Hepatic Arterial Flow-Induced Portal Tract Fibrosis in Portal Hypertension: The Role of VCAM-1 and Osteopontin-Expressing Macrophages

BACKGROUND & AIMS: The liver undergoes significant hemodynamic changes during surgery, transplantation, or cirrhosis with portal hypertension (PH). The hepatic artery buffer response (HABR), which compensates for reduced portal venous flow by increasing hepatic artery (HA) flow, is hypothesized to induce pathological portal tract remodeling. This study investigates the molecular mechanisms underlying this process. METHODS: PH was induced in Sprague-Dawley rats via partial portal vein ligation (PPVL). Structural evaluation (micro computed tomography [microCT]), immune cell profiling, hemodynamic measurements, and transcriptomic analysis in macrophages from sham or PPVL rats were conducted. RESULTS: macrophages driving fibrosis. Spp1 knockdown in macrophages co-culture reduced PF fibrogenic markers, whereas recombinant SPP1 upregulated Col1a1, Fn1, and Acta2 expression in PFs. CONCLUSIONS: macrophages, which drive HA flow-mediated vascular remodeling and portal tract fibrosis. These findings highlight arterial flow-induced fibrosis as a key mechanism in PH, potentially contributing to disease progression and decompensation.