LPS-Induced Vascular Endothelial Growth Factor Expression in Rat Lung Pericytes

Abstract

Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. Recent studies have shown that the VEGF levels increase in several cell types, for example, macrophages and smooth muscle cells after LPS stimulation, suggesting that it is important in the initiation and development of sepsis. In particular, LPS-regulated contractility in lung pericytes may play an important role in mediating pulmonary microvascular fluid hemodynamics during sepsis. This study investigated the production of VEGF by rat lung pericytes in response to LPS. LPS was found to enhance VEGF mRNA expression in a concentration-dependent manner peaking 2 h after stimulation in pericytes. Vascular endothelial growth factor protein levels in conditioned medium and in cell lysate also increased on increasing LPS and peaked after 24 to 48 h. LPS also significantly augmented iNOS expression in lung pericytes within 6 h. However, iNOS mRNA induction occurred later than LPS-induced VEGF mRNA increases. Interestingly, attempted inhibition with nuclear factor-kappaB or tyrosine kinase did not suppress LPS-induced augmented VEGF mRNA expression in lung pericytes, although both inhibitors markedly inhibited LPS-induced iNOS mRNA expression. SB203580, a p38 MAP kinase inhibitor, repressed LPS-induced VEGF mRNA expression. Furthermore, LPS stimulated a rapid and sustained phosphorylation of p38 MAP kinase. These results show that pericytes produce VEGF in response to LPS stimulation, and that this may be partly mediated by the p38 MAP kinase pathway. More research should be done to establish the regulation of capillary hemodynamics and identify mechanisms of their regulation.

Brain microvascular pericytes are immunoactive in culture: cytokine, chemokine, nitric oxide, and LRP-1 expression in response to lipopolysaccharide

“…Our results clearly showed that production of NO was blocked by pre-incubation of pericytes with these drugs. These results agree with those obtained from lung microvascular pericytes [29] and indicate that similar mechanisms are involved in activation of brain microvascular pericytes by LPS.…”

Cochlear Pericyte Responses to Acoustic Trauma and the Involvement of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor

“…46,47 Increased vascular permeability, induced by VEGF, is reported in different microvasculatures, including the lung. 48,49 Our data are consistent with those of Picciotti and colleagues 50 and Selivanova and colleagues, 51 who found that noise stimulation significantly increases VEGF expression in the stria vascularis. 50 …”

Biliary Infection May Exacerbate Biliary Cystogenesis Through the Induction of VEGF in Cholangiocytes of the Polycystic Kidney (PCK) Rat

“…In certain types of cells, LPS induces angiogenic factors, such as vascular endothelial growth factor (VEGF). 10,11 Because cholangiocytes express the receptor of LPS, Toll-like receptor 4 (TLR4), 12,13 LPS may also be able to induce angiogenic growth factors in cholangiocytes.…”