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The role and modulation of autophagy in experimental models of myocardial ischemia-reperfusion injury

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Journal of Geriatric Cardiology 2014年第4期11卷 338-348页

作者： Carol Chen-Scarabelli Pratik R. Agrawal Louis Saravolatz Cadigia Abuniat Gabriele Scarabelli Anastasis Stephanou Leena Loomba jagat narula Tiziano M. Scarabelli Richard Knight VA Ann Arbor Health Care System University of Michigan 2215 Fuller Rd Ann Arbor M148105 USA Zena and Michael A. Wiener Cardiovascular Institute Mount Sinai Medical Center One Gustave L. Levy Place Box 1030 New York NY 10029-6574 USA St John Hospital and Medical Center Wayne State University School of Medicine 22101 Moross Rd. Detroit M148236 USA Medical and Molecular Biology Unit University College London UCL 30 Guildford St. London WC1N 1EH UK

A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion （I/R） injury. This tightly orchestrated cata-bolic cellular‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protec-tive mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the va-riability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin （mTOR） inhibitors, adenosine monophosphate-activated protein kinase （AMPK） modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic ma-nipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.

关键词： Autophagy Heart Ischemia-reperfusion injury Cell survival

Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease

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Journal of Geriatric Cardiology 2016年第8期13卷 701-711页

作者： Giovanni Corsetti Evasio Pasini Tiziano M Scarabelli Claudia Romano Pratik R Agrawal Carol Chen-Scarabelli Richard Knight Louis Saravolatz jagat narula Mario Ferrari-Vivaldi Vincenzo Flati Deodato Assanelli Francesco S Dioguardi Department of Clinical & Experimental Sciences Division of Human Anatomy & Physiopathology University of Brescia Brescia Italy 'S.Maugeri Foundation ' IRCCS Cardiology Division Medical Centre of Lumezzane Brescia Italy Zena and Michael A Wiener Cardiovascular Institute Mount Sinai Medical Center New York USA Center for Heart and Vessel Preclinical Studies St. John Hospital & Medical Center Wayne State University School of Medicine Detroit USA VA Ann Arbor Health Care System University of Michigan Ann Arbor USA Department of Cardiovascular Surgery 'San Rocco' Hospital Ome Brescia Italy Department of Biotechnological and Applied Clinical Sciences University of L 'Aquila L 'Aquila Italy Division of Sport-Internal Medicine Department of Clinical & Experimental Sciences University of Brescia Brescia Italy Department of Clinical Sciences and Community Health University of Milan Milan Italy

Background Klotho proteins （α- and β） are membrane-based circulating proteins that regulate cell metabolism, as well as the lifespan modulating activity of Fibroblast Growth Factors （FGFs）. Recent data has shown that higher plasma circulating Klotho levels reduce cardio- vascular risk, suggesting Klotho has a protective role in cardiovascular diseases. However, although so far it has been identified in various organs, it is unknown whether cardiomyocytes express Klotho and FGFs, and whether high cardiovascular risk could affect cardiac expres- sion ofKlotho, FGFs and other molecules. Methods We selected 20 patients with an estimated 10-year high atherosclerotic cardiovascular disease and 10 age-matched control subjects with an estimated 10-year low risk undergone cardiac surgery for reasons other than coronary artery by-pass. In myocardial biopsies, we evaluated by immuno-histochemistry whether Klotho and FGFs were expressed in cardiomyo- cytes, and whether higher cardiovascular risk influenced the expression of other molecules involved in endoplasmic reticulum stress, oxida- tive stress, inflammation and fibrosis. Results Only cardiomyocytes of patients with a higher cardiovascular risk showed lower expression of Klotho, but higher expressions of FGFs. Furthermore, higher cardiovascular risk was associated with increased expression of oxidative and endoplasmic reticular stress, inflammation and fibrosis. Conclusions This study showed for the first time that Klotho proteins are ex- pressed in human cardiomyocytes and that cardiac expression of Klotho is down-regulated in higher cardiovascular risk patients, while expression of stress-related molecules were significantly increased.

关键词： Atherosclerotic disease Cardiomyocytes Cardiovascular risk Human heart Klotho

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心脏结节病的影像学进展

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中华核医学与分子影像杂志 2020年第2期40卷 122-128页

作者：孙若西(译) 汪蕾方纬(审校) 北京协和医学院、中国医学科学院阜外医院核医学科 100037

结节病是一种病因不明的具有非干酪样肉芽肿特征的慢性疾病。结节病的心脏受累可导致多种严重后果,如高度心脏传导阻滞、心律失常、心肌病,甚至死亡。心脏结节病可发生在已确诊结节病的患者中,也可能是疾病的唯一表现。传统的诊断技术(... 详细信息

结节病是一种病因不明的具有非干酪样肉芽肿特征的慢性疾病。结节病的心脏受累可导致多种严重后果,如高度心脏传导阻滞、心律失常、心肌病,甚至死亡。心脏结节病可发生在已确诊结节病的患者中,也可能是疾病的唯一表现。传统的诊断技术(包括超声心动图)诊断心脏结节病的灵敏度较低。越来越多的证据表明,先进心脏影像学技术(如MRI、PET)在心脏结节病的诊断、危险分层以及患者管理中具有重要价值。本综述重点强调了心脏影像学技术在评估疑似或确诊心脏结节病患者中的相关重要理论知识和实践意义。

关键词： MRI PET 心律失常心脏结节病心肌病心脏传导阻滞