Virus-encoded serine proteinase inhibitor SERP-1 inhibits atherosclerotic plaque development after balloon angioplasty

Alexandra Lucas, Li Ying Liu, Joanne Macen, Piers Nash, Erbin Dai, Michael Stewart, Kathryn Graham, Wai Etches, Lynn Boshkov, Patric N. Nation, Dennis Humen, Marita Lundstrom Hobman, Grant McFadden

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Background: Recurrent atherosclerotic plaque growth, restenosis, is a significant clinical problem after interventional procedures. Initiation of restenosis involves activation of inflammatory and thrombotic cascades, which are regulated by serine proteinase enzymes and inhibitors. We have investigated the use of a viral serine proteinase inhibitor, SERP-1, to reduce plaque development after primary balloon angioplasty. This is the first experimental report of the use of viral anti-inflammatory protein for the prevention of atherosclerosis. Methods and Results: Seventy-four cholesterol-fed rabbits were treated with either local or systemic infusions of SERP-1 protein (or control solutions) after balloon-mediated injury. Sites of SERP-1 infusion in rabbits had dramatically reduced plaque compared with control infusions at the 4-week follow-up. At low-dose infusion (30 to 300 pg), only the primary infusion site had a demonstrable decrease in plaque, whereas at higher-dose infusions (>3000 pg), a generalized reduction in plaque development was detected. An associated decrease in mononuclear cell infiltration of the arterial wall was detected after SERP-1 infusion within the first 24 hours. Infusion of an active-site mutant of SERP-1 (P1-P1', ala-ala) lacking serine proteinase inhibitory activity failed to prevent plaque growth. Conclusions: Purified SERP-1, a virus-encoded secreted glycoprotein, reduces plaque growth after primary balloon-mediated injury. Plaque development is decreased by inhibition of serine proteinase activity and is associated with a focal reduction in macrophage infiltration immediately after injury. Investigation of serine proteinase inhibitors may provide new insight into the regulation of arterial responses to injury.

Original languageEnglish (US)
Pages (from-to)2890-2900
Number of pages11
JournalCirculation
Volume94
Issue number11
StatePublished - 1996

Fingerprint

Serine Proteinase Inhibitors
Balloon Angioplasty
Atherosclerotic Plaques
Viruses
Wounds and Injuries
Serine Proteases
Growth
Rabbits
Enzyme Inhibitors
Catalytic Domain
Atherosclerosis
Glycoproteins
Proteins
Anti-Inflammatory Agents
Macrophages
Cholesterol

Keywords

  • angioplasty
  • immune system
  • plaque
  • serpin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Lucas, A., Liu, L. Y., Macen, J., Nash, P., Dai, E., Stewart, M., ... McFadden, G. (1996). Virus-encoded serine proteinase inhibitor SERP-1 inhibits atherosclerotic plaque development after balloon angioplasty. Circulation, 94(11), 2890-2900.

Virus-encoded serine proteinase inhibitor SERP-1 inhibits atherosclerotic plaque development after balloon angioplasty. / Lucas, Alexandra; Liu, Li Ying; Macen, Joanne; Nash, Piers; Dai, Erbin; Stewart, Michael; Graham, Kathryn; Etches, Wai; Boshkov, Lynn; Nation, Patric N.; Humen, Dennis; Hobman, Marita Lundstrom; McFadden, Grant.

In: Circulation, Vol. 94, No. 11, 1996, p. 2890-2900.

Research output: Contribution to journalArticle

Lucas, A, Liu, LY, Macen, J, Nash, P, Dai, E, Stewart, M, Graham, K, Etches, W, Boshkov, L, Nation, PN, Humen, D, Hobman, ML & McFadden, G 1996, 'Virus-encoded serine proteinase inhibitor SERP-1 inhibits atherosclerotic plaque development after balloon angioplasty', Circulation, vol. 94, no. 11, pp. 2890-2900.
Lucas, Alexandra ; Liu, Li Ying ; Macen, Joanne ; Nash, Piers ; Dai, Erbin ; Stewart, Michael ; Graham, Kathryn ; Etches, Wai ; Boshkov, Lynn ; Nation, Patric N. ; Humen, Dennis ; Hobman, Marita Lundstrom ; McFadden, Grant. / Virus-encoded serine proteinase inhibitor SERP-1 inhibits atherosclerotic plaque development after balloon angioplasty. In: Circulation. 1996 ; Vol. 94, No. 11. pp. 2890-2900.
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AU - Liu, Li Ying

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AU - Nash, Piers

AU - Dai, Erbin

AU - Stewart, Michael

AU - Graham, Kathryn

AU - Etches, Wai

AU - Boshkov, Lynn

AU - Nation, Patric N.

AU - Humen, Dennis

AU - Hobman, Marita Lundstrom

AU - McFadden, Grant

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