Interferon gamma-induced protein 10 (IP-10) and cardiovascular disease in African Americans

Leavitt, Colton; Zakai, Neil A.; Auer, Paul L.; Cushman, Mary; Lange, Ethan M.; Levitan, Emily B; Olson, Nels C.; Thornton, Timothy A.; Tracy, Russell P.; Wilson, James G.; Lange, Leslie A.; Reiner, Alex P.; Raffield, Laura M.

doi:10.1371/journal.pone.0231013

Cited by 17 publications

(11 citation statements)

References 62 publications

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“…Recently, it was demonstrated that CXCL10 is a circulating inflammatory marker in patients with advanced heart failure (Altara et al, 2016b ). Similarly, it is also reported that circulating levels of CXCL10 is associated with heart failure (Leavitt et al, 2020 ). These clinical findings demonstrate that blood concentration of CXCL10 is elevated in patients with heart failure; however, the mechanisms of CXCL10 induction remain to be addressed.…”

Section: Discussionmentioning

confidence: 81%

CXCL10 is a novel anti‐angiogenic factor downstream of p53 in cardiomyocytes

Wahyuni

Tanaka

Igarashi

et al. 2022

Physiological Reports

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Tumor suppressor protein p53 plays crucial roles in the onset of heart failure. p53 activation results in cardiac dysfunction, at least partially by suppressing angiogenesis. Though p53 has been reported to reduce VEGF production by inhibiting hypoxia‐inducible factor, the anti‐angiogenic property of p53 remains to be fully elucidated in cardiomyocytes. To explore the molecular signals downstream of p53 that regulate vascular function, especially under normoxic conditions, DNA microarray was performed using p53‐overexpressing rat neonatal cardiomyocytes. Among genes induced by more than 2‐fold, we focused on CXCL10, an anti‐angiogenic chemokine. Real‐time PCR revealed that p53 upregulated the CXCL10 expression as well as p21, a well‐known downstream target of p53. Since p53 is known to be activated by doxorubicin (Doxo), we examined the effects of Doxo on the expression of CXCL10 and found that Doxo enhanced the CXCL10 expression, accompanied by p53 induction. Importantly, Doxo‐induced CXCL10 was abrogated by siRNA knockdown of p53, indicating that p53 activation is necessary for Doxo‐induced CXCL10. Next, we examined the effect of hypoxic condition on p53‐mediated induction of CXCL10. Interestingly, CXCL10 was induced by hypoxia and its induction was potentiated by the overexpression of p53. Finally, the conditioned media from cultured cardiomyocytes expressing p53 decreased the tube formation of endothelial cells compared with control, analyzed by angiogenesis assay. However, the inhibition of CXCR3, the receptor of CXCL10, restored the tube formation. These data indicate that CXCL10 is a novel anti‐angiogenic factor downstream of p53 in cardiomyocytes and could contribute to the suppression of vascular function by p53.

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Section: Discussionmentioning

confidence: 81%

CXCL10 is a novel anti‐angiogenic factor downstream of p53 in cardiomyocytes

Wahyuni

Tanaka

Igarashi

et al. 2022

Physiological Reports

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“…IP-10 (also known as C-X-C motif chemokine ligand 10, CXCL10) is a chemokine with pro-inflammatory and anti-angiogenic properties, of which the role in the connection between inflammation and angiogenesis has been previously proposed [ 43 ]. The involvement of IP-10 with atherosclerosis and coronary syndromes has also been suggested [ 44 ], and in recently published cohort data, IP-10 has been shown to have a role in heart failure and its associated mortality in African Americans [ 45 ]. Over the last two decades, different studies, both experimental and clinical, have already tried to understand the role of IP-10 in cardiovascular diseases, but its actions are complex and seem to be associated with the type of receptor it binds to [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of New Potential Inflammatory Markers in Patients with Nonvalvular Atrial Fibrillation

Martins

Duarte

Vieira

et al. 2023

IJMS

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Atrial fibrillation (AF), the most common arrhythmia in clinical practice, is associated with an increase in mortality and morbidity due to its high potential to cause stroke and systemic thromboembolism. Inflammatory mechanisms may play a role in the pathogenesis of AF and its maintenance. We aimed to evaluate a range of inflammatory markers as potentially involved in the pathophysiology of individuals with nonvalvular AF (NVAF). A total of 105 subjects were enrolled and divided into two groups: patients with NVAF (n = 55, mean age 72 ± 8 years) and a control group of individuals in sinus rhythm (n = 50, mean age 71 ± 8 years). Inflammatory-related mediators were quantified in plasma samples by using Cytometric Bead Array and Multiplex immunoassay. Subjects with NVAF presented significantly elevated values of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), interferon-gamma, growth differentiation factor-15, myeloperoxidase, as well as IL-4, interferon-gamma-induced protein (IP-10), monokine induced by interferon-gamma, neutrophil gelatinase-associated lipocalin, and serum amyloid A in comparison with controls. However, after multivariate regression analysis adjusting for confounding factors, only IL-6, IL-10, TNF, and IP-10 remained significantly associated with AF. We provided a basis for the study of inflammatory markers whose association with AF has not been addressed before, such as IP-10, in addition to supporting evidence about molecules that had previously been associated with the disease. We expect to contribute to the discovery of markers that can be implemented in clinical practice hereafter.

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“…Chemokines are a group of immune mediators known to mediate cell migration. IP-10 binds to its CXCR3 receptor to induce chemotaxis as well as apoptosis, cell growth and angiostasis [19]. Alterations in IP-10 levels have been associated with in ammatory diseases including infectious diseases, immune dysfunction and tumour development.…”

Section: Discussionmentioning

confidence: 99%

“…Alterations in IP-10 levels have been associated with in ammatory diseases including infectious diseases, immune dysfunction and tumour development. IP-10 is also suggested to play a role in heart failure and in mortality risk in general [19,20].…”

Section: Discussionmentioning

confidence: 99%

Transdiagnostic associations between anger hostility and chemokine interferon-gamma inducible protein 10 (CXCL 10)

Soloey-Nilsen

Nygaard-Odeh

Kristiansen

et al. 2023

Preprint

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Background Many psychiatric disorders are linked to low grade systemic inflammation as measured by systemic cytokine levels. Exploration of cytokines and immune activity and their role in psychiatric symptoms may inform pathobiology and treatment opportunities. Methods This was a cross sectional naturalistic study with 132 participants from a general open inpatient psychiatric ward at the Nordland Hospital Trust, Norway. Serum levels of 28 different cytokines were assessed. Psychiatric symptoms the last week were assessed by a self-rating scale (Symptom check list, SCL-90- R) and grouped in defined clusters. Multiple linear regression model was used for statistical analyses of associations between levels of cytokines and symptoms, adjusting for possible confounding factors. Results We found a positive association (p0.009) between the chemokine interferon-gamma inducible protein 10 (CXCL 10; IP-10) and the anger hostility cluster. No associations were found between the other symptom clusters and cytokines. IP-10 and the anger hostility cluster were positively associated (p 0.002) in the subgroup of patients using psychotropic medication, not in the subgroup not using psychotropic medication. Conclusion Our analyses revealed a significant positive association between the symptom cluster anger hostility in SCL-90-R and the chemokine IP-10 in the subgroup of patients using psychotropic medications.

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Interferon gamma-induced protein 10 (IP-10) and cardiovascular disease in African Americans

Cited by 17 publications

References 62 publications

CXCL10 is a novel anti‐angiogenic factor downstream of p53 in cardiomyocytes

CXCL10 is a novel anti‐angiogenic factor downstream of p53 in cardiomyocytes

Evaluation of New Potential Inflammatory Markers in Patients with Nonvalvular Atrial Fibrillation

Transdiagnostic associations between anger hostility and chemokine interferon-gamma inducible protein 10 (CXCL 10)

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