Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 234, Issue 5, Pages 5926-5939Publisher
WILEY
DOI: 10.1002/jcp.28003
Keywords
autophagy; cardiovascular disease; endothelial cells; NLRP3 inflammasome; senescence
Categories
Funding
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Natural Science Foundation by Jiangsu Normal University [11XLR21, 16XLR045]
- National Natural Science Foundation of China [81271225, 81400902, 81571055, 31201039, 81703523, 31200873, 81701821, 81570531]
- Special funds for promoting science and technology innovation in Xuzhou [KC16SG272]
- Natural Science Foundation of Jiangsu Province [BK2012143, BK20170244]
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Autophagy is a vital negative factor regulating cellular senescence. Purple sweet potato color (PSPC), one type of flavonoid, has been demonstrated to suppress endothelial senescence and restore endothelial function in diabetic mice by inhibiting the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome. However, the roles of autophagy in the inflammatory response during endothelial senescence are unknown. Here, we found that PSPC augmented autophagy to restrict high-glucose-induced premature endothelial senescence. In addition, PSPC administration impaired endothelium aging in diabetic mice by increasing autophagy. Inhibition of autophagy accelerated endothelial senescence, while enhancement of autophagy delayed senescence. Moreover, deactivation of the NLRP3 inflammasome triggered by PSPC was autophagy-dependent. Autophagy receptor microtubule-associated protein 1 light chain 3 and p62 interacted with the inflammasome component NLRP3, suggesting that autophagosomes target the NLRP3 inflammasome and deliver it to the lysosome for degradation. Altogether, PSPC amplified cellular autophagy, subsequently attenuated NLRP3 inflammasome activity and finally delayed endothelial senescence to ameliorate cardiovascular complication. These results suggest a potential therapeutic target in senescence-related cardiovascular diseases.
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