Circulating levels of transforming growth factor beta-1, 2 and 3 in HIV associated preeclamptic pregnancies

Abstract

The active role of transforming growth factor-beta in implantation, embryonic development and decidualization has driven our interest to evaluate circulating TGF-β(1–3) in the synergy of HIV associated pregnancy. Serum TGF-β(1–3) was quantified in normotensive (n = 38) and preeclamptic (n = 38) pregnant women, who were stratified by HIV status, HIV negative (n = 19) and HIV positive (n = 19), using a Bioplex immunoassay.

Based on HIV status, we report no significant difference in TGF-β-1 (p = .95) and TGF-β2 (p = .80) however, TGF-β3 was significantly downregulated in HIV positive (p = .03) vs the HIV negative groups. A significant positive correlation (p < .05) was noted between TGF-β3 and gestational age (p = .03) (r = 0.51), birth weight (p = .04) (r = 0.53) and CD4 count (p = .02) (r = 0.53). Bivariate correlation between isoforms based on HIV status showed several significant positive associations. In the synergy of HIV infected PE, we demonstrate an association between TGF-β(1–3) with PE emanating from the hypoxic microenvironment that affects receptor-SMAD activity. Decreased TGF-β3 levels in HIV infected PE, may originate from ARV usage and/or the mutational/physiological dysregulation of SMAD expression.

Impact Statement

• What is already known on this subject? TGF-β overexpression can convert its protective functions into pathogenic variants. It has a significant role in the oxidatively stressed and inflammatory condition of tissue fibrosis and hence may also be dysregulated in the microenvironment of PE. In HIV infection, TGF-β promotes viral replication and spreading through the induction of cellular proteins which induce TGF-β production. Also, mononuclear phagocytes infected with HIV also produce increased TGF-β mRNA and proteins.

• What do the results of the study add? Our results show no association of TGF-β isoforms (1–3) based on pregnancy type (PE vs normotensive pregnant) at term. The lack of association may be linked to TGF-βs dual promoter/suppresser nature or to gestational age.

• What are the implications of these findings for clinical practice and/or further research? Large-scale comprehensive clinical trials are warranted to elucidate the association and mechanistic role of TGF-β receptor-SMAD signalling, the effect of its inhibitors on cell invasion and angiogenesis as well as to deliver valuable data for the detection of novel therapeutic agents in pregnancies complicated by HIV infection.

Keywords:

• Preeclampsia
• HIV
• HAART
• TGF-β1
• TGF-β2
• TGF-β3

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

The work was supported by the College of Health Science, University of KwaZulu-Natal.