Characterization Of Circulating Fibrocytes In People Living With HIV
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2022
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University of Hawaii at Manoa
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Fibrosis is estimated to account for 45% of all-cause mortality in the developed world. Immune dysregulation and chronic inflammation are potent contributors to fibrotic disease, increasingly so in people living with HIV (PLWH), independent of viral suppression. Fibrocytes are bone marrow-derived fibroblast-like cells whose increased numbers have been correlated with incidence and severity of fibrotic diseases. Despite their relevance to fibrosis, studies characterizing the fibrocyte in PLWH are scarce. Using 34 HIV+ individuals on suppressive antiretroviral therapy and 34 healthy controls (HC) we identified and quantified circulating fibrocytes in peripheral blood mononuclear cell (PBMC) samples. Participants were similar in age with a median age of 59.96 (56-63) years in HIV+ and 59.23 (56-64) years in HC and both groups were 88.2% male. No significant difference in non-infectious comorbidity prevalence was noted between the groups. HIV+ participantsʻ median CD4 count was within normal limits at 747.5 (601-898) cells/μL. Fibrocyte and activated fibrocyte numbers were not different between HIV+ and HC (p=0.257 and p=0.866, respectively). Similarly, the percentage of fibrocytes and activated fibrocytes from total CD45+ cells did not significantly differ (p=0.235 and p=0.710, respectively). However, fibrocyte numbers and the percentage of fibrocytes from CD45+ cells were significantly associated with increasing age in both HIV+ and HC groups (r=0.558, p=<0.0001 and r=0.575, p=<0.0001, respectively). Cultured fibrocytes isolated from HIV+ PBMC exhibited an increasing trend of mRNA expression of collagen-1 (COL-1), α-smooth muscle actin (α-SMA), vimentin, CCR5, and CCR7 with a trend towards decreased mRNA expression of CXCR4 and CCR3 compared to HC fibrocytes. Cultured HIV+ and HC fibrocytes treated with TGF-β1 at 5ng/mL and 20ng/mL enhanced fold change expression in COL-1, α-SMA, and chemokine receptor genes. Interestingly, fibrocytes from HIV+ PBMC exhibited decreased susceptibility to TGF- β1-induced COL-1 and CCR7 expression compared to HC. Our study demonstrates that circulating fibrocyte and activated fibrocyte populations are comparable between and strongly associated with age in virally suppressed PLWH and HC. In addition, cultured fibrocytes from PLWH demonstrated different responses to TGF- β1 stimulation compared to HC.
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Fibroblasts, HIV-positive persons, Fibrosis, Aging
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