Type-I interferons in atherosclerosis

Abstract

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.

Blockade of Macrophage CD147 Protects Against Foam Cell Formation in Atherosclerosis

“…Increasing studies suggest that atherosclerosis is a chronic inflammatory disease of large and medium arteries, with characteristic foam cell formation due to cholesterol accumulation ( Chen et al, 2020 ; Ma et al, 2020 ). Therefore, inhibiting foam cell formation is a fundamental step in slowing the progression of atherosclerotic plaques.…”

Myeloid Cell Diversity and Impact of Metabolic Cues during Atherosclerosis

“…Genetic pDC depletion, following diptheria toxin administraton in BDCA2-DTR atherogenic mice, led to increased lesion area [175]. Moreover, TLRinduced IFN-I production by pDCs is triggered by neutrophils NETs in human atherosclerotic plaque [178]. All together, these data suggest that…”

COVID-19, rheumatic diseases and immune dysregulation—a perspective

“…Based on the role of IFN responses in viral infection, the increased IFN signals in active rheumatic diseases may be theorised to assist with viral clearance during an infection. Intriguingly, aging results in diminished type I interferon responses intracellularly [21]. Recently, inborn errors against type I interferon immunity [22] and autoantibodies against type I interferon [23] have been detected in patients with severe COVID-19 in contrast to patients with mild/asymptomatic disease, suggesting that impaired interferon response plays a key role in disease pathogenesis.…”