Soluble vascular endothelial growth factor receptor-1 protects mice in sepsis

Tsao, Po‐Nien; Chan, Feng-Tsan; Wei, Shu–Chen; Hsieh, Wu‐Shiun; Chou, Hung-Chieh; Su, Yi‐Ning; Chen, Chien-Yi; Hsu, Wen-Ming; Hsieh, Fon‐Jou; Hsu, Su-Ming

doi:10.1097/01.ccm.0000275273.56547.b8

Cited by 56 publications

(61 citation statements)

References 43 publications

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“…These characteristics make sFlt-1 function as a dominant-negative inhibitor against VEGF and PlGF. 17,22 Serum sFlt-1 has been reported to be an antiangiogenesis factor that can inhibit tumor growth and metastasis. 23 According to our results, the preoperative serum sFlt-1 was decreased in the serum of CRC patients, compared with the levels of the control group.…”

Section: Discussionmentioning

confidence: 99%

Preoperative Serum Placenta Growth Factor Level Is a Prognostic Biomarker in Colorectal Cancer

Wei

Liang

Tsao

et al. 2009

Diseases of the Colon &Amp; Rectum

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Section: Discussionmentioning

confidence: 99%

Preoperative Serum Placenta Growth Factor Level Is a Prognostic Biomarker in Colorectal Cancer

Wei

Liang

Tsao

et al. 2009

Diseases of the Colon &Amp; Rectum

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“…Large retrospective cohort studies have documented a 3-to 7-fold increased risk of developing cardiovascular disease in women with preeclampsia later in life [28]. This increased risk is based on genetic determinants shared with metabolic syndrome and inflammation [29].…”

Section: Insulin Resistance In Preeclampsia and Resultant Endothelialmentioning

confidence: 99%

Preeclampsia as a Form of Type 5 Cardiorenal Syndrome: An Underrecognized Entity in Women’s Cardiovascular Health

2018

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Background: Preeclampsia is a multisystem vascular disorder of pregnancy that remains a leading cause of maternal and fetal morbidity and mortality. Preeclampsia remains an underrecognized risk factor for future cardiovascular and kidney disease in women and represents the confluence of preexisting vascular risk factors with superimposed endothelial injury from placental mediated anti-angiogenic factors. Summary: This review highlights the close relationship between preeclampsia and future cardiovascular and kidney disease. It describes the pathophysiology and current understanding of biomarkers that form the molecular signature for long-term endothelial dysfunction in preeclamptic women. Finally, it describes strategies for early identification and management of women with preeclampsia with elevated risk for cardiovascular and kidney disease. Key Messages: Future rigorous studies on cardiovascular risk modification in this phenotype of disease are essential to reduce the burden of cardiovascular and kidney disease, in women with preeclampsia.

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“…In addition, Shapiro et al [9] showed that the circulatory soluble fms-like tyrosine kinase-1 receptor (sFlt-1) level was increased in septic patients and that the increase was correlated with disease severity. Furthermore, our group [11] and Yano et al [12] have demonstrated that treatment with exogenous sFlt-1 or adenovirus-mediated overexpression of sFlt-1 attenuates inflammatory response and decreases mortality in experimental sepsis through antagonization of LPS-induced VEGF secretion [11,12]. These findings indicate that increasing the plasma sFlt-1:VEGF ratio during sepsis may be an effective therapeutic adjuvant for treatment of septic shock as well as severe immune responses caused by microbe-mediated diseases.…”

Section: Introductionmentioning

confidence: 90%

Novel PKC signaling is required for LPS-induced soluble Flt-1 expression in macrophages

Lee

Wei

Tsai-Wu

et al. 2008

Journal of Leukocyte Biology

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In vitro activation of macrophages by LPS induces rapid release of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase-1 receptor (sFlt-1), which are thought to be the effectors to cause sepsis. However, the signal pathway that controls the VEGF and sFlt-1 expressions in LPS-activated macrophages remains unclear. In this study, we demonstrated that phosphorylation of protein kinase C (PKC)delta played a key role in the VEGF and sFlt-1 signaling pathway of LPS-activated macrophages. PKC is a family of serine-threonine kinases, which are classified into three major groups based on homology and cofactor requirements: conventional PKCs, novel PKCs, and atypical PKCs. In the murine RAW264.7 cells, as well as in primary human monocytes/macrophages, pretreatment with a general PKC inhibitor GF109203X or with a novel PKCdelta inhibitor rottlerin or overexpression of a kinase-inactive form of PKCdelta (K376R) eliminated LPS-induced sFlt-1 expression and augmented LPS-induced VEGF expression at the protein and the transcription levels. In contrast, Gö6976, an inhibitor for the conventional PKCs, or myristoylated PKCzeta pseudosubstrate peptide, an inhibitor for the atypical PKCs, failed to exert the same effects. These data suggest that PKCdelta signaling is involved in LPS-induced sFlt-1 expression and serves as a negative mediator in LPS-induced VEGF expression in macrophages. A novel strategy controlling the LPS-induced PKC pathways, especially the PKCdelta isoform, may be developed based on this study.

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Soluble vascular endothelial growth factor receptor-1 protects mice in sepsis

Abstract: These findings support a critical protective role of sFlt-1 in endotoxic shock and sepsis. sFlt-1 may therefore have utility as an adjunctive agent for the treatment of sepsis syndrome.

Cited by 56 publications

References 43 publications

Preoperative Serum Placenta Growth Factor Level Is a Prognostic Biomarker in Colorectal Cancer

Preoperative Serum Placenta Growth Factor Level Is a Prognostic Biomarker in Colorectal Cancer

Preeclampsia as a Form of Type 5 Cardiorenal Syndrome: An Underrecognized Entity in Women’s Cardiovascular Health

Novel PKC signaling is required for LPS-induced soluble Flt-1 expression in macrophages

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