Editorial Volume 14, Issue 13 pp 5296—5298

Figure 1. Potential contributing mechanisms of SVF-induced reversal of aging-mediated βADR dysfunction. In aging, there is an overdrive of catecholamine production that facilitates βADR desensitization and internalization mediated by GRK2 (1). Transcription of catecholamine degradation enzyme COMT is significantly reduced by SVF therapy. There is no change in aging or SVF therapy in GRK2 transcription, however, naturally inhibited GRK2 (phosphorylated) is decreased in aging partially restored by SVF (albeit non-significantly) (2). Whether other post-translational modifications such as inhibitory nitric oxide-mediated S-nitrosylation of GRK2 contribute to SVF-mediated recovery of βADR function warrants investigation. The transcription of alpha arrestin 3 (arrdc3) was significantly enhanced in aging and reversed by SVF (3). Whether this contributes to coronary microvascular βADR dysfunction in aging, as it does in other vascular settings through βADR ubiquitination and delayed recycling, remains unknown. In other vascular settings, estrogen enhances βADR vasodilatory function and transcription via estrogen receptor-β, although there were no transcriptional differences between groups in our study (4). Transcription of estrogen receptor-α and Gper1 were significantly enhanced with SVF therapy, which may influence βADR transcription or enhance nitric oxide or attenuate ROS production as they are known to do in other vascular settings, which could influence βADR dilatory function (5). Yellow boxes represent gene expression whereas green boxes represent protein expression with red arrow indicating aging and blue arrow indicating SVF therapy. Question marks represent future directions to elucidate SVF-mediated recovery of βADR function based on RNA sequencing data. Image created with BioRender.com.