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Circulation 26건

  1. [해외논문]   Promoting Risk Identification and Reduction of Cardiovascular Disease in Women Through Collaboration With Obstetricians and Gynecologists: A Presidential Advisory From the American Heart Association and the American College of Obstetricians and Gynecologists   SCI SCIE

    Brown, Haywood L. , Warner, John J. , Gianos, Eugenia , Gulati, Martha , Hill, Alexandria J. , Hollier, Lisa M. , Rosen, Stacey E. , Rosser, Mary L. , Wenger, Nanette K.
    Circulation v.137 no.24 ,pp. e843 - e852 , 2018 , 0009-7322 ,

    초록

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  2. [해외논문]   Conceptual Framework for Addressing Residual Atherosclerotic Cardiovascular Disease Risk in the Era of Precision Medicine   SCI SCIE

    Patel, Kershaw V. (Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas. ) , Pandey, Ambarish (Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas. ) , de Lemos, James A. (Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas.)
    Circulation v.137 no.24 ,pp. 2551 - 2553 , 2018 , 0009-7322 ,

    초록

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  3. [해외논문]   Genetic Risk Stratification : Tipping Point for Global Primary Prevention of Coronary Artery Disease   SCI SCIE

    Roberts, Robert (Department of Medicine, University of Arizona College of Medicine–Phoenix, International Society of Cardiovascular Translational Research.)
    Circulation v.137 no.24 ,pp. 2554 - 2556 , 2018 , 0009-7322 ,

    초록

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  4. [해외논문]   Hemodynamic and Echocardiographic Comparison of the Lotus and CoreValve Transcatheter Aortic Valves in Patients With High and Extreme Surgical Risk : An Analysis From the REPRISE III Randomized Controlled Trial   SCI SCIE

    Asch, Federico M. (MedStar Health Research Institute, Washington, DC (F.M.A., N.J.W.). ) , Vannan, Mani A. (Piedmont Marcus Heart Valve Center, Piedmont Heart Institute, Atlanta, GA (M.A.V.) ) , Singh, Siddharth (Cedars-Sinai Medical Center, Los Angeles, CA (S.S.). ) , Khandheria, Bijoy (Aurora St. Luke's Medical Center, Milwaukee, WI (B.K.). ) , Little, Stephen H. (Houston Methodist DeBakey Heart and Vascular Center, TX (S.H.L., M.J.R.). ) , Allocco, Dominic J. (Boston Scientific Corporation, Marlborough, MA (D.J.A., I.T.M.). ) , Meredith, Ian T. (Boston Scientific Corporation, Marlborough, MA (D.J.A., I.T.M.). ) , Feldman, Ted E. (Evanston Hospital Cardiology Division, Northshore University Health System, IL (T.E.F.). ) , Reardon, Michael J. (Houston Methodist DeBakey Heart and Vascular Center, TX (S.H.L., M.J.R.). ) , Weissman, Neil J. (MedStar Health Research Institute, Washington, DC (F.M.A., N.J.W.).)
    Circulation v.137 no.24 ,pp. 2557 - 2567 , 2018 , 0009-7322 ,

    초록

    Background: Comparative echocardiographic data on transcatheter aortic valve replacement systems from randomized trials are limited. The REPRISE III trial (Repositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve System – Randomized Clinical Evaluation) is a multicenter, randomized comparison of a mechanically expanded (Lotus) versus self-expanding (CoreValve) transcatheter aortic valve replacement device. This analysis rigorously assesses Doppler-derived valve hemodynamics and the impact on outcomes at 1 year in patients with extreme/high surgical risk treated with Lotus and CoreValve from REPRISE III. Methods: REPRISE III includes patients with extreme- and high-risk aortic stenosis. Patients were enrolled at 55 centers. All transthoracic echocardiograms with Doppler were obtained following a standard protocol up to 12 months postimplant and analyzed by a core laboratory. Valve size, mean gradient, aortic valve area, and Doppler velocity index and their impact on clinical outcomes are reported. Additional parameters including paravalvular leak were evaluated using a multiparametric approach. Results: A total of 912 patients were randomly assigned (2:1 ratio; 607 Lotus:305 CoreValve). Median age was 84 years, 51% of the patients were women, and the Society of Thoracic Surgeons score was 6.8±4.1. CoreValve demonstrated lower gradients and larger aortic valve area and Doppler velocity index than Lotus at discharge; the difference decreased in subsequent follow-up up to a year (all P <0.01). Lotus had lower rates of paravalvular leak that persisted over time ( P <0.05). Similar outcomes were seen when comparing each valve type by size group (small, medium, large). The hemodynamic differences between valves did not translate into worse clinical outcomes. All-cause mortality was not different between the 2 groups in any of the 3 valve sizes. When comparing patients with normal valve gradients (<20 mm Hg, n=780) with those with abnormal gradients (>20 mm Hg, n=48) in the entire patient population, all-cause mortality was not different. This was also not significant when evaluating each valve type separately. Similarly, there were no differences for aortic valve area >1.1 cm 2 or <1.1 cm 2 and for Doppler velocity index >0.35 or <0.35 (all P = not significant). Conclusions: Lotus had significantly greater freedom from moderate or severe paravalvular leak and smaller valve area and higher gradients than CoreValve. The hemodynamic differences were not associated with any clinical differences in the composite end point of mortality, disabling stroke, and moderate paravalvular leak or with quality of life at 1 year of follow-up. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02202434.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  5. [해외논문]   The Lotus Valve : Can It Float Above the Muddy Waters?   SCI SCIE

    Hahn, Rebecca T. (Columbia University Medical Center, New York Presbyterian Hospital.)
    Circulation v.137 no.24 ,pp. 2568 - 2571 , 2018 , 0009-7322 ,

    초록

    Background: Comparative echocardiographic data on transcatheter aortic valve replacement systems from randomized trials are limited. The REPRISE III trial (Repositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve System – Randomized Clinical Evaluation) is a multicenter, randomized comparison of a mechanically expanded (Lotus) versus self-expanding (CoreValve) transcatheter aortic valve replacement device. This analysis rigorously assesses Doppler-derived valve hemodynamics and the impact on outcomes at 1 year in patients with extreme/high surgical risk treated with Lotus and CoreValve from REPRISE III. Methods: REPRISE III includes patients with extreme- and high-risk aortic stenosis. Patients were enrolled at 55 centers. All transthoracic echocardiograms with Doppler were obtained following a standard protocol up to 12 months postimplant and analyzed by a core laboratory. Valve size, mean gradient, aortic valve area, and Doppler velocity index and their impact on clinical outcomes are reported. Additional parameters including paravalvular leak were evaluated using a multiparametric approach. Results: A total of 912 patients were randomly assigned (2:1 ratio; 607 Lotus:305 CoreValve). Median age was 84 years, 51% of the patients were women, and the Society of Thoracic Surgeons score was 6.8±4.1. CoreValve demonstrated lower gradients and larger aortic valve area and Doppler velocity index than Lotus at discharge; the difference decreased in subsequent follow-up up to a year (all P <0.01). Lotus had lower rates of paravalvular leak that persisted over time ( P <0.05). Similar outcomes were seen when comparing each valve type by size group (small, medium, large). The hemodynamic differences between valves did not translate into worse clinical outcomes. All-cause mortality was not different between the 2 groups in any of the 3 valve sizes. When comparing patients with normal valve gradients (<20 mm Hg, n=780) with those with abnormal gradients (>20 mm Hg, n=48) in the entire patient population, all-cause mortality was not different. This was also not significant when evaluating each valve type separately. Similarly, there were no differences for aortic valve area >1.1 cm 2 or <1.1 cm 2 and for Doppler velocity index >0.35 or <0.35 (all P = not significant). Conclusions: Lotus had significantly greater freedom from moderate or severe paravalvular leak and smaller valve area and higher gradients than CoreValve. The hemodynamic differences were not associated with any clinical differences in the composite end point of mortality, disabling stroke, and moderate paravalvular leak or with quality of life at 1 year of follow-up. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02202434.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  6. [해외논문]   Cigarette Smoking and Incident Heart Failure : Insights From the Jackson Heart Study   SCI SCIE

    Kamimura, Daisuke (Department of Medicine (D.K., E.R.F., J.B., M.D.W., A.C., M.E.H.) ) , Cain, Loretta R. (Department of Data Sciences (L.R.C.), University of Mississippi Medical Center, Jackson. ) , Mentz, Robert J. (Department of Medicine, Division of Cardiology, Duke University School of Medicine, Durham, NC (R.J.M.). ) , White, Wendy B. (Tougaloo College, MS (W.B.W.). ) , Blaha, Michael J. (Ciccarone Center for the Prevention of Heart Disease and Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD (M.J.B.). ) , DeFilippis, Andrew P. (Division of Cardiovascular Medicine, University of Louisville, KY (A.P.D., A.B.). ) , Fox, Ervin R. (Department of Medicine (D.K., E.R.F., J.B., M.D.W., A.C., M.E.H.) ) , Rodriguez, Carlos J. (Department of Medicine and Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (C.J.R.). ) , Keith, Rachel J. (Diabetes and Obesity Center, University of Louisville School of Medicine, KY (R.J.K., A.B.). ) , Benjamin, Emelia J. (Department of Medicine, Boston University School of Medicine and Department of Epidemiology, Boston University School of Public Health, MA (E.J.B.). ) , Butler, Javed (Department of Medicin) , Bhatnagar, Aruni , Robertson, Rose M. , Winniford, Michael D. , Correa, Adolfo , Hall, Michael E.
    Circulation v.137 no.24 ,pp. 2572 - 2582 , 2018 , 0009-7322 ,

    초록

    Background: Cigarette smoking has been linked with several factors associated with cardiac dysfunction. We hypothesized that cigarette smoking is associated with left ventricular (LV) structure and function, and incident heart failure (HF) hospitalization. Methods: We investigated 4129 (never smoker n=2884, current smoker n=503, and former smoker n=742) black participants (mean age, 54 years; 63% women) without a history of HF or coronary heart disease at baseline in the Jackson Heart Study. We examined the relationships between cigarette smoking and LV structure and function by using cardiac magnetic resonance imaging among 1092 participants, cigarette smoking and brain natriuretic peptide levels among 3325 participants, and incident HF hospitalization among 3633 participants with complete data. Results: After adjustment for confounding factors, current smoking was associated with higher mean LV mass index and lower mean LV circumferential strain ( P <0.05, for both) in comparison with never smoking. Smoking status, intensity, and burden were associated with higher mean brain natriuretic peptide levels (all P <0.05). Over 8.0 years (7.7–8.0) median follow-up, there were 147 incident HF hospitalizations. After adjustment for traditional risk factors and incident coronary heart disease, current smoking (hazard ratio, 2.82; 95% confidence interval, 1.71–4.64), smoking intensity among current smokers (≥20 cigarettes/d: hazard ratio, 3.48; 95% confidence interval, 1.65–7.32), and smoking burden among ever smokers (≥15 pack-years: hazard ratio, 2.06; 95% confidence interval, 1.29–3.3) were significantly associated with incident HF hospitalization in comparison with never smoking. Conclusions: In blacks, cigarette smoking is an important risk factor for LV hypertrophy, systolic dysfunction, and incident HF hospitalization even after adjusting for effects on coronary heart disease.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  7. [해외논문]   Associations of Fitness, Physical Activity, Strength, and Genetic Risk With Cardiovascular Disease : Longitudinal Analyses in the UK Biobank Study   SCI SCIE

    Tikkanen, Emmi (Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (E.I., E.T.). ) , Gustafsson, Stefan (Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Sweden (S.G.). ) , Ingelsson, Erik (Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (E.I., E.T.).)
    Circulation v.137 no.24 ,pp. 2583 - 2591 , 2018 , 0009-7322 ,

    초록

    Background: Observational studies have shown inverse associations among fitness, physical activity, and cardiovascular disease. However, little is known about these associations in individuals with elevated genetic susceptibility for these diseases. Methods: We estimated associations of grip strength, objective and subjective physical activity, and cardiorespiratory fitness with cardiovascular events and all-cause death in a large cohort of 502 635 individuals from the UK Biobank (median follow-up, 6.1 years; interquartile range, 5.4–6.8 years). Then we further examined these associations in individuals with different genetic burden by stratifying individuals based on their genetic risk scores for coronary heart disease and atrial fibrillation. We compared disease risk among individuals in different tertiles of fitness, physical activity, and genetic risk using lowest tertiles as reference. Results: Grip strength, physical activity, and cardiorespiratory fitness showed inverse associations with incident cardiovascular events (coronary heart disease: hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.77–0.81; HR, 0.95; 95% CI, 0.93–0.97; and HR, 0.68; 95% CI, 0.63–0.74, per SD change, respectively; atrial fibrillation: HR, 0.75; 95% CI, 0.73–0.76; HR, 0.93; 95% CI, 0.91–0.95; and HR, 0.60; 95% CI, 0.56–0.65, per SD change, respectively). Higher grip strength and cardiorespiratory fitness were associated with lower risk of incident coronary heart disease and atrial fibrillation in each genetic risk score group ( P trend <0.001 in each genetic risk category). In particular, high levels of cardiorespiratory fitness were associated with 49% lower risk for coronary heart disease (HR, 0.51; 95% CI, 0.38–0.69) and 60% lower risk for atrial fibrillation (HR, 0.40; 95%, CI 0.30–0.55) among individuals at high genetic risk for these diseases. Conclusions: Fitness and physical activity demonstrated inverse associations with incident cardiovascular disease in the general population, as well as in individuals with elevated genetic risk for these diseases.

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    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  8. [해외논문]   Inhibition of Endothelial Notch Signaling Impairs Fatty Acid Transport and Leads to Metabolic and Vascular Remodeling of the Adult Heart   SCI SCIE

    Jabs, Markus (Division Vascular Signaling and Cancer (M.J., J.T., I.M., S.E.H., E.-M.W., A.F.) ) , Rose, Adam J. (Joint Division Molecular Metabolic Control, German Cancer Research Center, Heidelberg, Center for Molecular Biology, and University Hospital Heidelberg, Germany (A.J.R., T.P.S.). ) , Lehmann, Lorenz H. (Department of Molecular Cardiology and Epigenetics (L.H.L., J.B.) ) , Taylor, Jacqueline (Division Vascular Signaling and Cancer (M.J., J.T., I.M., S.E.H., E.-M.W., A.F.) ) , Moll, Iris (Division Vascular Signaling and Cancer (M.J., J.T., I.M., S.E.H., E.-M.W., A.F.) ) , Sijmonsma, Tjeerd P. (Joint Division Molecular Metabolic Control, German Cancer Research Center, Heidelberg, Center for Molecular Biology, and University Hospital Heidelberg, Germany (A.J.R., T.P.S.). ) , Herberich, Stefanie E. (Division Vascular Signaling and Cancer (M.J., J.T., I.M., S.E.H., E.-M.W., A.F.) ) , Sauer, Sven W. (Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Germany (S.W.S., J.G.O.). ) , Poschet, Gernot (Center for Organismal Studies (G.P., R.H.) ) , Federico, Giuseppina (Division Cellular and Molecular Pathology (G) , Mogler, Carolin , Weis, Eva-Maria , Augustin, Hellmut G. , Yan, Minhong , Gretz, Norbert , Schmid, Roland M. , Adams, Ralf H. , Grö , ne, Hermann-Joseph , Hell, Rü , diger , Okun, Jü , rgen G. , Backs, Johannes , Nawroth, Peter P. , Herzig, Stephan , Fischer, Andreas
    Circulation v.137 no.24 ,pp. 2592 - 2608 , 2018 , 0009-7322 ,

    초록

    Background: Nutrients are transported through endothelial cells before being metabolized in muscle cells. However, little is known about the regulation of endothelial transport processes. Notch signaling is a critical regulator of metabolism and angiogenesis during development. Here, we studied how genetic and pharmacological manipulation of endothelial Notch signaling in adult mice affects endothelial fatty acid transport, cardiac angiogenesis, and heart function. Methods: Endothelial-specific Notch inhibition was achieved by conditional genetic inactivation of Rbp-jκ in adult mice to analyze fatty acid metabolism and heart function. Wild-type mice were treated with neutralizing antibodies against the Notch ligand Delta-like 4. Fatty acid transport was studied in cultured endothelial cells and transgenic mice. Results: Treatment of wild-type mice with Delta-like 4 neutralizing antibodies for 8 weeks impaired fractional shortening and ejection fraction in the majority of mice. Inhibition of Notch signaling specifically in the endothelium of adult mice by genetic ablation of Rbp-jκ caused heart hypertrophy and failure. Impaired heart function was preceded by alterations in fatty acid metabolism and an increase in cardiac blood vessel density. Endothelial Notch signaling controlled the expression of endothelial lipase, Angptl4, CD36, and Fabp4, which are all needed for fatty acid transport across the vessel wall. In endothelial-specific Rbp-jκ–mutant mice, lipase activity and transendothelial transport of long-chain fatty acids to muscle cells were impaired. In turn, lipids accumulated in the plasma and liver. The attenuated supply of cardiomyocytes with long-chain fatty acids was accompanied by higher glucose uptake, increased concentration of glycolysis intermediates, and mTOR-S6K signaling. Treatment with the mTOR inhibitor rapamycin or displacing glucose as cardiac substrate by feeding a ketogenic diet prolonged the survival of endothelial-specific Rbp-jκ–deficient mice. Conclusions: This study identifies Notch signaling as a novel regulator of fatty acid transport across the endothelium and as an essential repressor of angiogenesis in the adult heart. The data imply that the endothelium controls cardiomyocyte metabolism and function.

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    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  9. [해외논문]   Top-NOTCH Regulation of Cardiac Metabolism   SCI SCIE

    Lim, Radiance (Angiogenesis & Metabolism Laboratory, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (R.L., M.P.). ) , Potente, Michael (Angiogenesis & Metabolism Laboratory, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (R.L., M.P.).)
    Circulation v.137 no.24 ,pp. 2609 - 2612 , 2018 , 0009-7322 ,

    초록

    Background: Nutrients are transported through endothelial cells before being metabolized in muscle cells. However, little is known about the regulation of endothelial transport processes. Notch signaling is a critical regulator of metabolism and angiogenesis during development. Here, we studied how genetic and pharmacological manipulation of endothelial Notch signaling in adult mice affects endothelial fatty acid transport, cardiac angiogenesis, and heart function. Methods: Endothelial-specific Notch inhibition was achieved by conditional genetic inactivation of Rbp-jκ in adult mice to analyze fatty acid metabolism and heart function. Wild-type mice were treated with neutralizing antibodies against the Notch ligand Delta-like 4. Fatty acid transport was studied in cultured endothelial cells and transgenic mice. Results: Treatment of wild-type mice with Delta-like 4 neutralizing antibodies for 8 weeks impaired fractional shortening and ejection fraction in the majority of mice. Inhibition of Notch signaling specifically in the endothelium of adult mice by genetic ablation of Rbp-jκ caused heart hypertrophy and failure. Impaired heart function was preceded by alterations in fatty acid metabolism and an increase in cardiac blood vessel density. Endothelial Notch signaling controlled the expression of endothelial lipase, Angptl4, CD36, and Fabp4, which are all needed for fatty acid transport across the vessel wall. In endothelial-specific Rbp-jκ–mutant mice, lipase activity and transendothelial transport of long-chain fatty acids to muscle cells were impaired. In turn, lipids accumulated in the plasma and liver. The attenuated supply of cardiomyocytes with long-chain fatty acids was accompanied by higher glucose uptake, increased concentration of glycolysis intermediates, and mTOR-S6K signaling. Treatment with the mTOR inhibitor rapamycin or displacing glucose as cardiac substrate by feeding a ketogenic diet prolonged the survival of endothelial-specific Rbp-jκ–deficient mice. Conclusions: This study identifies Notch signaling as a novel regulator of fatty acid transport across the endothelium and as an essential repressor of angiogenesis in the adult heart. The data imply that the endothelium controls cardiomyocyte metabolism and function.

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  10. [해외논문]   Cytosolic DNA Sensing Promotes Macrophage Transformation and Governs Myocardial Ischemic Injury   SCI SCIE

    Cao, Dian J. (Departments of Internal Medicine (Cardiology) (D.C., G.G.S., E.V., N.J., H.I.M., T.G.G., J.A.H.) ) , Schiattarella, Gabriele G. (Departments of Internal Medicine (Cardiology) (D.C., G.G.S., E.V., N.J., H.I.M., T.G.G., J.A.H.) ) , Villalobos, Elisa (Departments of Internal Medicine (Cardiology) (D.C., G.G.S., E.V., N.J., H.I.M., T.G.G., J.A.H.) ) , Jiang, Nan (Departments of Internal Medicine (Cardiology) (D.C., G.G.S., E.V., N.J., H.I.M., T.G.G., J.A.H.) ) , May, Herman I. (Departments of Internal Medicine (Cardiology) (D.C., G.G.S., E.V., N.J., H.I.M., T.G.G., J.A.H.) ) , Li, Tuo (Molecular Biology (T.L., Z.J.C., J.A.H.) ) , Chen, Zhijian J. (Molecular Biology (T.L., Z.J.C., J.A.H.) ) , Gillette, Thomas G. (Departments of Internal Medicine (Cardiology) (D.C., G.G.S., E.V., N.J., H.I.M., T.G.G., J.A.H.) ) , Hill, Joseph A. (Departments of Internal Medicine (Cardiology) (D.C., G.G.S., E.V., N.J., H.I.M., T.G.G., J.A.H.))
    Circulation v.137 no.24 ,pp. 2613 - 2634 , 2018 , 0009-7322 ,

    초록

    Background: Myocardium irreversibly injured by ischemic stress must be efficiently repaired to maintain tissue integrity and contractile performance. Macrophages play critical roles in this process. These cells transform across a spectrum of phenotypes to accomplish diverse functions ranging from mediating the initial inflammatory responses that clear damaged tissue to subsequent reparative functions that help rebuild replacement tissue. Although macrophage transformation is crucial to myocardial repair, events governing this transformation are poorly understood. Methods: Here, we set out to determine whether innate immune responses triggered by cytoplasmic DNA play a role. Results: We report that ischemic myocardial injury, along with the resulting release of nucleic acids, activates the recently described cyclic GMP-AMP synthase–stimulator of interferon genes pathway. Animals lacking cyclic GMP-AMP synthase display significantly improved early survival after myocardial infarction and diminished pathological remodeling, including ventricular rupture, enhanced angiogenesis, and preserved ventricular contractile function. Furthermore, cyclic GMP-AMP synthase loss of function abolishes the induction of key inflammatory programs such as inducible nitric oxide synthase and promotes the transformation of macrophages to a reparative phenotype, which results in enhanced repair and improved hemodynamic performance. Conclusions: These results reveal, for the first time, that the cytosolic DNA receptor cyclic GMP-AMP synthase functions during cardiac ischemia as a pattern recognition receptor in the sterile immune response. Furthermore, we report that this pathway governs macrophage transformation, thereby regulating postinjury cardiac repair. Because modulators of this pathway are currently in clinical use, our findings raise the prospect of new treatment options to combat ischemic heart disease and its progression to heart failure.

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