Interaction of epoxyeicosatrienoic acids and adipocyte fatty acid-binding protein in the modulation of cardiomyocyte contractility.

BACKGROUND: Adipocyte fatty acid-binding protein (FABP4) is a member of a highly conserved family of cytosolic proteins that bind with high affinity to hydrophobic ligands, such as saturated and unsaturated long-chain fatty acids and eicosanoids. Recent evidence has supported a novel role for FABP4 in linking obesity with metabolic and cardiovascular disorders. In this context, we identified FABP4 as a main bioactive factor released from human adipose tissue that directly suppresses heart contraction in vitro. As FABP4 is known to be a transport protein, it cannot be excluded that lipid ligands are involved in the cardiodepressant effect as well, acting in an additional and/or synergistic way. OBJECTIVE: We investigated a possible involvement of lipid ligands in the negative inotropic effect of adipocyte factors in vitro. RESULTS: We verified that blocking the CYP epoxygenase pathway in adipocytes attenuates the inhibitory effect of adipocyte-conditioned medium (AM) on isolated adult rat cardiomyocytes, thus suggesting the participation of epoxyeicosatrienoic acids (EETs) in the cardiodepressant activity. Analysis of AM for EETs revealed the presence of 5,6-, 8,9-, 11,12- and 14,15-EET, whereas 5,6-EET represented about 45% of the total EET concentration in AM. Incubation of isolated cardiomyocytes with EETs in similar concentrations as found in AM showed that 5,6-EET directly suppresses cardiomyocyte contractility. Furthermore, after addition of 5,6-EET to FABP4, the negative inotropic effect of FABP4 was strongly potentiated in a concentration-dependent manner. CONCLUSIONS: These data suggest that adipocytes release 5,6-EET and FABP4 into the extracellular medium and that the interaction of these factors modulates cardiac function. Therefore elevated levels of FABP4 and 5,6-EET in obese patients may contribute to the development of heart dysfunction in these subjects.

Adipocyte-derived factors suppress heart contraction.

BACKGROUND: Obesity is strongly associated with cardiovascular diseases including systemic hypertension, coronary artery disease and heart failure. Despite several investigations the pathophysiological mechanisms involved remain unclear. We have previously shown that adipose tissue exerts a highly potent activity with an acute depressant effect on cardiomyocytes, thus suggesting direct involvement of adipose tissue in the development of heart dysfunction. OBJECTIVE AND DESIGN: This study investigates the effects of adipocyte factors obtained from subcutaneous adipose tissue on the whole cardiac function by using isolated perfused rat hearts in a Langendorff mode. We recorded changes in coronary flow, developed isovolumetric left ventricular pressure, contraction rate and relaxation rate. RESULTS: We observed a significant decrease in heart contractility parameters as well as in coronary flow within a few seconds of incubation with adipocyte factors. The cardiodepressant effects could not be blocked by the nonselective cyclooxygenase-inhibitor indomethacin. Human adipocytes release tumor necrosis factor-α, interleukin-6 (IL-6) and IL-1ß into extracellular medium. These cytokines were tested for their potential effect but were, however, not responsible for the cardiodepressant effect observed. CONCLUSION: These data indicate that human adipocytes secrete factors with a strong acute depressant effect on cardiac force generation and coronary flow due to contraction of the coronary vessels, thus suggesting a direct role of adipose tissue in the pathogenesis of cardiac dysfunction.

Role of primary care providers in dengue prevention and control in the community.

Dengue fever is a major public health threat in Malaysia, especially in the highly urbanized states of Selangor and the Federal Territory of Kuala Lumpur. It is believed that many seek treatment at the primary care clinics and are not admitted. This study aims at establishing the fact that primary care practitioners, as the first point of patient contacts, play a crucial role in advising patients suspected of having dengue to take early preventive measures to break the chain of dengue transmission. A total of 236 patients admitted to two government hospitals for suspected dengue fever were interviewed using a structured questionnaire over a one week period in December 2008. It was found that 83.9% of the patients had sought treatment at a Primary Care (PC) facility before admission to the hospital, with 68.7% of them seeking treatment on two or more occasions. The mean time period for seeking treatment at primary care clinic was one and a half (1.4) days of fever, compared to almost five (4.9) days for admission. The majority of patients (96-98%) reported that primary care practitioners had not given them any advice on preventive measures to be taken even though 51.9% of the patients had been told they could be having dengue fever. This study showed the need for primary care providers to be more involved in the control and prevention of dengue in the community, as these patients were seen very early in their illness compared to when they were admitted.

Lipoprotein apheresis reduces adipocyte fatty acid-binding protein serum levels.

BACKGROUND AND METHODS: Adipocyte fatty acid-binding protein (FABP4) is a member of the intracellular lipid-binding protein family highly expressed in adipocytes and macrophages. Recent studies indicate a key role for circulating FABP4 in the pathogenesis of atherosclerosis and type 2 diabetes. We described an additional role for FABP4 in the development of cardiac dysfunction in obesity. Therefore, FABP4 seems to be a target in the prevention and treatment of metabolic and cardiovascular disorders in obesity with high potential for future therapeutic applications. However, a safe pharmacological therapy is not yet available. Lipoprotein apheresis is an established therapy for severe and otherwise untreatable hypercholesterolemia which increases life expectancy in patients at high-risk for cardiovascular events. We therefore investigated the acute effect of lipoprotein apheresis on FABP4 serum levels in 64 high-risk patients (25 women, 39 men) under regular apheresis treatment. RESULTS: FABP4 levels were significantly reduced by 23.2 ± 1.8% by apheresis treatment. Although women had higher FABP4 levels than men (53.5 ± 8.3 ng/ml vs. 30.7 ± 4.3 ng/ml), reduction rate after lipoprotein apheresis was similar in both genders. Among the apheresis methods investigated, immunoadsorption of lipoproteins was most effective in lowering circulating FABP4. CONCLUSION: These data suggest that the reduction of FABP4 serum levels may contribute to the preventive effect of lipoprotein apheresis on cardiovascular events.

Tufted angioma with complete regression.

We describe 2 patients with tufted angioma (angioblastoma of Nakagawa) which regressed spontaneously. Both patients had a solitary but large lesion on the trunk. The 1st patient, a 3-month-old girl, presented with a 6-cm plaque which began to regress 2 years later. It regressed completely over 1 year and had not recurred after a further 6-year follow-up. The other patient, a 3-month-old boy, presented with a 12-cm mass of coalescent angiomatous papules which slowly regressed over 3-years, while small new lesions appeared in the adjacent contiguous skin. Eventually, gradual and near complete regression was observed after 8 years. The histology in both cases was typical, but bore some resemblance to the recently described kaposiform hemangioendothelioma, lobular capillary hemangioma and spindle cell hemangioendothelioma.

Genetic mediation of infanticide and parental behavior in male and female domestic and wild stock house mice.

Infanticide is a reproductive strategy found in many mammals, especially rodents. The proportion of male and female house mice (Mus domesticus) that are either infanticidal or noninfanticidal is strain specific and varies widely from stock to stock. Male house mice also show strain-specific variation in the behavioral mechanisms that inhibit infanticidal individuals from killing their own offspring. The adult offspring generated from reciprocally crossed CF-1 and Wild stock house mice were tested for their behavior toward newborn pups. In male CF-1 x Wild hybrids, the proportion of infanticidal and noninfanticidal males matched with their maternal phenotype, whereas female CF-1 x Wild hybrids exhibited a proportion of behaviors typical of the CF-1 phenotype, regardless of their mother's genotype. Our results suggest three conclusions: first, that infanticide is a highly labile and heritable behavior in both sexes; second, that there is a sex difference in the genetic substrate that regulates the inheritance of infanticidal behavior; and third, that selection pressures in male mice may operate independently on the mechanisms that promote spontaneous infanticidal behavior versus the mechanisms that inhibit infanticide.