Abstract:
:Endothelial dysfunction due to reduced bioavailability of nitric oxide (NO) is an early step in the course of atherosclerotic cardiovascular disease (CVD). NO is synthesized from L-arginine via the action of NO synthase (NOS), which is known to be blocked by endogenous L-arginine analogues such as asymmetric dimethylarginine (ADMA). ADMA is a naturally occurring amino acid found in plasma and various types of tissues. Recently, it has been demonstrated that plasma levels of ADMA are elevated in patients with diabetes. It has also been reported that elevated plasma levels of ADMA are associated with increased risks of nonfatal stroke and myocardial infarction in patients with early diabetic nephropathy. These findings suggest that the elevated ADMA in diabetes could contribute to acceleration of atherosclerosis in this population. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress. There is a growing body of evidence to show that AGEs are involved in the development and progression of atherosclerosis in patients with diabetes. Since ADMA is mainly metabolized by dimethylarginine dimethylaminohydrolase (DDAH), it is conceivable that the impairment of DDAH actions by AGEs could be one possible molecular mechanism of the ADMA elevation in diabetic patients. In this paper, we would like to propose the possible ways of testing our hypotheses. Does treatment with metformin, which has a potential effect on the inhibition of glycation reactions in vivo, decrease the levels of ADMA in diabetic patients? If the answer is yes, is this beneficial effect of metformin superior to that of other anti-diabetic agents with equihypoglycemic properties? Does treatment with pyridoxamine, a post-Amadori inhibitor (so-called Amadorins) of AGE formation, also reduce the levels of ADMA and subsequently improve endothelial dysfunction in diabetic patients? Are the ADMA-lowering effects of these agents associated with an increase of DDAH expression and/or activity in endothelial cells? These clinical studies could clarify whether AGEs are involved in the elevation of ADMA in patients with diabetes via suppression of DDAH expression and/or activity, thus providing a novel molecular mechanism for accelerated atherosclerosis in diabetes.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Yamagishi S,Ueda S,Okuda Sdoi
10.1016/j.mehy.2007.01.053subject
Has Abstractpub_date
2007-01-01 00:00:00pages
922-4issue
4eissn
0306-9877issn
1532-2777pii
S0306-9877(07)00120-Xjournal_volume
69pub_type
杂志文章abstract::Behcet's disease (BD) is a chronic, multisystem inflammatory disorder characterized by relapsing oral aphthous and genital ulcers, ocular inflammation, erythemanodosum and folliculitis-like lesions of the skin, arthritis, and central nervous system involvement. Its pathogenesis has not been fully elucidated but the et...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2009.01.046
更新日期:2009-07-01 00:00:00
abstract::Radiotherapy (RT) has been established to improve both local control as well as overall survival rates in breast cancer. However, RT especially in left-sided breast cancer also irradiates a portion of the heart. Radiation associated toxicity to the heart assumes significance because of improval in survival of breast c...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2011.12.009
更新日期:2012-03-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2012.10.007
更新日期:2013-01-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2007.10.012
更新日期:2008-01-01 00:00:00
abstract::The available epidemiological data for amyotrophic lateral sclerosis (ALS) support an infectious etiology and lead us to propose a new hypothesis. We examined older epidemiological data concerning categories of the population with increased incidence (aged people, people living in rural areas, farmers, breeders), more...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2006.04.070
更新日期:2006-01-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/s0306-9877(96)90453-3
更新日期:1996-08-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2004.04.029
更新日期:2004-01-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2020.109762
更新日期:2020-07-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2019.04.013
更新日期:2019-06-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2015.03.020
更新日期:2015-07-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2007.02.019
更新日期:2007-01-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2010.01.006
更新日期:2010-06-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2017.01.010
更新日期:2017-03-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2003.10.001
更新日期:2004-01-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2009.10.009
更新日期:2010-03-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2003.12.022
更新日期:2004-01-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(91)90261-v
更新日期:1991-10-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2017.02.003
更新日期:2017-04-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2006.05.027
更新日期:2006-01-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2014.03.008
更新日期:2014-06-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(79)90046-x
更新日期:1979-09-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2003.12.059
更新日期:2005-01-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2007.10.013
更新日期:2008-01-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2019.109370
更新日期:2019-11-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(85)90110-0
更新日期:1985-12-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 历史文章,杂志文章
doi:10.1016/s0306-9877(02)00348-1
更新日期:2003-01-01 00:00:00
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journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(93)90069-3
更新日期:1993-10-01 00:00:00
abstract::"Consciousness" "mood," "identity" and "personality" are all emergent properties from whole-brain organizations; these are typically disturbed in psychiatric disorders. This work proposes that the underlying etiopathology of mental disorders originates from disturbances to global brain dynamics, or "Globalopathies" th...
journal_title:Medical hypotheses
pub_type: 杂志文章,评审
doi:10.1016/j.mehy.2013.09.032
更新日期:2013-12-01 00:00:00
abstract::Gender differences in stem cell population have recently been identified. Blood and tissue samples from women showed consistent elevation of hematopoietic stem cell populations, mesenchymal stem cell populations and endothelial progenitor cells compared to men of similar ages. We and others have shown an increase in h...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2012.06.029
更新日期:2012-10-01 00:00:00
abstract::The disturbances of the 11p15.5 chromosomal region are associated with Beckwith-Wiedemann syndrome, Russell-Silver syndrome, Wilms tumor, IMAGe syndrome, and idiopathic hemihyperplasia. The aim of this research was to examine the hypothesis that 11p15.5 initially became unstable in the European population about 200 ye...
journal_title:Medical hypotheses
pub_type: 历史文章,杂志文章
doi:10.1016/j.mehy.2018.09.008
更新日期:2018-12-01 00:00:00