Based on these and other reports on the role of VEGF-A in LSEC fenestration and MASLD, it is likely that the ratio of VEGF-A and SEMA3A rather than one factor alone controls whether a liver remains fenestrated, attenuating hepatic steatosis or, alternatively, defenestrates, thus promoting early development of MASLD; however, from a pharmacologic point of view, blocking SEMA3A signaling may be more straightforward than activating a positive regulator such as VEGF-A and structural proteins that maintain fenestration23,74. This evidence concerns the gene VEGFA and metabolic dysfunction-associated steatotic liver disease.