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Effects of HIV‐1 on Endothelial Gene Expression
Author(s) -
Porter Kristi Michelle,
Detorio Mervi,
Schinazi Raymond F,
Sutliff Roy L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1209.23
Subject(s) - endothelial dysfunction , peripheral blood mononuclear cell , immunology , angiotensin ii , medicine , population , immune system , downregulation and upregulation , gene , biology , blood pressure , genetics , in vitro , environmental health
Recent data suggest that HIV‐infected persons are at a heightened risk of developing non‐infectious lung disorders. HIV‐related pulmonary hypertension (HIV‐PH), a disorder characterized by increased pulmonary vessel tone and vascular remodeling, is one such example. HIV‐PH is estimated to occur 2500 times more frequently than primary PH in the general population. HIV‐PH is also found to progress more rapidly than primary PH with no association between CD4+ count and disease severity. These observations suggest a correlation between HIV infection and HIV‐PH unrelated to immune dysfunction. However, the cause of HIV‐PH is unknown. We hypothesize that HIV infection plays a critical role in HIV‐PH development by upregulating genes that modulate vasoconstriction and remodeling. To test this hypothesis, we employed co‐cultures of human pulmonary artery endothelial cells (HPAEC) and/or PBMC, either alone or exposed to HIV‐1. Gene array results showed a marked upregulation in the gelatinase, matrix metalloproteinase‐2 (MMP2) in the HPAEC, PBMC and HIV‐1 group as compared to other groups. RT‐PCR confirmed these results and also showed increased expression of angiotensinogen and angiotensin converting enzyme, precursors of the potent vasoconstrictor, angiotensin II. Altogether, our data suggest that HIV‐1‐induced gene alterations may contribute to the increased risk of HIV‐1 patients to develop PH.