Targeting the angiocrine with a selective ROCK2 inhibitor in liver fibrosis

Liver fibrosis, a hallmark of chronic liver diseases including metabolic dysfunction-associated steatohepatitis (MASH), remains a leading cause of global morbidity and mortality. Current therapies targeting metabolism or inflammation show limited efficacy against fibrosis and largely overlook the hepatic microvasculature. Blood vessels are not passive conduits but active signaling centers that secrete angiocrine factors. Here we identify ROCK2 as a key regulator of a pro-fibrotic angiocrine niche. The selective ROCK2 inhibitor TDI01 demonstrates potent anti-fibrotic effects in a minipig model and has shown favorable safety with trends of disease reversal in clinical trials, offering a novel “angiocrine” – based therapeutic strategy.