Tofacitinib ameliorates atherosclerosis and reduces foam cell formation in apoE deficient mice

Wang, Zaicun; Wang, Shumei; Wang, Zunzhe; Yun, Tiantian; Wang, Chenchen; Wang, Huating

doi:10.1016/j.bbrc.2017.06.020

Cited by 29 publications

(14 citation statements)

References 18 publications

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“…Thus, in accordance with our results, a recent work inducing epitope-specific Treg cells via vaccination was atheroprotective without affecting blood lipids (60). Moreover, not only the relevant CANTOS study, but also a number of immunomodulatory interventions in animal models, such as other Treg-inducer (61), a TLR4 inhibitor (62), an antiplatelet agent (63), NLRP3 inflammasomedirected therapies (64,65) or a M2 macrophage-inducing kinase inhibitor (66) exerted atheroprotection in the absence of lipid-modifying effects, suggesting that lipid-lowering effects of immune-mediated treatments are possibly the exception rather than the rule.…”

Section: Discussionsupporting

confidence: 88%

Reformulating Small Molecules for Cardiovascular Disease Immune Intervention: Low-Dose Combined Vitamin D/Dexamethasone Promotes IL-10 Production and Atheroprotection in Dyslipidemic Mice

et al. 2020

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Ospina-Quintero et al. Regulatory Cell-Inducing Small Molecule Formulation non-immunosuppressive, low-dose of VitD/Dexa, administered subcutaneously and repetitively, exerts atheroprotective effects in dyslipidemic mice, apparently due to the induction of an IL-10-producing network of lymphoid and myeloid immune cells. These well known, widely available, and inexpensive small molecules can be easily coformulated into a simple and accessible agent with a potential use as a prophylactic or therapeutic immune intervention for CVD and other chronic inflammatory diseases.

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Section: Discussionsupporting

confidence: 88%

Reformulating Small Molecules for Cardiovascular Disease Immune Intervention: Low-Dose Combined Vitamin D/Dexamethasone Promotes IL-10 Production and Atheroprotection in Dyslipidemic Mice

et al. 2020

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“…In agreement with this observation, in vitro experiments and in vivo animal models revealed that tofacitinib up-regulated ABCA1 expression, promoted anti-inflammatory macrophage polarization, improved EC function, and attenuated atherosclerosis (Table 1 and Fig. 3;De Vries et al, 2019;Furumoto et al, 2017;Pérez-Baos et al, 2017;Wang et al, 2017). However, recently the Oral Surveillance study revealed a statistically significant and clinically relevant increase in pulmonary embolism and an increased mortality in patients older than 50 yr with an increased CV risk when treated with a tofacitinib dose of 10 mg twice daily ( Fig.…”

Section: Anti-ifn/ifnar Signaling Therapiessupporting

confidence: 76%

Type-I interferons in atherosclerosis

Chen

Tas

Winther

2019

Journal of Experimental Medicine

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The contribution of dyslipidemia and inflammation in atherosclerosis is well established. Along with effective lipid-lowering treatments, the recent success of clinical trials with anti-inflammatory therapies and the accelerated atherosclerosis in many autoimmune diseases suggest that targeting inflammation may open new avenues for the prevention and the treatment for cardiovascular diseases (CVDs). In the past decades, studies have widened the role of type-I interferons (IFNs) in disease, from antivirus defense to autoimmune responses and immuno-metabolic syndromes. While elevated type-I IFN level in serum is associated with CVD incidence in patients with interferonopathies, experimental data have attested that type-I IFNs affect plaque-residing macrophages, potentiate foam cell and extracellular trap formation, induce endothelial dysfunction, alter the phenotypes of dendritic cells and T and B lymphocytes, and lead to exacerbated atherosclerosis outcomes. In this review, we discuss the production and the effects of type-I IFNs in different atherosclerosis-associated cell types from molecular biology studies, animal models, and clinical observations, and the potential of new therapies against type-I IFN signaling for atherosclerosis.

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“…The present results showed that Tofacitinib totally prevented AIAassociated aortic ED. This new data is in agreement with studies in which JAK inhibition was reported to reduce the expression of adhesion molecules in cultured endothelial cells exposed to TNFα (34) or oxidized-LDL (35), and to alleviate plaque burden in a model of atherosclerosis (36). Furthermore, in line with the current guidelines recommending an aggressive control of disease activity for CV risk reduction in RA, we reported a negative correlation between arthritis score and endothelial function.…”

Section: Discussionsupporting

confidence: 92%

Vascular and cerebral benefits of Tofacitinib in rheumatoid arthritis: evidence in rat adjuvant-induced arthritis

Totoson¹,

Quirié²,

Pedard³

et al. 2020

Preprint

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Background: To determine vascular and cerebral effects of Tofacitinib in the adjuvant-induced arthritis (AIA) model in rat.Methods: At the first signs of arthritis (day 10-12 post-immunization), Tofacitinib (10 mg/kg s.c., twice daily) or vehicle were administered for 3 weeks in AIA rats. A group of non AIA served as controls. Body weights and arthritis scores were daily monitored. Anhedonia was explored with the saccharin preference test at day 4 (preclinical), day 11 (early) and day 28 (acute arthritis) post-immunization. At the end of the treatment, aorta, brain and blood were collected for analysis of endothelial function using acetylcholine (Ach)-induced relaxation, brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus (Hip) and prefrontal cortex (PFC), and IL-1β, TNFα, IL-17A plasma levels. Radiographic score of paws was also assessed. Results: As compared to vehicle, Tofacitinib reduced body weight loss, arthritis and radiographic scores (p<0.001) but did not change plasma levels of pro-inflammatory cytokines. Tofacitinib fully prevented AIA-associated reduction in Ach-induced relaxation. As compared to controls, vehicle-treated AIA exhibited low BDNF levels in PFC (p<0.001) and anhedonia at all times examined (p<0.05). Tofacinib did not improve anhedonia, but resulted in elevation of BDNF levels both in PFC (p<0.05) and Hip (p<0.001). A positive correlation was observed between brain BDNF levels and endothelial function (p<0.05).Conclusion: Restoration of normal endothelial function and elevation of brain BDNF levels by Tofacitinib in AIA rats support a positive effect of this new antirheumatic drug on cardiovascular and neuropsychiatric comorbidities of rheumatoid arthritis.

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Tofacitinib ameliorates atherosclerosis and reduces foam cell formation in apoE deficient mice

Cited by 29 publications

References 18 publications

Reformulating Small Molecules for Cardiovascular Disease Immune Intervention: Low-Dose Combined Vitamin D/Dexamethasone Promotes IL-10 Production and Atheroprotection in Dyslipidemic Mice

Reformulating Small Molecules for Cardiovascular Disease Immune Intervention: Low-Dose Combined Vitamin D/Dexamethasone Promotes IL-10 Production and Atheroprotection in Dyslipidemic Mice

Type-I interferons in atherosclerosis

Vascular and cerebral benefits of Tofacitinib in rheumatoid arthritis: evidence in rat adjuvant-induced arthritis

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