RFP-LC3 aggregation more than GFP-LC3 aggregation. RSV restored lysosomal function and promoted Ox-LDL degradation in HUVECs. All the protective effects of RSV were blocked after SIRT1 was knocked down. These findings demonstrated that RSV upregulated the expression of SIRT1, restored lysosomal function, enhanced Ox-LDL-induced impaired autophagic flux, and promoted Ox-LDL degradation through the autophagy-lysosome degradation pathway in HUVECs.
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