Fig. 4. Elamipretide decreases senescence-associated β-galactosidase (SA-β-gal) activity in the stenotic kidneys (STKs). A. SA-β-Gal positive area (blue) increased both in the medulla and cortex of atherosclerotic renal artery stenosis (ARAS) STK, and decreased after elamipretide. B. P16-positive cells were increased in ARAS and tended to remain elevated in ARAS+elamipretide compared to normal pigs. Renal tubular (yellow arrowhead), interstitial (red arrowhead), and endothelial (red arrow) cells were p16-postivie in ARAS. C. In ARAS, the number of Ki67-positive cells (pink) per field was not different from normal, but increased in ARAS+elamipretide compared to in normal pigs. D. The numbers of senescence-associated heterochromatin-foci (SAHF)-positive cells (red) per field increased in ARAS and persisted in ARAS+elamipretide compared to normal. N, Normal; N+E, Normal+elamipretide; A, ARAS; A+E, ARAS+elamipretide. *P<0.05 vs. Normal, †P<0.05 vs. ARAS.