Figure 3.

Proposed pathophysiological mechanisms that could explain the presence or absence of response to treatment in myocarditis. (A) Represents the scenario proposed in patients with response to treatment; in these patients there is an up-regulation of CAR mRNA levels, which has been related to the STAT1 signaling pathway, as well as a greater inflammatory response mediated by JNK and p38MAPK with increased synthesis of interferon gamma (INF-γ), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and nitric oxide synthase (iNOS); thus, CAR induces signals that activate cellular effectors and cytokine responses characteristic of innate or acquired immunity independently of viral infection type. In this sense, the use of immunosuppressants or immunomodulators may be important because it blocks the inflammatory effect of the over-expression of CAR mRNA levels without affecting its cellular adhesion molecule function, which has been associated with the healing phase or regeneration of damaged myocardium. (B) Represents the scenario in patients without response to treatment; in these patients there is a lower transcription of CAR; however, the rest of the pathophysiological pathway is still unknown [modified from Ghigo et al (36)].