Translational mini-review series on immunology of vascular disease: inflammation, infections and Toll-like receptors in cardiovascular disease.

Cardiovascular Research Unit, The University of Sheffield, Sheffield, UK.
Clinical & Experimental Immunology (Impact Factor: 3.28). 04/2009; 156(3):386-94. DOI: 10.1111/j.1365-2249.2009.03886.x
Source: PubMed

ABSTRACT Cardiovascular disease, in which atherosclerosis is the major underlying cause, is currently the largest cause of death in the world. Atherosclerosis is an inflammatory disease characterized by the formation of arterial lesions over a period of several decades at sites of endothelial cell dysfunction. These lesions are composed of endothelial cells, vascular smooth muscle cells, monocytes/macrophages and T lymphocytes (CD4(+)). As the lesions progress some can become unstable and prone to disruption, resulting in thrombus formation and possibly a myocardial infarction or stroke depending upon the location. Although the exact triggers for plaque disruption remain unknown, much recent evidence has shown a link between the incidence of myocardial infarction and stroke and a recent respiratory tract infection. Interestingly, many reports have also shown a link between a family of pattern recognition receptors, the Toll-like receptors, and the progression of atherosclerosis, suggesting that infections may play a role in both the progression of atherosclerosis and in inducing the more severe complications associated with the disease.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Macrophage-derived foam cell formation is a hallmark of atherosclerosis. It has been reported that oxidized low density lipoprotein (oxLDL) inducing formation of foam cells and expression of inflammatory molecules are partly mediated by toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway. However, whether oxLDL/β2-glycoprotein I/anti-β2-glycoprotein I (oxLDL/β2GPI/anti-β2GPI) complex enhanced formation of foam cells involving TLR4/NF-κB pathway or not has never been explored. In the current study, we focused on investigating the transformation of peritoneal macrophages from BALB/c mice into foam cells induced by the three complexes, and the involvement of TLR4 as well as its downstream signal molecule NF-κB. The results showed that treatment of macrophages with oxLDL/β2GPI/anti-β2GPI complex could markedly increase intracellular lipid loading and expression of TLR4, phosphorylated NF-κB p65 (p-NF-κB p65), monocyte chemoattractant protein-1 (MCP-1), as well as tissue factor (TF). The oxLDL and oxLDL/β2GPI/anti-β2GPI complex induced formation of foam cells and expression of p-NF-κB p65 were significantly reduced, while macrophages were pre-treated with TLR4 inhibitor TAK-242. Meanwhile, both TAK-242 and NF-κB inhibitor PDTC could remarkably inhibit oxLDL, oxLDL/β2GPI/anti-β2GPI complex, as well as LPS increased MCP-1 and TF levels. Nevertheless, β2GPI/anti-β2GPI complex-induced MCP-1 and TF mRNA expression were inhibited by TAK-242 rather than PDTC, although TF activity was significantly reduced by both of the inhibitors. In conclusion, our results indicate that oxLDL/β2GPI/anti-β2GPI complex could enhance the conversion of macrophages into foam cells and the process may be at least partly mediated by TLR4/NF-κB pathway, which may contribute to the accelerated development of atherosclerosis in APS.
    Thrombosis Research 05/2014; · 2.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Vascular inflammation contributes to the defense against invading microbes and to the repair of injured tissues. In most cases it resolves before becoming apparent. Vasculitis comprises heterogeneous clinical entities that are characterized by the persistence of vascular inflammation after it has served its homeostatic function. Most underlying mechanisms have so far remained elusive. Intravascular immunity refers to the surveillance of the vasculature by leukocytes that sense microbial or sterile threats to vessel integrity and initiate protective responses, that entail most events that determine the clinical manifestations of vasculitis, such as end-organ ischemia, Neutrophil Extracellular Traps generation and thrombosis, leukocyte extravasation and degranulation. Understanding how the resolution of vascular inflammation goes awry in patients with systemic vasculitis will facilitate the identification of novel pharmacological targets and bring us a step closer in each patient to the selection of more effective and less toxic treatments.
    Clinical & Experimental Immunology 10/2013; · 3.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: During this era of unprecedented antiretroviral therapeutic efficacy, there is hope for successfully treated individuals to achieve a longevity approaching that of the general population. However, the recent identification of a higher incidence of cardiovascular, bone, metabolic, neurocognitive and other aging comorbidities is of major concern and may compromise that ability. The purpose of this review is to focus on the dynamic process of immune remodelling, known as immune senescence, which occurs during HIV infection, and how it impacts on long-term comorbidities.
    Current Opinion in HIV and AIDS 05/2014; · 4.39 Impact Factor

Full-text (2 Sources)

Available from
Jun 3, 2014