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Cited by 17Trauma, Hemostasis, Coagulopathy, ResuscitationRespiratory Support and MechanismsAngiogenesis and VEGF in Cancer

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Effects of trauma, hemorrhagic shock, and chronic stress on lung vascular endothelial growth factor

Open access
Loftus, Tyler J., Thomson, Andrew J., Kannan, Kolenkode B., Alamo, Ines G., Ramos, Harry N., Whitley, Elizabeth E., Efron, Philip A., Mohr, Alicia M.·2017·Journal of Surgical Research
DOI 10.1016/j.jss.2016.10.023PMC PMC5412593
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Abstract

Background Vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1 and VEGFR-2) regulate vascular permeability and endothelial cell survival. We hypothesized that hemorrhagic shock (HS) and chronic stress (CS) would increase expression of lung VEGF and its receptors, potentiating pulmonary edema in lung tissue. Materials and methods Male Sprague-Dawley rats aged 8-9 wk were randomized: naïve control, lung contusion (LC), LC followed by HS (LCHS), and LCHS with CS in a restraint cylinder for 2 h/d (LCHS/CS). Animals were sacrificed on days 1 and 7. Expressions of lung VEGF, VEGFR-1, and VEGFR-2 were determined by polymerase chain reaction. Lung Injury Score (LIS) was graded on light microscopy by inflammatory cell counts, interstitial edema, pulmonary edema, and alveolar integrity (range: 0 = normal; 8 = severe injury). Results Seven days after LC, lung VEGF and VEGFR-1 were increased, and lung tissue healed (LIS: 0.8 ± 0.8). However, 7 d after LCHS and LCHS/CS, lung VEGF and VEGFR-1 expressions were decreased. VEGFR-2 was also decreased after LCHS/CS. LIS was elevated 7 d after LCHS and LCHS/CS (6.5 ± 1.0 and 8.2 ± 0.8). Increased LIS after LCHS and LCHS/CS was because of higher inflammatory cell counts, increased interstitial edema, and loss of alveolar integrity, whereas pulmonary edema was unchanged. Conclusions Elevation of lung VEGF and VEGFR-1 expressions after LC alone was associated with healing of injured lung tissue. Expressions of VEGF, VEGFR-1, and VEGFR-2 were reduced after LCHS and LCHS/CS, and injured lung tissue did not heal. Persistent lung injury after severe trauma was because of inflammation rather than pulmonary edema.

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  • In trauma, serum albumin concentration decreases, vascular permeability increases, absolute synthesis increases, half-life decreases, distribution volume increases, and VEGF increases.

    “Trauma | ↓ to ↓↓ | ↑ to↑↑ | ↑ to↑↑ | ↓ to ↓↓ | NA | ↑ to↑↑ | ↑36 | Data in part from4”

    From Hypoalbuminemia: Pathogenesis and Clinical Significance (2019) · cites this paper as [36]

    The citation appears attached to the VEGF increase, rather than to the albumin-related columns. The Results (Day 1 and day 7: VEGF, VEGFR-1, and VEGFR-2; page unavailable) report increased lung VEGF seven days after lung contusion alone, but decreased lung VEGF after contusion with hemorrhagic shock, with or without chronic stress. VEGF was undetectable in plasma in every group, so the source does not support an unqualified increase in VEGF after trauma. (LLM, conf=0.89)

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  • VEGF expression and increased vascular permeability occur in infection, trauma, during fetal and postnatal growth, preparing for lactation, cancer, protein-losing enteropathy, and nephrotic syndrome.

    “VEGF expression and increased vascular permeability occur in infection,14, 35 trauma,15, 16, 36 during fetal and postnatal growth,29, 37, 38, 39 preparing for lactation,39, 40 cancer,41, 42 protein‐losing enteropathy,43 and nephrotic syndrome44, 45 (Table 1).”

    From Hypoalbuminemia: Pathogenesis and Clinical Significance (2019) · cites this paper as [36]

    The Results (page unavailable) report increased lung VEGF expression seven days after lung contusion alone, supporting the trauma portion of the citing sentence. The Introduction says VEGF promotes vascular permeability, but the study does not show increased permeability after trauma; its Results report unchanged pulmonary edema and decreased VEGF expression when contusion was combined with hemorrhagic shock. (LLM, conf=0.86)

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Citations

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Research works printed but not linked: 29

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Metadata

Authors
Loftus, T. J., Thomson, A. J., Kannan, K. B., Alamo, I. G., Ramos, H. N., Whitley, E. E., Efron, P. A., & Mohr, A. M.
Affiliations
University of Florida Health (US)
Corresponding author
Mohr, Alicia M.
ORCID
Venue
Journal of Surgical Research
Publisher
Elsevier BV
Published
2017-04
Volume
210
Pages
15-21
ISSN
0022-4804 (ISSN-L)
DOI
10.1016/j.jss.2016.10.023
PMC
PMC5412593
OpenAlex
W2548617769
Cited by
17
References
1
Citations by year
2026: 3 · 2025: 1 · 2024: 2 · 2023: 2 · 2021: 2 · 2020: 2 · 2018: 2 · 2017: 2
FWCI
1.21
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Surgical Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (P30 AG028740)
  • National Institute of General Medical Sciences (R01 GM113945-01, R01 GM105893-01A1, P50 GM111152–01)
Topics
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
vascular endothelial growth factor, VEGFR1, VEGFR2, hemorrhagic shock, chronic stress, pulmonary contusion, pulmonary edema, lung injury, inflammation, interstitial edema, trauma (physical injury)
MeSH terms
Animals, Chronic Disease, Male, Pulmonary Edema, Random Allocation, Shock, Hemorrhagic, Stress, Psychological, Biomarkers, Rats, Sprague-Dawley, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor Receptor-2, Vascular Endothelial Growth Factor A, Rats, Lung Injury

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