Human immunodeficiency virus (HIV) infects human arterial smooth muscle cells in vivo and in vitro: Implications for the pathogenesis of HIV-mediated vascular disease

Eliseo Eugenin, Susan Morgello, Mary E. Klotman, Arevik Mosoian, Patrick A. Lento, Joan W. Berman, Alison D. Schecter

Research output: Contribution to journalArticle

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Abstract

Human immunodeficiency virus (HIV) infection is associated with accelerated atherosclerosis and vasculopathy, although the mechanisms underlying these findings have not been determined. Hypotheses for these observations include: 1) an increase in the prevalence of established cardiac risk factors observed in HIV-infected individuals who are currently experiencing longer life expectancies; 2) the dyslipidemia reported with certain HIV anti-retroviral therapies; and/or 3) the proinflammatory effects of infiltrating HIV-infected monocytes/macrophages. An unexplored possibility is whether HIV itself can infect vascular smooth muscle cells (SMCs) and, by doing so, whether SMCs can accelerate vascular disease. Our studies demonstrate that human SMCs can be infected with HIV both in vivo and in vitro. The HIV protein p24 was detected by fluorescence confocal microscopy in SMCs from tissue sections of human atherosclerotic plaques obtained from HIV-infected individuals. Human SMCs could also be infected in vitro with HIV by a mechanism dependent on CD4, the chemokine receptors CXCR4 or CCR5, and endocytosis, resulting in a marked increase in SMC secretion of the chemokine CCL2/MCP-1, which has been previously shown to be a critical mediator of atherosclerosis. In addition, SMC proliferation appeared concentric to the vessel lumen, and minimal inflammation was detected, unlike typical atherosclerosis. Our data suggest that direct infection of human arterial SMCs by HIV represents a potential mechanism in a multifactorial paradigm to explain the exacerbated atherosclerosis and vasculopathy reported in individuals infected with HIV.

Original languageEnglish (US)
Pages (from-to)1100-1111
Number of pages12
JournalAmerican Journal of Pathology
Volume172
Issue number4
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

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Vascular Diseases
Smooth Muscle Myocytes
HIV
Atherosclerosis
HIV Core Protein p24
In Vitro Techniques
CD4 Antigens
Chemokine CCL2
Chemokine Receptors
Virus Diseases
Atherosclerotic Plaques
Dyslipidemias
Life Expectancy
Endocytosis
Vascular Smooth Muscle
Fluorescence Microscopy
Confocal Microscopy
Monocytes
Macrophages
Cell Proliferation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Human immunodeficiency virus (HIV) infects human arterial smooth muscle cells in vivo and in vitro : Implications for the pathogenesis of HIV-mediated vascular disease. / Eugenin, Eliseo; Morgello, Susan; Klotman, Mary E.; Mosoian, Arevik; Lento, Patrick A.; Berman, Joan W.; Schecter, Alison D.

In: American Journal of Pathology, Vol. 172, No. 4, 01.01.2008, p. 1100-1111.

Research output: Contribution to journalArticle

Eugenin, Eliseo ; Morgello, Susan ; Klotman, Mary E. ; Mosoian, Arevik ; Lento, Patrick A. ; Berman, Joan W. ; Schecter, Alison D. / Human immunodeficiency virus (HIV) infects human arterial smooth muscle cells in vivo and in vitro : Implications for the pathogenesis of HIV-mediated vascular disease. In: American Journal of Pathology. 2008 ; Vol. 172, No. 4. pp. 1100-1111.
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