4.1. Th17 cells and MI/IR
Myocardial infarction (MI), which is caused by acute and persistent
ischemia and myocardial hypoxia [40]. Studies have found that Th17
cells are significantly increased on 14 days after myocardial infarction
in mice. Th17 cells help the host to fight infection by recruiting
neutrophils and macrophages into the infected tissue. The expression of
inflammatory cytokines such as IL-6, IL-1β and TNF-α, induced or
enhanced by Th17 cells, promote extracellular matrix remodelling by
producing repair-related components such as MMP or proteoglycan(Figure
4). In rat models of myocardial infarction, Th17 cells were found to
induce increased myocardial fibrosis through secretion of IL-17A and
IL-17F. IL-17A could also promote fibrosis by promoting inflammatory
cytokines, continuous infiltration of neutrophils and macrophages.
trigger recruitment and activation of cardiac immune cells to the
damaged site. Cell-based cardiac repair therapy enhances the cardiac
function of the damaged heart muscle, but the mechanism remains
controversial. In the rat model of heart failure (HF) induced by
intraperitoneal injection of isoacrylate, the blockade of IL-17
production led to a decrease in myocardial fibrosis. Th17 cells may
regulate myocardial fibrosis by producing MMP through the IL-17- NF-κB
ligand (RANKL)/osteosinase (OPG) system in the cardiac
fibroblasts[41]. Studies showed that the proportion of Th17 cells
was significantly higher in the acute myocardial infarction (AMI) group
compared with stable angina and healthy controls, and the proportion of
Th17 cells also showed a positive correlation with IL-17 levels,
indicating that Th17 cells participated in AMI development, and
increased IL-17A led to increased mortality[42]. Myocardial
reperfusion is the most important method to prevent cell death after
myocardial ischemia. However, blood flow recovery may paradoxically lead
to myocardial ischemia-reperfusion injury, accompanied by metabolic
disturbances and cardiomyocyte death[43]. Both circulating Th17
cells and IL-17 levels are increased in ACS patients compared to healthy
controls and stable angina patients. Most studies have concluded that
high circulating levels of IL-17A circulation are associated with poor
clinical outcomes. IL-17 aggravated myocardial ischemia-reperfusion
injury, mainly related to IL-17 affecting Bax/Bcl-2 balance, promoting
myocardial apoptosis, activation of cardiac endothelial cell E-selectors
and ICAM-1 expression promoting neutrophil-endothelial cell adhesion and
induction of chemokine expression, mediated local myocardial
infiltration of neutrophils. Furthermore, IL-18 binding protein
(IL-18BP) is a secreted 40 kDa glycoprotein. IL-18BP improves IR injury
to the heart by inhibiting parts of Th17 differentiation[44]. In
particular, cell recruitment (i.e. chemokine blockade) may be a powerful
therapeutic strategy to reduce myocardial reperfusion injury at the
onset of reperfusion[45].