Rapid clearance of circulating haptoglobin from plasma during acute pulmonary embolism in rats results in HMOX1 up-regulation in peripheral blood leukocytes

J. Zagorski, M. R. Marchick, Jeffrey Kline

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19 Citations (Scopus)

Abstract

Background: Acute pulmonary embolism (PE) causes pulmonary hypertension (PH) via several mechanisms including pulmonary vasospasm. We hypothesize that PE with associated PH leads to alterations in plasma protein concentrations indicative of disease severity and prognosis. Objective: To identify plasma proteins altered in abundance by PE in rats. Methods: Plasma samples were obtained from rats at 2, 6 and 18 h after experimental PE produced with intrajugular injection of polystyrene beads at three different levels of severity (mild, moderate and severe). Total plasma protein was separated using two-dimensional sodium dodecylsulfate-polyacrylamide gel electrophoresis (2D SDS-PAGE) and candidate protein spots altered in expression by PE were identified by mass spectroscopy. Haptoglobin identity and amount was verified by western blot analysis. Results: The PE model produced a dose-dependent increase in right ventricular systolic pressure (RVSP) (mmHg) at 2 h: mild 39 ± 1.7, moderate 40 ± 1.8 and severe 51 ± 1.3 mmHg, coincident with significant increases in free plasma (hemoglobin). Combined 2D SDS-PAGE and Western blot analysis indicated time- and dose-dependant loss of plasma haptoglobin levels in response to acute PE. Haptoglobin (HP) was essentially absent from plasma within 2 h of severe PE. Clearance of HP from plasma was accompanied by increased expression of heme oxygenase-1 (hmox1) in peripheral blood leukocytes and in HMOX1 enzyme activity in the liver. Conclusions: PE that causes pulmonary hypertension is associated with haptoglobin depletion and up-regulation of HMOX1 enzyme.

Original languageEnglish (US)
Pages (from-to)389-396
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Volume8
Issue number2
DOIs
StatePublished - Feb 2010
Externally publishedYes

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Haptoglobins
Pulmonary Embolism
Leukocytes
Up-Regulation
Pulmonary Hypertension
Blood Proteins
Polyacrylamide Gel Electrophoresis
Electrophoresis, Gel, Two-Dimensional
Western Blotting
Heme Oxygenase-1
Polystyrenes
Ventricular Pressure
Enzymes
Mass Spectrometry
Hemoglobins
Sodium
Blood Pressure
Lung
Injections
Liver

Keywords

  • Heme oxygenase
  • Hypertension
  • Inflammation
  • Proteomics
  • Pulmonary embolism

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "Rapid clearance of circulating haptoglobin from plasma during acute pulmonary embolism in rats results in HMOX1 up-regulation in peripheral blood leukocytes",
abstract = "Background: Acute pulmonary embolism (PE) causes pulmonary hypertension (PH) via several mechanisms including pulmonary vasospasm. We hypothesize that PE with associated PH leads to alterations in plasma protein concentrations indicative of disease severity and prognosis. Objective: To identify plasma proteins altered in abundance by PE in rats. Methods: Plasma samples were obtained from rats at 2, 6 and 18 h after experimental PE produced with intrajugular injection of polystyrene beads at three different levels of severity (mild, moderate and severe). Total plasma protein was separated using two-dimensional sodium dodecylsulfate-polyacrylamide gel electrophoresis (2D SDS-PAGE) and candidate protein spots altered in expression by PE were identified by mass spectroscopy. Haptoglobin identity and amount was verified by western blot analysis. Results: The PE model produced a dose-dependent increase in right ventricular systolic pressure (RVSP) (mmHg) at 2 h: mild 39 ± 1.7, moderate 40 ± 1.8 and severe 51 ± 1.3 mmHg, coincident with significant increases in free plasma (hemoglobin). Combined 2D SDS-PAGE and Western blot analysis indicated time- and dose-dependant loss of plasma haptoglobin levels in response to acute PE. Haptoglobin (HP) was essentially absent from plasma within 2 h of severe PE. Clearance of HP from plasma was accompanied by increased expression of heme oxygenase-1 (hmox1) in peripheral blood leukocytes and in HMOX1 enzyme activity in the liver. Conclusions: PE that causes pulmonary hypertension is associated with haptoglobin depletion and up-regulation of HMOX1 enzyme.",
keywords = "Heme oxygenase, Hypertension, Inflammation, Proteomics, Pulmonary embolism",
author = "J. Zagorski and Marchick, {M. R.} and Jeffrey Kline",
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language = "English (US)",
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pages = "389--396",
journal = "Journal of Thrombosis and Haemostasis",
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T1 - Rapid clearance of circulating haptoglobin from plasma during acute pulmonary embolism in rats results in HMOX1 up-regulation in peripheral blood leukocytes

AU - Zagorski, J.

AU - Marchick, M. R.

AU - Kline, Jeffrey

PY - 2010/2

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N2 - Background: Acute pulmonary embolism (PE) causes pulmonary hypertension (PH) via several mechanisms including pulmonary vasospasm. We hypothesize that PE with associated PH leads to alterations in plasma protein concentrations indicative of disease severity and prognosis. Objective: To identify plasma proteins altered in abundance by PE in rats. Methods: Plasma samples were obtained from rats at 2, 6 and 18 h after experimental PE produced with intrajugular injection of polystyrene beads at three different levels of severity (mild, moderate and severe). Total plasma protein was separated using two-dimensional sodium dodecylsulfate-polyacrylamide gel electrophoresis (2D SDS-PAGE) and candidate protein spots altered in expression by PE were identified by mass spectroscopy. Haptoglobin identity and amount was verified by western blot analysis. Results: The PE model produced a dose-dependent increase in right ventricular systolic pressure (RVSP) (mmHg) at 2 h: mild 39 ± 1.7, moderate 40 ± 1.8 and severe 51 ± 1.3 mmHg, coincident with significant increases in free plasma (hemoglobin). Combined 2D SDS-PAGE and Western blot analysis indicated time- and dose-dependant loss of plasma haptoglobin levels in response to acute PE. Haptoglobin (HP) was essentially absent from plasma within 2 h of severe PE. Clearance of HP from plasma was accompanied by increased expression of heme oxygenase-1 (hmox1) in peripheral blood leukocytes and in HMOX1 enzyme activity in the liver. Conclusions: PE that causes pulmonary hypertension is associated with haptoglobin depletion and up-regulation of HMOX1 enzyme.

AB - Background: Acute pulmonary embolism (PE) causes pulmonary hypertension (PH) via several mechanisms including pulmonary vasospasm. We hypothesize that PE with associated PH leads to alterations in plasma protein concentrations indicative of disease severity and prognosis. Objective: To identify plasma proteins altered in abundance by PE in rats. Methods: Plasma samples were obtained from rats at 2, 6 and 18 h after experimental PE produced with intrajugular injection of polystyrene beads at three different levels of severity (mild, moderate and severe). Total plasma protein was separated using two-dimensional sodium dodecylsulfate-polyacrylamide gel electrophoresis (2D SDS-PAGE) and candidate protein spots altered in expression by PE were identified by mass spectroscopy. Haptoglobin identity and amount was verified by western blot analysis. Results: The PE model produced a dose-dependent increase in right ventricular systolic pressure (RVSP) (mmHg) at 2 h: mild 39 ± 1.7, moderate 40 ± 1.8 and severe 51 ± 1.3 mmHg, coincident with significant increases in free plasma (hemoglobin). Combined 2D SDS-PAGE and Western blot analysis indicated time- and dose-dependant loss of plasma haptoglobin levels in response to acute PE. Haptoglobin (HP) was essentially absent from plasma within 2 h of severe PE. Clearance of HP from plasma was accompanied by increased expression of heme oxygenase-1 (hmox1) in peripheral blood leukocytes and in HMOX1 enzyme activity in the liver. Conclusions: PE that causes pulmonary hypertension is associated with haptoglobin depletion and up-regulation of HMOX1 enzyme.

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