Abstract：
:The benefits of physical activity in cardiovascular diseases have long been appreciated. However, the molecular mechanisms that trigger and sustain the cardiac benefits of exercise are poorly understood, and it is anticipated that unveiling these mechanisms will identify novel therapeutic targets. In search of these mechanisms we took advantage of unbiased RNA-sequencing (RNA-seq) technology to discover cardiac gene targets whose expression is disrupted in heart failure (HF) and rescued by exercise in a rat model. Upon exhaustive validation in a separate rat cohort (qPCR) and human datasets, we shortlisted 16 targets for a cell-based screening, aiming to evaluate whether targeted disruption of these genes with silencing RNA would affect the abundance of a CVD biomarker (BNP, B-type natriuretic peptide) in human cardiomyocytes. Overall, these experiments showed that Proline Dehydrogenase (PRODH) expression is reduced in human failing hearts, rescued by exercise in a rat model of HF, and its targeted knockdown increases BNP expression in human cardiomyocytes. On the other hand, overexpression of PRODH increases the abundance of metabolism-related gene transcripts, and PRODH appears to be crucial to sustain normal mitochondrial function and maintenance of ATP levels in human cardiomyocytes in a hypoxic environment, as well as for redox homeostasis in both normoxic and hypoxic conditions. Altogether our findings show that PRODH is a novel molecular target of exercise in failing hearts and highlight its role in cardiomyocyte physiology, thereby proposing PRODH as a potential experimental target for gene therapy in HF.
journal_name
Prog Cardiovasc Disjournal_title
Progress in cardiovascular diseasesauthors
Moreira JBN,Wohlwend M,Fenk S,Åmellem I,Flatberg A,Kraljevic J,Marinovic J,Ljubkovic M,Bjørkøy G,Wisløff Udoi
10.1016/j.pcad.2019.03.002subject
Has Abstractpub_date
2019-01-01 00:00:00pages
193-202issue
2eissn
0033-0620issn
1873-1740pii
S0033-0620(19)30047-7journal_volume
62pub_type
杂志文章,评审abstract：:Hypertension (HTN) is the most common chronic disease in the U.S., and the standard model of office-based care delivery has yielded suboptimal outcomes, with approximately 50% of affected patients not achieving blood pressure (BP) control. Poor population-level BP control has been primarily attributed to therapeutic i...
journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/j.pcad.2016.09.005
更新日期：2016-01-01 00:00:00
abstract：:The purpose of this article is to highlight approaches to increase movement, physical activity (PA), and cardiorespiratory fitness, and reduce sedentary behavior (SB) in the context of the workplace. A deliberate strategy that will enable the successful promotion of movement at the workplace includes a business plan a...
journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/j.pcad.2020.10.004
更新日期：2020-10-24 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/s0033-0620(98)80004-2
更新日期：1998-05-01 00:00:00
abstract：:Physicians who supervise stress-imaging procedures, whether they be stress nuclear or stress echocardiography tests, are increasingly required to incorporate important principles in the interpretation of the test results. Important guiding principles, common to these tests, are reviewed in this article. The principles...
journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章
doi：10.1053/pcad.2001.20501
更新日期：2001-01-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/0033-0620(82)90016-0
更新日期：1982-11-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/s0033-0620(96)80025-9
更新日期：1996-09-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/s0033-0620(03)00085-9
更新日期：2003-09-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/j.pcad.2019.10.001
更新日期：2019-01-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 历史文章,杂志文章
doi：10.1016/j.pcad.2010.01.001
更新日期：2010-07-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/j.pcad.2015.04.003
更新日期：2015-07-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章
doi：10.1016/j.pcad.2013.09.019
更新日期：2013-11-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/j.pcad.2017.02.002
更新日期：2017-01-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/j.pcad.2010.02.003
更新日期：2010-05-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1016/s0033-0620(96)80029-6
更新日期：1996-03-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/0033-0620(83)90008-7
更新日期：1983-11-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/s0033-0620(03)00077-x
更新日期：2003-07-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章
doi：10.1016/j.pcad.2017.08.005
更新日期：2017-01-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/s0033-0620(99)70022-8
更新日期：1999-05-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/j.pcad.2013.01.003
更新日期：2013-03-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/j.pcad.2019.02.002
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/j.pcad.2008.08.007
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/j.pcad.2015.07.006
更新日期：2015-11-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/j.pcad.2010.07.004
更新日期：2010-11-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
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更新日期：2017-01-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/j.pcad.2019.11.016
更新日期：2019-01-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/j.pcad.2017.11.008
更新日期：2017-01-01 00:00:00
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journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
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更新日期：1988-03-01 00:00:00
abstract：:Telecardiology holds great promise for Africa, from tele-echocardiography and tele-ECG s, to home monitoring and text messaging for medication adherence monitoring. The burden of disease is great and there is an extreme shortage of health professionals. Telemedicine can provide access to scarce specialist care, improv...
journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
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更新日期：2013-11-01 00:00:00
abstract：:The integrated response to severe exercise involves fourfold to fivefold increases in cardiac output, which are due primarily to increases in cardiac rate and to a lesser extent to augmentation of stroke volume. The increase in stroke volume is partly due to an increase in end-diastolic cardiac size (Frank-Starling me...
journal_title：Progress in cardiovascular diseases
pub_type： 杂志文章,评审
doi：10.1016/0033-0620(76)90018-9
更新日期：1976-09-01 00:00:00
