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Objective— Fatty acids (FAs) are the major substrate for energy production in the heart. Here, we hypothesize that capillary endothelial fatty acid binding protein 4 (FABP4) and FABP5 play an important role in providing sufficient FAs to the myocardium. Approach and Results— Both FABP4/5 were abundantly expressed in capillary endothelium in the heart and skeletal muscle. The uptake of a FA analogue, 125I-15-( p -iodophenyl)-3-(R,S)-methyl pentadecanoic acid, was significantly reduced in these tissues in double-knockout (DKO) mice for FABP4/5 compared with wild-type mice. In contrast, the uptake of a glucose analogue, 18F-fluorodeoxyglucose, was remarkably increased in DKO mice. The expression of transcripts for the oxidative catabolism of FAs was reduced during fasting, whereas transcripts for the glycolytic pathway were not altered in DKO hearts. Notably, metabolome analysis revealed that phosphocreatine and ADP levels were significantly lower in DKO hearts, whereas ATP content was kept at a normal level. The protein expression levels of the glucose transporter Glut4 and the phosphorylated form of phosphofructokinase-2 were increased in DKO hearts, whereas the phosphorylation of insulin receptor-β and Akt was comparable between wild-type and DKO hearts during fasting, suggesting that a dramatic increase in glucose usage during fasting is insulin independent and is at least partly attributed to the post-transcriptional and allosteric regulation of key proteins that regulate glucose uptake and glycolysis. Conclusions— Capillary endothelial FABP4/5 are required for FA transport into FA-consuming tissues that include the heart. These findings identify FABP4/5 as promising targets for controlling the metabolism of energy substrates in FA-consuming organs that have muscle-type continuous capillary.

Recent advances in the treatment of pulmonary arterial hypertension provide a rational basis for earlier, noninvasive diagnosis of pulmonary arterial hypertension. However, the reliability of transthoracic echocardiography, plasma BNP levels, and other parameters for the diagnosis of pulmonary arterial hypertension remains unclear. Thus, the purpose of this study was to determine the utility of these modes of investigation for the prediction of pulmonary arterial pressure as compared with the current gold standard, Swan-Ganz catheterization. Among 46 PAH patients, 37 had connective tissue diseases, while the remainder had primary pulmonary arterial hypertension, chronic pulmonary thromboembolism, and interstitial pneumonitis. Systolic pulmonary arterial pressure calculated by transthoracic echocardiography was significantly correlated with systolic pulmonary arterial pressure measured using a Swan-Ganz catheter (r = 0.51, P < 0.01). Plasma BNP concentration did not correlate with systolic pulmonary arterial pressure (r = 0.10, NS) in the overall patient population. However, when we excluded left ventricular heart failure and left ventricular hypertrophy, BNP concentration was correlated with systolic pulmonary arterial pressure (r = 0.508, P < 0.05). Among other variables tested, ECG electrical axis was correlated with pulmonary arterial pressure (r = 0.46, P < 0.05) but uric acid, lactate dehydrogenase, %DLCO, enhanced IIp sound, and pulmonary artery enlargement on chest x-ray did not correlate with pulmonary arterial pressure. These data suggest that echocardiography is the noninvasive modality of choice for the assessment of pulmonary arterial hypertension. Plasma BNP level also predicts pulmonary arterial pressure, when left ventricular heart failure and cardiac hypertrophy are excluded.

A 37-year-old man lost consciousness suddenly due to ventricular fibrillation (VF). After cardioversion, twelve-lead ECG showed a pattern characteristic of type 1 Brugada. An implantable cardioverter defibrillator (ICD) was implanted for Brugada syndrome. In the following three years, VF occurred eight times after consumption of alcohol. Association between the Brugada syndrome and alcohol consumption has rarely been reported. Recently, it was reported that alcohol has inhibitory effect on single cardiac sodium channel gating and it may be that alcohol acted as a sodium channel blocker in this patient. Here we report a case of alcohol-induced VF in Brugada syndrome.

Stent underexpansion is the main predictor of in-stent restenosis (ISR) after drug-eluting stent (DES) placement; however, the predictors of expansion after restenting an ISR lesion have not been reported. ADAPT-DES was a prospective multicenter, real-world registry of 8,582 consecutive pts

症例は74歳,女性.眼,皮膚サルコイドーシスと診断されていた.胸部X線,心電図,心エコー, Gaシンチにて心異常はなかったが, FDG-PETにて心集積を認めた.経過観察中に左脚ブロックを経て完全房室ブロックに進展しステロイド治療を開始した.この際のFDG-PETにて心集積が増強していたが, Gaシンチでは変化なかった. Gaシンチで検出できなかったサルコイドーシスの心病変を, FDG-PETにより早期より観察できた.

During prolonged fasting, fatty acid (FA) released from adipose tissue is a major energy source for peripheral tissues, including the heart, skeletal muscle and liver. We recently showed that FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipocytes and macrophages, are prominently expressed in capillary endothelial cells in the heart and skeletal muscle. In addition, mice deficient for both FABP4 and FABP5 (FABP4/5 DKO mice) exhibited defective uptake of FA with compensatory up-regulation of glucose consumption in these tissues during fasting. Here we showed that deletion of FABP4/5 resulted in a marked perturbation of metabolism in response to prolonged fasting, including hyperketotic hypoglycemia and hepatic steatosis. Blood glucose levels were reduced, whereas the levels of non-esterified FA (NEFA) and ketone bodies were markedly increased during fasting. In addition, the uptake of the 125 I-BMIPP FA analogue in the DKO livers was markedly increased after fasting. Consistent with an increased influx of NEFA into the liver, DKO mice showed marked hepatic steatosis after a 48-hr fast. Although gluconeogenesis was observed shortly after fasting, the substrates for gluconeogenesis were reduced during prolonged fasting, resulting in insufficient gluconeogenesis and enhanced hypoglycemia. These metabolic responses to prolonged fasting in DKO mice were readily reversed by re-feeding. Taken together, these data strongly suggested that a maladaptive response to fasting in DKO mice occurred as a result of an increased influx of NEFA into the liver and pronounced hypoglycemia. Together with our previous study, the metabolic consequence found in the present study is likely to be attributed to an impairment of FA uptake in the heart and skeletal muscle. Thus, our data provided evidence that peripheral uptake of FA via capillary endothelial FABP4/5 is crucial for systemic metabolism and may establish FABP4/5 as potentially novel targets for the modulation of energy homeostasis. Citation: Syamsunarno MRAA, Iso T, Hanaoka H, Yamaguchi A, Obokata M, et al. (2013) A Critical Role of Fatty Acid Binding Protein 4 and 5 (FABP4/5) in the

Factors affecting lumen measurement discrepancy between quantitative coronary angiography (QCA) vs intravascular ultrasound (IVUS) have not been studied. In PROSPECT, grayscale and virtual histology (VH) IVUS imaging of all 3 epicardial arteries was performed and each frame (median interslice

Fatty acid binding protein 4 (FABP4, also designated as adipocyte-FABP or aP2) has been described to be most exclusively expressed in adipocytes and macrophages. Circulating FABP4 levels have been linked to metabolic alternations that are associated adiposity. We have recently reported that FABP4 is

Background Endothelium is a crucial blood–tissue interface controlling energy supply according to organ needs. We investigated whether peroxisome proliferator‐activated receptor‐γ ( PPAR γ) induces expression of fatty acid–binding protein 4 ( FABP 4) and fatty acid translocase ( FAT )/ CD 36 in capillary endothelial cells ( EC s) to promote FA transport into the heart. Methods and Results Expression of FABP 4 and CD 36 was induced by the PPAR γ agonist pioglitazone in human cardiac microvessel EC s ( HCMEC s), but not in human umbilical vein EC s. Real‐time PCR and immunohistochemistry of the heart tissue of control ( Pparg fl/null ) mice showed an increase in expression of FABP 4 and CD 36 in capillary EC s by either pioglitazone treatment or 48 hours of fasting, and these effects were not found in mice deficient in endothelial PPAR γ ( Pparg ∆ EC /null ). Luciferase reporter constructs of the Fabp4 and CD 36 promoters were markedly activated by pioglitazone in HCMEC s through canonical PPAR ‐responsive elements. Activation of PPAR γ facilitated FA uptake by HCMEC s, which was partially inhibited by knockdown of either FABP 4 or CD 36. Uptake of an FA analogue, 125 I‐ BMIPP , was significantly reduced in heart, red skeletal muscle, and adipose tissue in Pparg ∆ EC /null mice as compared with Pparg fl/null mice after olive oil loading, whereas those values were comparable between Pparg fl/null and Pparg ∆ EC /null null mice on standard chow and a high‐fat diet. Furthermore, Pparg ∆ EC /null mice displayed slower triglyceride clearance after olive oil loading. Conclusions These findings identified a novel role for capillary endothelial PPAR γ as a regulator of FA handing in FA ‐metabolizing organs including the heart in the postprandial state after long‐term fasting.

The mechanism and patterns of in-stent restenosis (ISR) comparing bare metal stents (BMS) and 1st and 2nd generation drug-eluting stent (DES) as evaluated by intravascular ultrasound (IVUS) have not been well delineated. IVUS evaluation of in-stent restenosis (ISR) included core-lab based

Adaptive servo ventilation (ASV) has been successfully used for treating heart failure (HF) in patients with central sleep apnea. However, it remains what factors are the most important predictors of fatal cardiovascular events after ASV therapy. The Integrated Area of Desaturation (IAD) index is