Plasma osteopontin relates to myocardial fibrosis and steatosis and to immune activation among women with HIV

Abstract

Objective:Women with HIV (WWH) have heightened heart failure risk. Plasma OPN (osteopontin) is a powerful predictor of heart failure outcomes in the general population. Limited data exist on relationships between plasma OPN and surrogates of HIV-associated heart failure risk.Design:Prospective, cross-sectional.Methods:We analyzed relationships between plasma OPN and cardiac structure/function (assessed using cardiovascular magnetic resonance imaging) and immune activation (biomarkers and flow cytometry) among 20 WWH and 14 women without HIV (WWOH).Results:Plasma OPN did not differ between groups. Among WWH, plasma OPN related directly to the markers of cardiac fibrosis, growth differentiation factor-15 (ρ = 0.51, P = 0.02) and soluble interleukin 1 receptor-like 1 (ρ = 0.45, P = 0.0459). Among WWH (but not among WWOH or the whole group), plasma OPN related directly to both myocardial fibrosis (ρ = 0.49, P = 0.03) and myocardial steatosis (ρ = 0.46, P = 0.0487). Among the whole group and WWH (and not among WWOH), plasma OPN related directly to the surface expression of C-X3-C motif chemokine receptor 1 (CX3CR1) on nonclassical (CD14−CD16+) monocytes (whole group: ρ = 0.36, P = 0.04; WWH: ρ = 0.46, P = 0.04). Further, among WWH and WWOH (and not among the whole group), plasma OPN related directly to the surface expression of CC motif chemokine receptor 2 (CCR2) on inflammatory (CD14+CD16+) monocytes (WWH: ρ = 0.54, P = 0.01; WWOH: ρ = 0.60, P = 0.03), and in WWH, this held even after controlling for HIV-specific parameters.Conclusion:Among WWH, plasma OPN, a powerful predictor of heart failure outcomes, related to myocardial fibrosis and steatosis and the expression of CCR2 and CX3CR1 on select monocyte subpopulations. OPN may play a role in heart failure pathogenesis among WWH.Clinicaltrials.gov Registration:NCT02874703.

HIV-Associated Cardiovascular Disease Pathogenesis: An Emerging Understanding Through Imaging and Immunology

“…They suggest that sST-2 in PLWH may be a mediator of the myocardial fibrosis extensively described in CMR studies. A direct link between myocardial fibrosis and inflammation was offered by 2 recent studies performed in women with HIV, demonstrating, respectively, a correlation between plasma osteopontin, a predictor of heart failure, myocardial fibrosis and the expression of 2 important chemokine receptors central to myocardial inflammation, CCR2 and CX3CR1 (C-X3-C motif chemokine receptor 1) in monocytes, 123 and a correlation between myocardial fibrosis, reduced diastolic function, and elevated systemic monocyte activation. 81 While our understanding of myocardial inflammation in HIV remains incomplete, the increased circulating levels of Gal-3 and sST-2 in PLWH highlight potential pathways through which HIV may contribute to myocardial fibrosis, suggesting new avenues for targeted therapeutic interventions and research.…”

Plasma osteopontin in persons with HIV and the risk for cardiovascular disease

“…However, as osteopontin is involved in a variety of physiological and pathophysiological conditions [4], the specificity to a condition like heart failure -in particular in a population without CVD -may be relatively low, limiting the clinical significance of findings. This is particularly relevant in the context of studying a large set of biomarkers and the associations between them in a relatively small group of women, as was done by Robinson and team, and reported in this issue and a related publication [20,27]. As with any study performing multiple comparisons, and in particular in research involving multiple biomarkers, it is important to take into account the risk of detecting spurious associations [28].…”

“…The study team found that plasma osteopontin was significantly associated with cardiac-MRI-derived intramyocardial triglyceride content and plasma growth differentiation factor 15 (GDF-15) -surrogate markers for myocardial steatosis and cardiac fibrosis, respectively. GDF-15 is a robust prognostic marker of and involved in myocardial pathophysiological processes underlying heart failure [19,20]. Both intramyocardial triglyceride content and GDF-15 are reported to be elevated and to be associated with preclinical markers of CVD in men and women with HIV [21][22][23].…”

“…Furthermore, in patients with chronic heart failure because of left ventricular function, levels correlate with the severity of heart failure and predict mortality [19]. By focusing on the potential role of osteopontin in the pathophysiology of heart failure in women with HIV (WWH), the study by Robinson et al [20] in this issue adds a layer of complexity. Little is known about the potential role of osteopontin in CVD among PWH.…”