Toll-like receptors and myocardial contractile dysfunction

Abstract

Editorial commentary on ‘Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of Toll-like receptor 9.’ (Knuefermann et al. ,9 pp. 26–35, this issue). Toll-like receptors (TLRs), vertebrate homologues of the drosophila Toll receptor, have been shown to play essential roles in the innate immune response.1 As TLRs recognize pathogen-associated molecular patterns (PAMPs), they are also known as pattern recognition receptors (PRRs). So far, 11 members of human TLRs have been identified.1 Roles of TLRs have been vigorously studied also in the area of cardiovascular sciences, and these molecules are responsible for the genesis of a variety of cardiovascular disorders, including myocardial dysfunction during sepsis, ischaemia/reperfusion, heart failure, cardiac hypertrophy, and atherosclerosis.2–4 Among the TLRs, TLR2 and TLR4 have been investigated most extensively. TLR2 recognizes gram-positive bacterial lipoproteins and peptideglycan, and lipopolysaccharide, endotoxin, is one of the PAMPs for TLR4. These TLR2 and TLR4 are shown to contribute to myocardial contractile dysfunction during sepsis. Activation of inflammatory cytokines and nuclear factor κB (NF-κB) as well as augmented expression of inducible nitric oxide synthase (iNOS) are the major consequences of the stimulation of these TLRs. Expression of TLR4 was augmented in the myocardium form patients with heart failure,5 and TLR4 was involved in the genesis of myocardial hypertrophy.6 … * Corresponding author. Tel: +81 3 3320 2200; fax: +81 3 3370 8501. E-mail address : toshitak-tky{at}umin.ac.jp