Toll-Like Receptor 4 Stimulation Initiates an Inflammatory Response That Decreases Cardiomyocyte Contractility

Abstract

Toll-like receptors (TLRs) have been identified as primary innate immune receptors for the recognition of pathogen-associated molecular patterns by immune cells, initiating a primary response toward invading pathogens and recruitment of the adaptive immune response. TLRs, especially Toll-like receptor 4 (TLR4), can also be stimulated by host-derived molecules and are expressed in the cardiovascular system, thus acting as a possible key link between cardiovascular diseases and the immune system. TLR4 is involved in the acute myocardial dysfunction caused by septic shock and myocardial ischemia. We used wild-type (WT) mice, TLR4-deficient (TLR4-knockout [ko]) mice, and chimeras that underwent myeloablative bone marrow transplantation to dissociate between TLR4 expression in the heart (TLR4-ko/WT) and the immunohematopoietic system (WT/TLR4-ko). Following lipopolysaccharide (LPS) challenge (septic shock model) or coronary artery ligation, myocardial ischemia (MI) model, we found WT/TLR4-ko mice challenged with LPS or MI displayed reduced cardiac function, increased myocardial levels of interleukin-1β and tumor necrosis factor-α, and upregulation of mRNA encoding TLR4 prior to myocardial leukocyte infiltration. The cardiac function of TLR4-ko or WT/TLR4-ko mice was less affected by LPS and demonstrated reduced suppression by MI compared with WT. These results suggest that TLR4 expressed in the cardiomyocytes plays a key role in this acute phenomenon.

Up‐regulated TLR4 in cardiomyocytes exacerbates heart failure after long‐term myocardial infarction

“…14 and Avlas et al . 35 reported that cardiomyocyte TLR4, rather than leucocyte TLR4, plays a greater role in cardiac inflammation and dysfunction caused by either LPS or coronary artery ligation. In contrast, Tavener et al .…”

CD4 + T Cells Promote the Transition From Hypertrophy to Heart Failure During Chronic Pressure Overload

“…In experimental autoimmune myocarditis, T lymphocytes and dendritic cells (DCs) have been demonstrated to be obligatory contributors of autoimmune response to tissue damage. 8,9 DCs possess a strong capacity to ingest external antigens and to present them through the major histocompatibility complex class II (MHCII) complex to induce Background-The mechanisms by which the heart adapts to chronic pressure overload, producing compensated hypertrophy and eventually heart failure (HF), are still not well defined. We aimed to investigate the involvement of T cells in the progression to HF using a transverse aortic constriction (TAC) model.…”

Early sepsis does not stimulate reactive oxygen species production and does not reduce cardiac function despite an increased inflammation status

“…A more recent hypothesis has however emerged: bacterial lipopolysaccharides inhibit the contractility of isolated cardiomyocytes through a stimulation of the NFκB pathway (Avlas et al. 2011; Hobai et al. 2015).…”