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  1. Article ; Online: Evaluation of long-chain fatty acid respiration in neonatal mouse cardiomyocytes using SeaHorse instrument

    Aude Angelini / Xinchun Pi / Liang Xie

    STAR Protocols, Vol 3, Iss 2, Pp 101392- (2022)

    2022  

    Abstract: Summary: Metabolic switches play a critical role in the pathophysiology of cardiac diseases, including heart failure. Here, we describe an assay for long-chain fatty acid oxidation in neonatal mouse cardiomyocytes by using a SeaHorse Flux Analyzer ( ... ...

    Abstract Summary: Metabolic switches play a critical role in the pathophysiology of cardiac diseases, including heart failure. Here, we describe an assay for long-chain fatty acid oxidation in neonatal mouse cardiomyocytes by using a SeaHorse Flux Analyzer (Agilent). This protocol is a simplified but robust adaptation of the standard protocol that enables metabolic measurements in cells isolated from transgenic mouse models, which can be timesaving and informative. Cell isolation and culture represent a critical point that may require bench optimization.For complete details on the use and execution of this protocol, please refer to Angelini et al. (2021). : Publisher's note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
    Keywords Cell Biology ; Cell culture ; Cell isolation ; Metabolism ; Protein Biochemistry ; Science (General) ; Q1-390
    Subject code 571
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: PHDs/CPT1B/VDAC1 axis regulates long-chain fatty acid oxidation in cardiomyocytes

    Aude Angelini / Pradip K. Saha / Antrix Jain / Sung Yun Jung / Randall L. Mynatt / Xinchun Pi / Liang Xie

    Cell Reports, Vol 37, Iss 1, Pp 109767- (2021)

    2021  

    Abstract: Summary: Cardiac metabolism is a high-oxygen-consuming process, showing a preference for long-chain fatty acid (LCFA) as the fuel source under physiological conditions. However, a metabolic switch (favoring glucose instead of LCFA) is commonly reported ... ...

    Abstract Summary: Cardiac metabolism is a high-oxygen-consuming process, showing a preference for long-chain fatty acid (LCFA) as the fuel source under physiological conditions. However, a metabolic switch (favoring glucose instead of LCFA) is commonly reported in ischemic or late-stage failing hearts. The mechanism regulating this metabolic switch remains poorly understood. Here, we report that loss of PHD2/3, the cellular oxygen sensors, blocks LCFA mitochondria uptake and β-oxidation in cardiomyocytes. In high-fat-fed mice, PHD2/3 deficiency improves glucose metabolism but exacerbates the cardiac defects. Mechanistically, we find that PHD2/3 bind to CPT1B, a key enzyme of mitochondrial LCFA uptake, promoting CPT1B-P295 hydroxylation. Further, we show that CPT1B-P295 hydroxylation is indispensable for its interaction with VDAC1 and LCFA β-oxidation. Finally, we demonstrate that a CPT1B-P295A mutant constitutively binds to VDAC1 and rescues LCFA metabolism in PHD2/3-deficient cardiomyocytes. Together, our data identify an oxygen-sensitive regulatory axis involved in cardiac metabolism.
    Keywords cardiac metabolism switch ; carnitine O-palmitoyltransferase 1b ; myocardial infarction ; heart failure ; hypoxia ; long-chain fatty acid ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Endothelium-specific depletion of LRP1 improves glucose homeostasis through inducing osteocalcin

    Hua Mao / Luge Li / Qiying Fan / Aude Angelini / Pradip K. Saha / Cristian Coarfa / Kimal Rajapakshe / Dimuthu Perera / Jizhong Cheng / Huaizhu Wu / Christie M. Ballantyne / Zheng Sun / Liang Xie / Xinchun Pi

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 12

    Abstract: The vascular endothelium contributes to metabolic regulation, however, the underlying mechanisms are not fully understood. Here the authors show that endothelial low-density lipoprotein receptor-related protein 1 regulates glucose homeostasis via ... ...

    Abstract The vascular endothelium contributes to metabolic regulation, however, the underlying mechanisms are not fully understood. Here the authors show that endothelial low-density lipoprotein receptor-related protein 1 regulates glucose homeostasis via osteocalcin expression.
    Keywords Science ; Q
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Loss of bone morphogenetic protein-binding endothelial regulator causes insulin resistance

    Hua Mao / Luge Li / Qiying Fan / Aude Angelini / Pradip K. Saha / Huaizhu Wu / Christie M. Ballantyne / Sean M. Hartig / Liang Xie / Xinchun Pi

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 10

    Abstract: Type 2 diabetes is associated with chronic inflammation and is characterized by insulin resistance. Here, the authors identify a crucial role for endothelial BMPER function in glucose homeostasis, and BMPER overexpression was shown to alleviate insulin ... ...

    Abstract Type 2 diabetes is associated with chronic inflammation and is characterized by insulin resistance. Here, the authors identify a crucial role for endothelial BMPER function in glucose homeostasis, and BMPER overexpression was shown to alleviate insulin resistance and hyperglycemia in diabetic mice.
    Keywords Science ; Q
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Correction

    Laura Dyer / Pamela Lockyer / Yaxu Wu / Arnab Saha / Chelsea Cyr / Martin Moser / Xinchun Pi / Cam Patterson

    PLoS ONE, Vol 13, Iss 11, p e

    BMPER Promotes Epithelial-Mesenchymal Transition in the Developing Cardiac Cushions.

    2018  Volume 0207504

    Abstract: This corrects the article DOI:10.1371/journal.pone.0139209.]. ...

    Abstract [This corrects the article DOI:10.1371/journal.pone.0139209.].
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Endothelial LRP1 regulates metabolic responses by acting as a co-activator of PPARγ

    Hua Mao / Pamela Lockyer / Luge Li / Christie M. Ballantyne / Cam Patterson / Liang Xie / Xinchun Pi

    Nature Communications, Vol 8, Iss 1, Pp 1-

    2017  Volume 11

    Abstract: LDL receptor-related protein 1 (LRP1) is an endocytic receptor involved in cell signalling and energy homeostasis. Here Maoet al. demonstrate that endothelial Lrp1 modulates lipid and glucose metabolism by binding the nuclear receptor Pparγ and promoting ...

    Abstract LDL receptor-related protein 1 (LRP1) is an endocytic receptor involved in cell signalling and energy homeostasis. Here Maoet al. demonstrate that endothelial Lrp1 modulates lipid and glucose metabolism by binding the nuclear receptor Pparγ and promoting its transcriptional activity.
    Keywords Science ; Q
    Language English
    Publishing date 2017-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: BMPER Promotes Epithelial-Mesenchymal Transition in the Developing Cardiac Cushions.

    Laura Dyer / Pamela Lockyer / Yaxu Wu / Arnab Saha / Chelsea Cyr / Martin Moser / Xinchun Pi / Cam Patterson

    PLoS ONE, Vol 10, Iss 9, p e

    2015  Volume 0139209

    Abstract: Formation of the cardiac valves is an essential component of cardiovascular development. Consistent with the role of the bone morphogenetic protein (BMP) signaling pathway in cardiac valve formation, embryos that are deficient for the BMP regulator BMPER ...

    Abstract Formation of the cardiac valves is an essential component of cardiovascular development. Consistent with the role of the bone morphogenetic protein (BMP) signaling pathway in cardiac valve formation, embryos that are deficient for the BMP regulator BMPER (BMP-binding endothelial regulator) display the cardiac valve anomaly mitral valve prolapse. However, how BMPER deficiency leads to this defect is unknown. Based on its expression pattern in the developing cardiac cushions, we hypothesized that BMPER regulates BMP2-mediated signaling, leading to fine-tuned epithelial-mesenchymal transition (EMT) and extracellular matrix deposition. In the BMPER-/- embryo, EMT is dysregulated in the atrioventricular and outflow tract cushions compared with their wild-type counterparts, as indicated by a significant increase of Sox9-positive cells during cushion formation. However, proliferation is not impaired in the developing BMPER-/- valves. In vitro data show that BMPER directly binds BMP2. In cultured endothelial cells, BMPER blocks BMP2-induced Smad activation in a dose-dependent manner. In addition, BMP2 increases the Sox9 protein level, and this increase is inhibited by co-treatment with BMPER. Consistently, in the BMPER-/- embryos, semi-quantitative analysis of Smad activation shows that the canonical BMP pathway is significantly more active in the atrioventricular cushions during EMT. These results indicate that BMPER negatively regulates BMP-induced Smad and Sox9 activity during valve development. Together, these results identify BMPER as a regulator of BMP2-induced cardiac valve development and will contribute to our understanding of valvular defects.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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