Differential regulation of diacylglycerol kinase isoform in human failing hearts.

Evidence from several studies indicates the importance of Gαq protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG), and protein kinase C, in the development of heart failure. DAG kinase (DGK) acts as an endogenous regulator of GPCR signaling pathway by catalyzing and regulating DAG. Expressions of DGK isoforms α, ε, and ζ in rodent hearts have been detected; however, the expression and alteration of DGK isoforms in a failing human heart has not yet been examined.

Serum YKL-40 predicts adverse clinical outcomes in patients with chronic heart failure.

Background: Human cartilage glycoprotein-39 (YKL-40), a novel inflammatory marker, is secreted into circulation by macrophages, neutrophils, chondrocytes, vascular smooth muscle cells and cancer cells. Circulating levels of YKL-40 are related to the degree of inflammation, tissue remodeling, fibrosis, and cancer progression.

Methods And Results: We examined serum YKL-40 levels in 121 patients with chronic heart failure (CHF) and 39 control subjects.

Risk stratification of chronic heart failure patients by multiple biomarkers: implications of BNP, H-FABP, and PTX3.

Background: B-type natriuretic peptide (BNP), heart-type fatty acid-binding protein (H-FABP), and pentraxin 3 (PTX3) each predict adverse cardiac events in chronic heart failure (CHF) patients. For prognostic evaluation from different aspects, the utility of combined measurement of the 3 biomarkers in patients with CHF was examined in the present study.

Methods And Results: Levels of BNP (associated with left ventricular dysfunction, positive if >200 pg/ml), H-FABP (marker of myocardial damage, positive if >4.

Relation of serum heat shock protein 60 level to severity and prognosis in chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Heat shock protein (HSP) 60 is induced by a variety of stressors, including oxidative stress and inflammation, and it plays a protective role against stress-induced cardiomyocyte injury. Recently, it has been reported that HSP 60 exists in the circulation. Chronic heart failure (CHF) is characterized by systemic abnormalities, and the myocardium is exposed to various stressors.

High-mobility group box 1 restores cardiac function after myocardial infarction in transgenic mice.

Aims: High-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein and is released from necrotic cells, inducing inflammatory responses and promoting tissue repair and angiogenesis. To test the hypothesis that HMGB1 enhances angiogenesis and restores cardiac function after myocardial infarction (MI), we generated transgenic mice with cardiac-specific overexpression of HMGB1 (HMGB1-Tg) using alpha-myosin heavy chain promoter.

Methods And Results: The left anterior descending coronary artery was ligated in HMGB1-Tg and wild-type littermate (Wt) mice.

Diacylglycerol kinase-epsilon restores cardiac dysfunction under chronic pressure overload: a new specific regulator of Galpha(q) signaling cascade.

Galpha(q) protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG) and protein kinase C (PKC), plays a critical role in cardiac hypertrophy. DAG kinase (DGK) catalyzes DAG phosphorylation and controls cellular DAG levels, thus acting as a regulator of GPCR signaling. It has been reported that DGKepsilon acts specifically on DAG produced by inositol cycling.

Diacylglycerol kinase zeta inhibits myocardial atrophy and restores cardiac dysfunction in streptozotocin-induced diabetes mellitus.

Background: Activation of the diacylglycerol (DAG)-protein kinase C (PKC) pathway has been implicated in the pathogenesis of a number of diabetic complications. Diacylglycerol kinase (DGK) converts DAG to phosphatidic acid and acts as an endogenous regulator of PKC activity. Akt/PKB is associated with a downstream insulin signaling, and PKCbeta attenuates insulin-stimulated Akt phosphorylation.