Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Osteopontin is an integral mediator of cardiac interstitial fibrosis in models of HIV infection.


BACKGROUND: People with human immunodeficiency virus (HIV) (PWH) have heightened incidence/risk of diastolic dysfunction and heart failure. Women with HIV (WWH) have elevated cardiac fibrosis, and plasma osteopontin (Opn) correlated to cardiac pathology. Therefore, this study provides mechanistic insight into the relationship between osteopontin and cardiac fibrosis during HIV infection. METHODS: Mouse embryonic fibroblasts (MEFs) modeled cardiac fibroblasts in vitro. Simian immunodeficiency virus (SIV)-infected macaques with/without antiretroviral therapy (ART) and HIV-infected humanized mice modelled HIV-associated cardiac fibrosis. RESULTS: LPS-stimulated MEFs were myofibroblast-like, secreted cytokines, and produced Opn transcripts. SIV-infected animals had elevated plasma Opn at necropsy, full-length Opn in the ventricle, and ventricular interstitial fibrosis. Regression modelling identified growth differentiation factor (GDF)-15, CD14+CD16+ monocytes, and CD163 expression on CD14+ CD16+ monocytes as independent predictors of plasma Opn during SIV infection. HIV-infected humanized mice showed increased interstitial fibrosis compared to uninfected/untreated animals, and systemic inhibition of osteopontin by RNA aptamer reduced left ventricle fibrosis in HIV-infected humanized mice. DISCUSSION: Since Opn is elevated in the plasma and left ventricle during SIV infection and systemic inhibition of Opn reduced cardiac fibrosis in HIV-infected mice, Opn may be a potential target for adjunctive therapies to reduced cardiac fibrosis in PWH.

Authors: Robinson JA, Mahmud FJ, Greif E, Toribio M, Zanni MV, Brown AM, Burdo TH,
Journal: J Infect Dis . 2023 Jul 14;228(2):122-132. doi:10.1093/infdis/jiad149
Year: 2023
PubMed: PMID: 37162508 (Go to PubMed)