Do Antineoplastic Drugs Play an Additional Role in the Progression of Non-Compaction Cardiomyopathy? A Case Report

Non-compaction cardiomyopathy is a rare form of cardiomyopathy;its most common clinical manifestations are heart failure (HF), ventricular arrhythmia, thromboembolism, and sudden cardiac death. We report a rare case of a 63-year-old man with chest tightness, worsening lower leg edema, dyspnea, and decreased exercise tolerance. He had a medical history of gastric cancer treated with subtotal gastrectomy and post-operative chemotherapy with paclitaxel and fluorouracil three years ago. At that time, he was diagnosed with non-compaction cardiomyopathy, and the thickened and reticulated trabecular muscle was exclusively confined to left ventricular apex. Five months ago, he was admitted to our hospital with heart failure and treated for dilated cardiomyopathy, echocardiography revealed severe trabecular noncompact myocardium in both ventricles, which was confirmed by cardiac magnetic resonance imaging (CMR). It is generally accepted that non-compacted myocardium forms in the early embryonic stage, which raises a question in our case whether acquired factors, such as antineoplastic drugs, potentially accelerate the pathological progression of non-compaction cardiomyopathy. Considering there are disparities between current screening tools such as echocardiography and CMR regarding diagnostic criteria, multi-detector CT may be an alternative examination method that could provide a new perspective for diagnosis.

The proatherosclerotic function of indoleamine 2, 3- dioxygenase 1 in the developmental stage of atherosclerosis

The discrepancy of indoleamine 2,3-dioxygenase 1(IDO1)function in atherosclerosis has been noted.Compared to the protective effect of IDO1 against established atherogenesis,the role of IDO1 in the developmental process of atherosclerosis is still unclear.Here,the expression patterns and activities of IDO1 and its isoenzyme tryptophan 2,3-dioxygenase(TDO)in aortas and blood samples of patients with atherosclerosis were investigated.IDO1 and TDO were colocalized with CD3-positive lymphocytes and CD68-positive macrophages in atherosclerotic lesions.The expression and activity of IDO1 and TDO increased with the grade of the histological classification in early atherosclerosis(grade I,II),but the increase did not continue in advanced atherosclerosis(grade III).Treatment of THP-1 macrophages(THP-M)with oxidized low-density lipoprotein(oxLDL)induced the expression of IDO1 via the PI3K/Akt/NF-κB pathway,indicating the potential function of IDO1 in foam cells.Before and after treatment with oxLDL on THP-M,IFN-γ-induced IDO1 exhibited different degrees of promotion on foaming,inflammatory factor production and cell apoptosis.Finally,we found that the IDO1 inhibitor 1-methyl-tryptophan could elevate the high-density lipoprotein cholesterol level in serum and reduce the area of the aortic atherosclerotic lesions in high-fat diet-fed ApoE−/−mice.Our study indicated that IDO1 played a complicated and unfixed role in the entire process of atherogenesis,despite the atheroprotective role in established atherosclerosis.IDO1 also had proatherosclerotic functions in the developmental stages of atherosclerosis.Modulation of IDO1 could be a good method for alleviating atherosclerosis.

Amyloidβneurotoxicity is IDO1–Kyn–AhR dependent and blocked by IDO1 inhibitor

Dear Editor,Alzheimer’s disease(AD),the most common neurodegenerative disorder and a leading cause of dementia is characterized by progressive memory deficits,cognitive impairment and personality changes.The accumulation of extracellular amyloid beta(Aβ)plaques consisted by Aβpeptide and intracellular neurofibrillary tangles(NFTs)composed by misfolded hyperphosphorylated tau are main pathological hallmarks of AD,which ultimately lead to the dysfunction and loss of synapses and the eventual death of neuron.Neuroinflammation plays a causal role in AD pathogenesis.While the mechanism underlying neuroinflammationinduced AD pathology has not been fully elucidated,increasing evidence proposed that the kynurenine pathway(KP),a major route for L-tryptophan(L-Trp)catabolism,plays an important role.