Actin Is a Target of T-Cell Reactivity in Patients with Advanced Carotid Atherosclerotic Plaques

Abstract

Atherosclerosis is a chronic inflammatory disease of the arterial wall associated with autoimmune reactions. In a previous study, we observed the presence of actin-specific antibodies in sera from patients with carotid atherosclerosis. To extend our previous results we evaluated the possible role of actin as antigenic target of cell-mediated immune reactions in carotid atherosclerosis. Peripheral blood mononuclear cells (PBMC) from 17 patients and 16 healthy subjects were tested by cell proliferation assay and by ELISA for cytokine production. Actin induced a proliferative response in 47% of patients' PBMC samples, with SI ranging from 2.6 to 21.1, and in none of the healthy subjects' samples (patients versus healthy subjects, P = 0.02). The presence of diabetes in patients was significantly associated with proliferative response to actin (P = 0.04). IFN-γ and TNF-α concentrations were higher in PBMC from patients than in those from healthy subjects and in PBMC proliferating to actin than in nonproliferating ones. Our data demonstrate for the first time a role of actin as a target autoantigen of cellular immune reactions in patients with carotid atherosclerosis. The preferential proinflammatory Th1 activation suggests that actin could contribute to endothelial dysfunction, tissue damage, and systemic inflammation in carotid atherosclerosis.

Ablation of CD8α+ dendritic cell mediated cross-presentation does not impact atherosclerosis in hyperlipidemic mice

“…Moreover, reflective of plaque-directed immunity, different auto-antigens are identified targets of immune responses in atherosclerosis. Oxidized low density lipoprotein (oxLDL) is the most well described 19 , but Tcells isolated from patients with advanced atherosclerosis also respond to F-actin, a known target in necrosis-associated cross-presentation 20 21 . Lastly, a recent study has demonstrated that cytotoxic CD8 + Tcells promote development of a vulnerable atherosclerotic plaque in mice, implicating cytolytic Tcell immunity in plaque destabilization 22 .…”

High Actin Expression in Thrombus of Acute Ischemic Stroke Can Be a Biomarker of Atherothrombotic Origin Stroke

“…The change of actin microfilaments has shown a strong relationship with the reduction of stress fibers and dysfunctional adhesion, causing the accumulation of immune cells and the formation of atherosclerotic plaque (33,34). Recently studies have also suggested that actin is a vital autoantigen target that mediates the autoimmune process of plaque formation and stability in patients with carotid atherosclerosis (35,36).…”

Interleukin-4, hemopexin, and lipoprotein-associated phospholipase A2 are significantly increased in patients with unstable carotid plaque

“…In 2015, Zhao et al showed on animal models that IL-4 might induce macrophages to take on an M2 phenotype to resolve inflammation, thereby protecting against atherosclerosis [45]. In 2013, Profumo found no significant difference in IL-4 levels in patients with carotid atherosclerosis compared to healthy subjects [23]. Recent studies found M1 macrophages to be associated with unstable plaques and M2 macrophages with stable plaques.…”

“…IL-4 regulates macrophage polarization to M2 phenotype, which protects against atherosclerosis. Results of studies assessing the concentration of plasma levels of IL-4 in patients with atherosclerosis have been controversial [22,23].…”