Osteopontin may be a driver of abdominal aortic aneurysm formation

S. Keisin Wang, Linden A. Green, Ashley R. Gutwein, Alok K. Gupta, Clifford M. Babbey, Raghu Motaganahalli, Andres Fajardo, Michael Murphy

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective: Previous in vitro and animal studies have suggested that osteopontin (OPN), an inflammatory extracellular matrix protein, is involved in the formation and growth of abdominal aortic aneurysms (AAAs). However, the mechanism by which this occurs continues to be nebulous. The relationship between OPN and inflammation-suppressing lymphocytes present in the human AAA condition was investigated and presented herein. Methods: Serum OPN concentrations were measured in healthy, risk factor-matched non-AAA and AAA patients by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to determine the source of OPN secretion using aortic tissue collected from multiorgan donors and AAA patients undergoing open surgical repair. Vascular smooth muscle cells (VSMCs) were exposed to various inflammatory mediators, and OPN expression was evaluated by quantitative reverse transcriptase-polymerase chain reaction and ELISA. The inflammatory nature of OPN and the aortic wall was determined using a TR1 suppressor cell induction assay as a surrogate and characterized by ELISA and fluorescence-activated cell sorting. Results: OPN was found to be elevated in both the plasma and aortic homogenate of AAA patients compared with controls. On immunohistochemistry, OPN localized to the tunica media of the diseased aorta but was minimally expressed in healthy aorta. In vitro, cigarette smoke extract was the most potent stimulator of OPN secretion by VSMCs and increased both messenger RNA and supernatant concentrations. OPN demonstrated an ability to inhibit the induction of interleukin 10-secreting TR1 lymphocytes, a depleted population in the AAA patient, from naive precursors. Last, neutralizing receptor targets of OPN in the setting of AAA homogenate coincubation abrogated the inhibition of TR1 induction. Conclusions: OPN, secreted by the VSMCs of the tunica media, is elevated in the circulating plasma and aortic wall of patients with AAA. It can inhibit the induction of the TR1 suppressor cell, leading to an overall proinflammatory state contributing to progressive aortic wall breakdown and dilation.

Original languageEnglish (US)
JournalJournal of Vascular Surgery
DOIs
StateAccepted/In press - Jan 1 2018

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Osteopontin
Abdominal Aortic Aneurysm
Vascular Smooth Muscle
Tunica Media
Smooth Muscle Myocytes
Enzyme-Linked Immunosorbent Assay
Aorta
Immunohistochemistry
Lymphocytes
Aortic Aneurysm
Extracellular Matrix Proteins
Reverse Transcriptase Polymerase Chain Reaction
Smoke
Tobacco Products
Interleukin-10
Dilatation
Flow Cytometry

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

Osteopontin may be a driver of abdominal aortic aneurysm formation. / Wang, S. Keisin; Green, Linden A.; Gutwein, Ashley R.; Gupta, Alok K.; Babbey, Clifford M.; Motaganahalli, Raghu; Fajardo, Andres; Murphy, Michael.

In: Journal of Vascular Surgery, 01.01.2018.

Research output: Contribution to journalArticle

Wang, S. Keisin ; Green, Linden A. ; Gutwein, Ashley R. ; Gupta, Alok K. ; Babbey, Clifford M. ; Motaganahalli, Raghu ; Fajardo, Andres ; Murphy, Michael. / Osteopontin may be a driver of abdominal aortic aneurysm formation. In: Journal of Vascular Surgery. 2018.
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abstract = "Objective: Previous in vitro and animal studies have suggested that osteopontin (OPN), an inflammatory extracellular matrix protein, is involved in the formation and growth of abdominal aortic aneurysms (AAAs). However, the mechanism by which this occurs continues to be nebulous. The relationship between OPN and inflammation-suppressing lymphocytes present in the human AAA condition was investigated and presented herein. Methods: Serum OPN concentrations were measured in healthy, risk factor-matched non-AAA and AAA patients by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to determine the source of OPN secretion using aortic tissue collected from multiorgan donors and AAA patients undergoing open surgical repair. Vascular smooth muscle cells (VSMCs) were exposed to various inflammatory mediators, and OPN expression was evaluated by quantitative reverse transcriptase-polymerase chain reaction and ELISA. The inflammatory nature of OPN and the aortic wall was determined using a TR1 suppressor cell induction assay as a surrogate and characterized by ELISA and fluorescence-activated cell sorting. Results: OPN was found to be elevated in both the plasma and aortic homogenate of AAA patients compared with controls. On immunohistochemistry, OPN localized to the tunica media of the diseased aorta but was minimally expressed in healthy aorta. In vitro, cigarette smoke extract was the most potent stimulator of OPN secretion by VSMCs and increased both messenger RNA and supernatant concentrations. OPN demonstrated an ability to inhibit the induction of interleukin 10-secreting TR1 lymphocytes, a depleted population in the AAA patient, from naive precursors. Last, neutralizing receptor targets of OPN in the setting of AAA homogenate coincubation abrogated the inhibition of TR1 induction. Conclusions: OPN, secreted by the VSMCs of the tunica media, is elevated in the circulating plasma and aortic wall of patients with AAA. It can inhibit the induction of the TR1 suppressor cell, leading to an overall proinflammatory state contributing to progressive aortic wall breakdown and dilation.",
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AU - Babbey, Clifford M.

AU - Motaganahalli, Raghu

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