Promotion of collateral growth (arteriogenesis) by granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with coronary artery disease

Abstract Background Systemic inflammation has a critical role in the development of coronary artery disease (CAD). Identification of inflammatory pathways may provide a platform for novel therapeutic approaches. Purpose We sought to determine whether there are differences in circulating cytokine profiles between patients with CAD and disease-free controls. Methods Study population consisted of 458 patients who underwent diagnostic invasive coronary angiography for clinical indications. Altogether 312 patients had angiographically significant CAD whereas 146 had no angiographically-detected coronary atherosclerosis. We measured the serum concentrations of 48 circulating cytokines. Results Patients with CAD had increased levels of interleukin-1 receptor antagonist (IL-1-RA), interleukin-2 receptor alpha (IL-2Rα), IL-3, IL-4, IL-6, IL-9, IL-10, IL-16, IL-17, IL-18, granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor-BB (PDGF-BB), macrophage inflammatory protein-1-beta (MIP-1-β), tumor necrosis factor-alpha (TNF-α), TNF-β, cutaneous T-cell-attracting chemokine (CTACK), growth regulated oncogene alpha (GRO-α), hepatocyte growth factor (HGF), interferon alpha-2 (IFNα-2), leukemia inhibitory factor (LIF), macrophage colony-stimulating factor (M-CSF), macrophage migration inhibitory factor (MIF), monokine induced by gamma interferon (MIG), beta-nerve growth factor (β-NGF), stem cell factor (SCF) and stromal cell-derived factor 1 alfa (SDF1α). On a logistic multivariate regression model adjusted with age, sex, hypertension and treatment for diabetes, increased levels of IL-4 (p=0.027, OR 1.090), IL-9 (p=0.000, OR 1.013), IL-17 (p=0.011, OR 1.005), CTACK (p=0.008, OR 1.001), MIP-1-β (p=0.004, OR 1.006), GRO-α (p=0.008, OR 1.004), TNF-α (p=0.019, OR 1.011) were independently associated with atherosclerosis. Conclusions Patients with CAD have distinct circulating cytokine profiles compared to disease-free controls. Based on these findings, certain cytokines may have a pivotal role in the development of atherosclerotic cardiovascular disease and cytokine-mediated pathway appear as a promising target for cardiovascular drug development. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Finnish Medical Foundation, Helsinki, Finland; The Finnish Foundation for Cardiovascular Research, Helsinki, Finland

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Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors

Scientific Reports ◽

10.1038/s41598-021-84249-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jani Lappalainen ◽

Nicolas Yeung ◽

Su D. Nguyen ◽

Matti Jauhiainen ◽

Petri T. Kovanen ◽

...

Keyword(s):

Expression Profiles ◽

Gene Expression Profiles ◽

Foam Cells ◽

Colony Stimulating Factor ◽

Human Macrophages ◽

Gm Csf ◽

Macrophage Subpopulations ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

AbstractIn atherosclerotic lesions, blood-derived monocytes differentiate into distinct macrophage subpopulations, and further into cholesterol-filled foam cells under a complex milieu of cytokines, which also contains macrophage-colony stimulating factor (M-CSF) and granulocyte–macrophage-colony stimulating factor (GM-CSF). Here we generated human macrophages in the presence of either M-CSF or GM-CSF to obtain M-MØ and GM-MØ, respectively. The macrophages were converted into cholesterol-loaded foam cells by incubating them with acetyl-LDL, and their atheroinflammatory gene expression profiles were then assessed. Compared with GM-MØ, the M-MØ expressed higher levels of CD36, SRA1, and ACAT1, and also exhibited a greater ability to take up acetyl-LDL, esterify cholesterol, and become converted to foam cells. M-MØ foam cells expressed higher levels of ABCA1 and ABCG1, and, correspondingly, exhibited higher rates of cholesterol efflux to apoA-I and HDL2. Cholesterol loading of M-MØ strongly suppressed the high baseline expression of CCL2, whereas in GM-MØ the low baseline expression CCL2 remained unchanged during cholesterol loading. The expression of TNFA, IL1B, and CXCL8 were reduced in LPS-activated macrophage foam cells of either subtype. In summary, cholesterol loading converged the CSF-dependent expression of key genes related to intracellular cholesterol balance and inflammation. These findings suggest that transformation of CSF-polarized macrophages into foam cells may reduce their atheroinflammatory potential in atherogenesis.

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Growth stimulation of non-small cell lung cancer xenografts by granulocyte-macrophage colony-stimulating factor (GM-CSF)

European Journal of Cancer ◽

10.1016/s0959-8049(98)00236-6 ◽

1998 ◽

Vol 34 (12) ◽

pp. 1958-1961 ◽

Cited By ~ 15

Author(s):

Y. Oshika ◽

M. Nakamura ◽

Y. Abe ◽

Y. Fukuchi ◽

M. Yoshimura ◽

...

Keyword(s):

Lung Cancer ◽

Growth Stimulation ◽

Small Cell ◽

Colony Stimulating Factor ◽

Small Cell Lung ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor ◽

Stimulation Of

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The Truncated Splice Variant of the Granulocyte-Macrophage-Colony-Stimulating Factor Receptor β- Chain in Peripheral Blood Serves as Severity Biomarker of Respiratory Failure in Newborns

Neonatology ◽

10.1159/000513356 ◽

2021 ◽

pp. 1-7

Author(s):

Verena Schulte ◽

Alexandra Sipol ◽

Stefan Burdach ◽

Esther Rieger-Fackeldey

Keyword(s):

Respiratory Failure ◽

Peripheral Blood ◽

Colony Stimulating Factor ◽

Term Infants ◽

Respiratory Impairment ◽

Gm Csf ◽

A Subunit ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

Background: The granulocyte-macrophage-colony-stimulating factor (GM-CSF) plays an important role in surfactant homeostasis. βC is a subunit of the GM-CSF receptor (GM-CSF-R), and its activation mediates surfactant catabolism in the lung. βIT is a physiological, truncated isoform of βC and is known to act as physiological inhibitor of βC. Objective: The aim of this study was to determine the ratio of βIT and βC in the peripheral blood of newborns and its association with the degree of respiratory failure at birth. Methods: We conducted a prospective cohort study in newborns with various degrees of respiratory impairment at birth. Respiratory status was assessed by a score ranging from no respiratory impairment (0) to invasive respiratory support (3). βIT and βC expression were determined in peripheral blood cells by real-time PCR. βIT expression, defined as the ratio of βIT and βC, was correlated with the respiratory score. Results: βIT expression was found in all 59 recruited newborns with a trend toward higher βIT in respiratory ill (score 2, 3) newborns than respiratory healthy newborns ([score 0, 1]; p = 0.066). Seriously ill newborns (score 3) had significantly higher βIT than healthy newborns ([score 0], p = 0.010). Healthy preterm infants had significantly higher βIT expression than healthy term infants (p = 0.019). Conclusions: βIT is expressed in newborns with higher expression in respiratory ill than respiratory healthy newborns. We hypothesize that βIT may have a protective effect in postnatal pulmonary adaptation acting as a physiological inhibitor of βC and, therefore, maintaining surfactant in respiratory ill newborns.

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