Increased expression of LIGHT/TNFSF14 and its receptors in experimental and clinical heart failure☆

Abstract

Background: Clinical and experimental studies suggest a pathogenic role for inflammation in chronic heart failure (HF). LIGHT is a member of the tumour necrosis factor superfamily involved in innate and adaptive immune responses. Aims: We sought to investigate a potential pathogenic role of LIGHT in chronic HF. Methods: We used various clinical and experimental approaches including studies in post-infarction HF rats and in vitro studies of endothelial cells and peripheral blood mononuclear cells (PBMC). Results: Our main findings were: (i) LIGHT and its receptors (i.e., HVEM and lymphotoxin-β receptor) were regulated during experimental HF, with strong expression in the infarcted area accompanied by up-regulation of HVEM in cardiomyocytes and endothelial cells also in the non-ischaemic part of the left ventricle. (ii) Patients with chronic HF had significantly increased expression of LIGHT on CD3 + T-cells accompanied by increased expression of HVEM on monocytes and within the failing myocardium. (iii) LIGHT induced interleukin (IL)-6 expression in endothelial cells. In HF patients, but not in healthy controls, such an IL-6-inducing effect was also seen in LIGHT activated PBMC. Conclusion: Our findings in both clinical and experimental HF may suggest a role for LIGHT signalling pathways in the progression of chronic HF involving IL-6-related mechanisms.

Atorvastatin Improves Endothelial Function and Cardiac Performance in Patients with Dilated Cardiomyopathy: The Role of Inflammation

“…Chronic heart failure (CHF) is characterized by impaired cardiac performance, neurohormonal imbalance, endothelial dysfunction and inflammation [1,2]. Current therapy for patients with CHF focuses on improving cardiac and exercise performance and correcting neurohormonal imbalances.…”

LIGHT is associated with hypertriglyceridemia in obese subjects and increased cytokine secretion from cultured human adipocytes

“…21,22 Recently, LIGHT signalling pathway has been related with the progression of chronic heart failure involving IL-6-related mechanisms. 23 Tumor necrosis factor is also described as a molecule that causes hypertriglyceridemia and wasting of muscle and fat tissue. 24 In these sense, several studies have implicated the TNF superfamily of pro-inflammatory cytokines in lipid metabolism.…”

Sex-dimorphism in Cardiac Nutrigenomics: effect of Trans fat and/or Monosodium Glutamate consumption

“…Trans -fat feeding deregulated other stress-associated genes in males including phospholipase C δ1, the main cardiac isoform implicated in oxidative stress-induced REDOX signaling [35], and LIGHT/Tnfsf14, demonstrated to be upregulated in clinical and experimental heart failure [36]. Additionally, key circadian clock gene Per1 was decreased by more than half in the hearts of male TFA-fed mice.…”