Toll-like receptors (TLRs), a family of pattern-recognition receptors involved in the innate immune response, are expressed in immune cells and solid tissues, including cardiomyocytes. Widespread activation of inflammatory cells at the systemic level and in the heart causes the release of proinflammatory cytokine mediators which negatively influence heart function. Monocyte TLR4 and TLR2 expression and plasma inflammatory protein levels of BNP, CRP, LDH and NOX4 as
well as plasma microRNA miR320a, are positively correlated with cardiac injury or dysfunction.
We studied the correlation between the levels of TLR4 found in the blood and heart taken from patients during coronary artery bypass graft surgery with impaired cardiac function. The control group was composed of patients with moderate heart function, with an ejection fraction (EF) > 55% (HIGH EF) compared to patients with lower EF < 45% (LOW EF).
All the patients were recruited again after a year for follow up tests. Auricles obtained during heart surgery were tested for TLR2 and TLR4 gene expression. A significant inverse correlation between TLR4 (monocytes protein and heart mRNA) and cardiac function was observed (p<0.05). In addition plasma levels of miR320a and BNP correlated with the severity of heart failure (HF). Nocorrelation was observed with TLR2, CRP, LDH and EF. Monocyte TLR4 of the follow up group was reduced only in the patients where EF was improved. These results reflect the involvement of TLR4 in the development of left ventricular dysfunction. Monocytes TLR4 may serve as an additional biomarker for the severity of HF.
Keywords: Heart failure; TLR4; BNP; miR320a