Acinar-derived VEGF-A orchestrates blood vascular remodeling and preserves microvessels during acute pancreatitis.

Acute pancreatitis is a common inflammatory condition of the pancreas that can lead to severe complications such as chronic pancreatitis and pancreatic ductal adenocarcinoma. While vascular remodeling is a hallmark of many inflammatory conditions, the molecular mechanisms underlying vascular changes during pancreatitis remain largely unexplored. This study aimed to investigate the vascular changes associated with acute pancreatitis and to identify the molecular mechanisms underlying these changes. Acute pancreatitis was induced in wild-type mice through caerulein injections and resulted in progressive and substantial vascular changes, characterized by morphological remodeling, increased vessel density, and elevated vascular permeability. These structural changes were accompanied by molecular alterations, including increased expression of endothelial genes and decreased surface expression of vascular endothelial VE-cadherin. Injured acinar cells exhibited a significant increase in VEGF-A expression during pancreatitis. Acinar-specific VEGF-A inactivation led to marked impairments in vascular remodeling, with reduced vessel density and diminished number of vessels, without affecting immune cell infiltration, fibrosis, or acinar-to-ductal metaplasia. Together, our work identifies a mechanism by which increased expression of VEGF-A by acinar cells during pancreatitis is essential for maintaining vascular integrity and for driving vascular remodeling in the inflamed pancreas.