Vascular Endothelial Growth Factor-121 Administration Mitigates Halogen Inhalation-Induced Pulmonary Injury and Fetal Growth Restriction in Pregnant Mice

被引:16
作者
Addis, Dylan R. [1 ,2 ,3 ,6 ]
Lambert, James A. [2 ,4 ,6 ]
Ren, Changchun [5 ,6 ]
Doran, Stephen [2 ,6 ]
Aggarwal, Saurabh [2 ,6 ]
Jilling, Tamas [5 ,6 ]
Matalon, Sadis [2 ,3 ,6 ]
机构
[1] Dept Anesthesiol & Perioperat Med, Div Cardiothorac Anesthesiol, Birmingham, AL USA
[2] Dept Anesthesiol & Perioperat Med, Div Mol & Translat Biomed, Birmingham, AL USA
[3] UAB Comprehens Cardiovasc Ctr Univ Alabama Birmin, Birmingham, AL USA
[4] Grad Biomed Sci Biochem Struct & Stem Cell Biol T, Birmingham, AL USA
[5] Dept Pediat, Div Neonatol, Birmingham, AL USA
[6] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA
来源
JOURNAL OF THE AMERICAN HEART ASSOCIATION | 2020年 / 9卷 / 03期
基金
美国国家卫生研究院;
关键词
hemodynamics; lung edema; preeclampsia; pregnancy; vascular biology; SOLUBLE VEGF RECEPTOR-1; PLACENTAL ISCHEMIA; BROMINE EXPOSURE; MOUSE MODEL; CHLORINE; PREECLAMPSIA; HYPERTENSION; GRANITEVILLE; PRAVASTATIN; SURFACTANT;
D O I
10.1161/JAHA.119.013238
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Circulating levels of sFLT-1 (soluble fms-like tyrosine kinase 1), the extracellular domain of vascular endothelial growth factor (VEGF) receptor 1, and its ratio to levels of placental growth factor are markers of the occurrence and severity of preeclampsia. Methods and Results C57BL/6 pregnant mice on embryonic day 14.5 (E14.5), male, and non-pregnant female mice were exposed to air or to Br-2 at 600 ppm for 30 minutes and were treated with vehicle or with VEGF-121 (100 mu g/kg, subcutaneously) daily, starting 48 hours post-exposure. Plasma, bronchoalveolar lavage fluid, lungs, fetuses, and placentas were collected 120 hours post-exposure. In Br-2-exposed pregnant mice, there was a time-dependent and significant increase in plasma levels of sFLT-1 which correlated with increases in mouse lung wet/dry weights and bronchoalveolar lavage fluid protein content. Supplementation of exogenous VEGF-121 improved survival and weight gain, reduced lung wet/dry weights, decreased bronchoalveolar lavage fluid protein levels, enhanced placental development, and improved fetal growth in pregnant mice exposed to Br-2. Exogenous VEGF-121 administration had no effect in non-pregnant mice. Conclusions These results implicate inhibition of VEGF signaling driven by sFLT-1 overexpression as a mechanism of pregnancy-specific injury leading to lung edema, maternal mortality, and fetal growth restriction after bromine gas exposure.
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页数:12
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共 40 条
[11]   Formation of chlorinated lipids post-chlorine gas exposure [J].
Ford, David A. ;
Honavar, Jaideep ;
Albert, Carolyn J. ;
Duerr, Mark A. ;
Oh, Joo Yeun ;
Doran, Stephen ;
Matalon, Sadis ;
Patel, Rakesh P. .
JOURNAL OF LIPID RESEARCH, 2016, 57 (08) :1529-1540
[12]   VEGF controls endothelial-cell permeability by promoting the β-arrestin-dependent endocytosis of VE-cadherin [J].
Gavard, Julie ;
Gutkind, J. Silvio .
NATURE CELL BIOLOGY, 2006, 8 (11) :1223-U17
[13]   Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction [J].
Gilbert, Jeffrey S. ;
Ryan, Michael J. ;
LaMarca, Babbette B. ;
Sedeek, Mona ;
Murphy, Sydney R. ;
Granger, Joey P. .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2008, 294 (02) :H541-H550
[14]   Recombinant Vascular Endothelial Growth Factor 121 Infusion Lowers Blood Pressure and Improves Renal Function in Rats With Placental Ischemia-Induced Hypertension [J].
Gilbert, Jeffrey S. ;
Verzwyvelt, Joseph ;
Colson, Drew ;
Arany, Marietta ;
Karumanchi, S. Ananth ;
Granger, Joey P. .
HYPERTENSION, 2010, 55 (02) :380-385
[15]   Surfactant alteration and replacement in acute respiratory distress syndrome [J].
Günther, A ;
Ruppert, C ;
Schmidt, R ;
Markart, P ;
Grimminger, F ;
Walmrath, D ;
Seeger, W .
RESPIRATORY RESEARCH, 2001, 2 (06) :353-U2
[16]   Surfactant in respiratory distress syndrome and lung injury [J].
Hallman, M ;
Glumoff, V ;
Rämet, M .
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR AND INTEGRATIVE PHYSIOLOGY, 2001, 129 (01) :287-294
[17]   Modeling an irritant gas plume for epidemiologic study [J].
Jani, Dev D. ;
Reed, David ;
Feigley, Charles E. ;
Svendsen, Erik R. .
INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH, 2016, 26 (01) :58-74
[18]   Compartmentalization of vascular endothelial growth factor to the epithelial surface of the human lung [J].
Kaner, RJ ;
Crystal, RG .
MOLECULAR MEDICINE, 2001, 7 (04) :240-246
[19]   Longitudinal changes in maternal serum placental growth factor and soluble fms-like tyrosine kinase-1 in women at increased risk of pre-eclampsia [J].
Khalil, A. ;
Maiz, N. ;
Garcia-Mandujano, R. ;
Penco, J. M. ;
Nicolaides, K. H. .
ULTRASOUND IN OBSTETRICS & GYNECOLOGY, 2016, 47 (03) :324-331
[20]   Placenta Growth Factor Induces Invasion and Activates p70 during Rapamycin Treatment in Trophoblast Cells [J].
Knuth, Allison ;
Liu, Lawrence ;
Nielsen, Halden ;
Merril, Daniel ;
Torry, Donald S. ;
Arroyo, Juan A. .
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 2015, 73 (04) :330-340