Postnatal cardiomyocytes have only limited capacity of proliferation. Therefore, the myocardium is intrinsically equipped with cardioprotective machineries and protects itself from pathological stresses. One of the most important cardioprotective systems is the signal network of autocrine/paracrine factors, including neurohumoral
factors, growth factors, and
cytokines. In this review, we focus on the roles of
interleukin-6 (IL-6) family
cytokines, also known as
glycoprotein 130 (gp130)
cytokines, in cardioprotection. These
cytokines make a complex with their specific
cytokine receptor α-subunits. The
cytokine-receptor α-subunit complex binds to gp130, a common receptor of the
IL-6 family, followed by the activation of JAK/STAT, ERK, and
PI3 kinase/Akt pathways. In cardiomyocytes, signals through gp130 promote cell survival and angiogenesis through the JAK/STAT pathway. Activation of gp130 in cardiac stem cells induces their endothelial transdifferentiation, leading to neovascularization. Recently, accumulating evidence has revealed that altered JAK/STAT activity is associated with
heart failure, suggesting that the JAK/STAT pathway is a therapeutic target against
cardiovascular diseases. Interestingly, activation of the JAK/STAT pathway with
interleukin-11 (IL-11) exhibits preconditioning effects in
ischemia/reperfusion model. Moreover,
IL-11 treatment after coronary
ligation prevents cardiac remodeling through the JAK/STAT pathway. Since
IL-11 is used for patients with
thrombocytopenia, we propose that
IL-11 is a candidate
cytokine clinically available for cardioprotection
therapy.