MicroRNA-29 and an Integrated Understanding of Atrial Fibrillation

The T-cell disorders psoriasis and celiac disease are epidemiologically linked to atrial fibrillation (AF), a known inflammatory and fibrotic disorder.^1,2 Indirect evidence has emerged for a humoral autoimmune pathogenesis for AF.³ We believe that AF, like psoriasis, is in fact a T_H1, T_H17, and T_H22-related autoimmune disorder related to microRNA-ome dysregulation. MicroRNA-29 (mir29), in particular, may lead to an integrated understanding of AF. Liston et al recently highlighted mir29’s role in regulating the polarity of the adaptive immune response.⁴ In the setting of mir29 deficiency, such as seen in AF, T cells are predisposed to an activated TH1 immunophenotype. Atrial biopsies from patients with AF show frequent lymphocytic myocarditis, compatible with this hypothesis.⁵ Flow cytometric findings also support a T-cell etiology, as peripheral blood from AF patients shows upregulation of the T-cell activation markers CD69 and HLA-DR.⁶ Furthermore, microRNA-29 contributes to the fibrotic arrhythmogenic substrate of atrial fibrillation (AF).⁷ Mir29 normally functions to inhibit fibrosis by suppressing mRNA of extracellular matrix genes (including collagens and fibrillin). These new insights into mir29’s functions further support a role for the adaptive immune system in the immunopathogenesis of AF. We recommend that AF investigators team up with immunologists in search for pathogenic T cells.

The authors have no relevant conflicts of interest to disclose.