SPP1 and aortic stenosis: On the other hand, genes downregulated in AS include (1) mediators protective in fibrosis, hypertrophy, or related inflammatory mechanisms (e.g., EREG50, PTX3 (fibroblast)51–53, HMOX1 (macrophage)54, OPN/SPP1 (neuronal)55, VSIG4 (cardiomyocyte, macrophage)56) or (2) those whose absence may benefit remodeling (e.g., IL1R1 (multiple cell types), where fibroblast-specific deletion limits post-infarct remodeling57; NPPC (fibroblast), whose deletion reduces fibrosis in diabetic cardiomyopathy58).