Inflammaging as a link between autoimmunity and cardiovascular disease: the case of rheumatoid arthritis

Abstract

Currently, traditional and non-traditional risk factors for cardiovascular disease have been established. The first group includes age, which constitutes one of the most important factors in the development of chronic diseases. The second group includes inflammation, the pathophysiology of which contributes to an accelerated process of vascular remodelling and atherogenesis in autoimmune diseases. Indeed, the term inflammaging has been used to refer to the inflammatory origin of ageing, explicitly due to the chronic inflammatory process associated with age (in healthy individuals). Taking this into account, it can be inferred that people with autoimmune diseases are likely to have an early acceleration of vascular ageing (vascular stiffness) as evidenced in the alteration of non-invasive cardiovascular tests such as pulse wave velocity. Thus, an association is created between autoimmunity and high morbidity and mortality rates caused by cardiovascular disease in this population group. The beneficial impact of the treatments for rheumatoid arthritis at the cardiovascular level has been reported, opening new opportunities for pharmacotherapy.

Keywords: arthritis; autoimmune diseases; cardiovascular diseases; inflammation; rheumatoid.

Figure 1

Remodelling of the immune system with ageing. Disturbances in the immunological system are associated with a dysregulation in both the innate and adaptive immune system. Also, the exposome as a cumulative measure of external stimuli and the biological responses throughout the lifespan associated with the genetic background play an important role in the response of the immunological system.

Figure 2

Shared mechanisms in healthy ageing and autoimmune systemic diseases leading to vascular ageing. In the case of autoimmune systemic diseases, inflammatory status (acute-phase reactants, cytokines and adhesion molecules upregulation) and vascular remodelling (high vascular stiffness) are a result of the breakdown self-tolerance due to the mentioned risk factors. While in older healthy adults these immunological and vascular changes are linked with immunosenescence, mitochondrial dysfunction, oxidative stress and DNA damage. *Secondary senescence. EC, endothelial cell; IFN-γ, interferon gamma; IL-1β, interleukin 1 beta; IL-1RA, interleukin 1 receptor antagonist; IL-6, interleukin 6; SASP, senescence-associated secretory phenotype; SNCs: senescent cells; TNF-α, tumour necrosis factor alpha; VSMC, vascular smooth muscle cells.

Figure 3

Inflammation and arterial stiffness. A pro-inflammatory milieu contributes to endothelial dysfunction and vascular remodelling. Arterial stiffness, as the main determinant of vascular age, can be measured by PWV or augmentation indexes. AIX@75, augmentation index adjusted to 75 beats per min; IFN-γ, interferon gamma; IL-1β, interleukin 1 beta, IL-1RA, interleukin 1 receptor antagonist; IL-6, interleukin 6; IL-10, interleukin 10; MMP, metalloproteinases; PWV, pulse wave velocity; TIMPs, metalloproteinases inhibitors; TNF-α, tumour necrosis factor alpha.