Intracavernous Injection of Mechanically Extracted Stromal Vascular Fragments Suppresses Endothelial‐Mesenchymal Transformation to Mitigate Erectile Dysfunction in Hypertensive Rats

Erectile dysfunction (ED) is widespread among individuals with high blood pressure and negatively affects quality of life. The effect of stromal vascular fraction (SVF) on hypertension‐related ED remains unexplored. We used a hypertensive rat model to explore the relative efficacy of adipose tissue stromal vascular fraction (tSVF) and cellular SVF (cSVF). We then investigated the possible mechanisms of these treatments. Hypertensive rats were divided into three groups according to different treatments. Their intracavernous pressure (ICP) during erection and condition of cavernous tissue were compared to those of the controlled group. Endothelial‐mesenchymal transformation (EndMT) markers as well as related inflammatory factors were also measured. cSVF and tSVF were labeled with CM‐Dil before injection in order to determine whether cSVF and tSVF survived, proliferated, and transdifferentiated in vivo. The increased ICP during erection demonstrated that tSVF treatment significantly improved hypertension‐related ED. tSVF increased the smooth muscle‐to‐collagen ratio and inhibiting the expression of fibrosis‐related proteins in hypertensive rats while rescuing the expression of vWF and eNOS, which indicated the preserving of endothelial tissue of the penis. Immunofluorescence staining and western blotting of penile tissue clearly suggest the inhibitory effect of tSVF on the overoccurring EndMT. Immunofluorescence staining and Western blot analysis of endothelial cells in vitro corroborate the whole‐tissue findings. The experiments in N‐nitro‐L‐arginine methyl ester hydrochloride (L‐NAME)–induced human umbilical vein endothelial cells (HUVECs) revealed tSVF suppresses EndMT via inhibiting the TGF‐ β 2–Smad2/Smad3 pathway. In vivo tSVF and cSVF tracing suggested that tSVF showed better longevity and transdifferentiation capacity than cSVF, thus exerting a more significant therapeutic effect. Treatment with tSVF significantly reserved erectile function in a hypertensive rat model. The mechanism appears to be inhibition of pathological EndMT through self‐differentiation. We conclude that tSVF is a promising therapeutic candidate for treating hypertensive ED.