Angiotensin II aggravates lipopolysaccharide induced human pulmonary microvascular endothelial cells permeability in high glucose status.

Lung infection is one of the most common infections in diabetes mellitus and is characterized by increased pulmonary microvascular endothelial permeability. Local Angiotensin II (AngII) plays an important role in the pathogenesis of lung diseases. However, whether AngII can aggravate diabetic infectious lung injury is not clear. Therefore, we investigated the effects of AngII on the permeability of human pulmonary microvascular endothelial cells (HPMVECs) challenged by lipopolysaccharide (LPS) in high glucose states in vitro. HPMVECs were divided into five groups: a control group (CON), a high glucose group (HG), an LPS + high glucose group (LH), an LPS + high glucose + AngII group (LHA), and an LPS + high glucose + Losartan group (LHL). The HPMVECs permeability as well as the F-actin levels, cytoskeleton, apoptosis and TNF-α concentrations were evaluated. Compared to the CON group, the HG, LH and LHA groups had significantly higher cellular permeability, cellular apoptosis and TNF-α levels, with more extensive cytoskeletal damage and lower F-actin levels. Additionally, cells in the LHA group exhibited significantly elevated permeability, apoptosis and TNF-α concentrations, lower F-actin levels and more extensive cytoskeletal damage than either the LH or HG group. However, compared to the HG or LH group, the LHL group showed significantly lower cellular permeability, cell apoptosis, cytoskeletal damage and TNF-α concentrations and higher F-actin levels. This study suggests that in a diabetic infectious lung injury cellular model, AngII could aggravate the permeability of HPMVEC via F-actin dynamics and cell apoptosis. Furthermore, blocking the Angiotension II Type 1 Receptor could significantly alleviate the hyperpermeability of HPMVECs.