Trypanosoma cruzi infection induces proliferation of vascular smooth muscle cells

Ghada S. Hassan, Shankar Mukherjee, Fnu Nagajyothi, Louis M. Weiss, Stefka B. Petkova, Cecilia J. De Almeida, Huan Huang, Mahalia S. Desruisseaux, Boumediene Bouzahzah, Richard G. Pestell, Chris Albanese, George J. Christ, Michael P. Lisanti, Herbert B. Tanowitz

Research output: Contribution to journalArticle

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Abstract

Trypanosoma cruzi infection causes cardiomyopathy and vasculopathy. Previous studies have demonstrated that infection of human umbilical vein endothelial and smooth muscle cells resulted in activation of extracellular signal-regulated kinase (ERK). In the present study, smooth muscle cells were infected with trypomastigotes, and immunoblot analysis revealed an increase in the expression of cyclin D1 and proliferating cell nuclear antigen (PCNA), important mediators of smooth muscle cell proliferation. Interestingly, after infection, the expression of caveolin-1 was reduced in both human umbilical vein endothelial cells and smooth muscle cells. Immunoblot and immunohistochemical analyses of lysates of carotid arteries obtained from infected mice revealed increased expression of PCNA, cyclin D1, its substrate, phospho-Rb (Ser780), and phospho-ERK1/2. The expression of the cyclin-dependent kinase inhibitor p21Cip/Waf1, caveolin-1, and caveolin-3 was reduced in carotid arteries obtained from infected mice. There was an increase in the abundance of pre-pro-endothelin-1 mRNA in the carotid artery and aorta from infected mice. The ETA receptor was also elevated in infected arteries. ERK activates endothelin-1, which in turn exerts positive feedback activating ERK, and cyclin D1 is a downstream target of both endothelin-1 and ERK. There was significant incorporation of bromodeoxyuridine into smooth muscle cell DNA when treatment was with conditioned medium obtained from infected endothelial cells. Taken together, these data suggest that T. cruzi infection stimulates smooth muscle cell proliferation and is likely a result of the upregulation of the ERK-cyclin D1-endothelin-1 pathway.

Original languageEnglish (US)
Pages (from-to)152-159
Number of pages8
JournalInfection and Immunity
Volume74
Issue number1
DOIs
StatePublished - Jan 2006

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Trypanosoma cruzi
Vascular Smooth Muscle
Extracellular Signal-Regulated MAP Kinases
Smooth Muscle Myocytes
Cyclin D1
Endothelin-1
Infection
Carotid Arteries
Caveolin 1
Proliferating Cell Nuclear Antigen
Caveolin 3
Cell Proliferation
Umbilical Veins
Cyclin-Dependent Kinases
Human Umbilical Vein Endothelial Cells
Bromodeoxyuridine
Conditioned Culture Medium
Cardiomyopathies
Aorta
Up-Regulation

ASJC Scopus subject areas

  • Immunology

Cite this

Hassan, G. S., Mukherjee, S., Nagajyothi, F., Weiss, L. M., Petkova, S. B., De Almeida, C. J., ... Tanowitz, H. B. (2006). Trypanosoma cruzi infection induces proliferation of vascular smooth muscle cells. Infection and Immunity, 74(1), 152-159. https://doi.org/10.1128/IAI.74.1.152-159.2006

Trypanosoma cruzi infection induces proliferation of vascular smooth muscle cells. / Hassan, Ghada S.; Mukherjee, Shankar; Nagajyothi, Fnu; Weiss, Louis M.; Petkova, Stefka B.; De Almeida, Cecilia J.; Huang, Huan; Desruisseaux, Mahalia S.; Bouzahzah, Boumediene; Pestell, Richard G.; Albanese, Chris; Christ, George J.; Lisanti, Michael P.; Tanowitz, Herbert B.

In: Infection and Immunity, Vol. 74, No. 1, 01.2006, p. 152-159.

Research output: Contribution to journalArticle

Hassan, GS, Mukherjee, S, Nagajyothi, F, Weiss, LM, Petkova, SB, De Almeida, CJ, Huang, H, Desruisseaux, MS, Bouzahzah, B, Pestell, RG, Albanese, C, Christ, GJ, Lisanti, MP & Tanowitz, HB 2006, 'Trypanosoma cruzi infection induces proliferation of vascular smooth muscle cells', Infection and Immunity, vol. 74, no. 1, pp. 152-159. https://doi.org/10.1128/IAI.74.1.152-159.2006
Hassan, Ghada S. ; Mukherjee, Shankar ; Nagajyothi, Fnu ; Weiss, Louis M. ; Petkova, Stefka B. ; De Almeida, Cecilia J. ; Huang, Huan ; Desruisseaux, Mahalia S. ; Bouzahzah, Boumediene ; Pestell, Richard G. ; Albanese, Chris ; Christ, George J. ; Lisanti, Michael P. ; Tanowitz, Herbert B. / Trypanosoma cruzi infection induces proliferation of vascular smooth muscle cells. In: Infection and Immunity. 2006 ; Vol. 74, No. 1. pp. 152-159.
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