A Prospective, Observational Study of Soluble FLT-1 and Vascular Endothelial Growth Factor in Sepsis

Abstract

Prior murine and human studies suggest that vascular endothelial growth factor (VEGF) contributes to endothelial cell activation and severity of illness in sepsis. Furthermore, circulating levels of soluble VEGF receptor 1 (sFLT) levels were found to increase as part of the early response to sepsis in mice. The objective of the study was to evaluate the blood levels of free VEGF-A and sFLT in patients presenting to the emergency department (ED) with suspected infection and to assess the relationship of these levels with severity of illness and inflammation. It was a prospective, observational study initiated in the ED of an urban, tertiary care, university hospital. Inclusion criteria were (1) ED patients aged 18 years or older and (2) clinical suspicion of infection. Eighty-three patients were enrolled in the study. The major findings were that (1) the mean VEGF and sFLT levels were increasingly higher across the following groups: noninfected control patients, infected patients without shock, and septic shock patients; (2) initial and 24-h VEGF levels had a significant correlation with the presence of septic shock at 24 h; (3) initial and 24-h sFLT levels correlated with Acute Physiology Age Chronic Health Evaluation II and Sepsis-related Organ/Failure Assessment scores initially and at 24 h; and (4) VEGF and sFLT levels correlated with inflammatory cascade activation. This is the first report of sFLT as a potential new marker of severity in patients with sepsis. Vascular endothelial cell growth factor and its signaling axis are important in the endothelial cell response to sepsis, and further elucidation of these mechanisms may lead to advances in future diagnostic and therapeutic opportunities.

Minimally invasive colon resection is associated with a transient increase in plasma sVEGFR1 levels and a decrease in sVEGFR2 levels during the early postoperative period

“…The weaknesses of this study include the limited number of late blood specimens and the bundling of samples. Of note, human and animal studies have shown that proinflammatory conditions such as pneumonia, adult respiratory distress syndrome (ARDS), and sepsis increase plasma levels of VEGF and sVEGFR1 [28][29][30][31][32]. MICR-related complications might also influence postoperative levels of sVEGFR1 and sVEGFR2.…”

The microcirculation as a diagnostic and therapeutic target in sepsis

“…VEGF causes endothelial permeability and proliferation, and may have pro-inflammatory effects by promoting adhesion of leukocytes to the endothelium. VEGF has recently been demonstrated to have an important role in the pathogenesis of sepsis, and increased levels of VEGF are related to a worsening organ dysfunction in septic patients [44]. Therefore, VEGF inhibition strategies may represent novel therapeutic targets in sepsis, whose downstream consequences may be achieved by improved microcirculatory flow.…”

Off-Pump CABG Surgery Reduces Systemic Inflammation Compared With On-Pump Surgery but Does Not Change Systemic Endothelial Responses

“…A soluble form of Flt-1 (sFlt-1) is shed from the endothelial membrane and acts as a decoy receptor that inhibits VEGF signaling. Both Ang/Tie2 system (14,19,20) and the VEGF/ VEGFR system (18,21,22) are involved in endothelial activation in organ failure (23). Several reports have been published about angiogenic and vascular leakageY related factors and their soluble receptors in patients with chronic heart failure (22), yet comprehensive data in patients undergoing on-pump versus off-pump CABG surgery are scarce.…”