Abstract：
:Atherosclerosis and its fatal complications, such as myocardial infarction or stroke, represent the most common cause of morbidity or mortality in modern world. It was observed that an excess of reactive oxygen species (ROS) accompanies atherosclerosis. Under physiological circumstances, intracellular H+ accumulates and cell membrane depolarizes during ROS production, rendering ROS generation self-limiting and thus avoiding oxidative stress. However, the persistent production of ROS during atherosclerosis suggests that the physiologically self-limiting ROS-generating process was somehow disrupted and there may be an as-yet unknown mechanism supporting unlimited ROS generation. We thus postulated that an outward H+ conductance, which can efficiently export H+ from the cytosol and maintain membrane potential, may play a crucial role during atherosclerosis. So far, Hv1 channels were mainly found in immune cells (macrophages, neutrophils). As large quantities of vascular infiltrating macrophages exist, we proposed that Hv1-mediated oxidative stress promoted excessive ROS production and the formation of foam cells, contributing to atherosclerosis. In addition, we could not exclude the possibility that Hv1 channels may be upregulated in vascular cells under atherosclerotic conditions, which may also exert effects on vascular inflammation and fibrous cap formation. The present study will employ Hv1 knockout mice in combination with in vitro studies to explore the role of Hv1 channel in atherosclerosis and dissect the underlying mechanisms. The results are expected to offer novel insights into the pathogenesis of atherosclerosis as well as clues for developing novel therapeutic avenues.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Zheng Z,Zhang Z,Wang Mdoi
10.1016/j.mehy.2020.109724subject
Has Abstractpub_date
2020-08-01 00:00:00pages
109724eissn
0306-9877issn
1532-2777pii
S0306-9877(20)30361-3journal_volume
141pub_type
杂志文章abstract：:On March 11, 2020, the World Health Organization declared the coronavirus outbreak a pandemic. Since December 2019, the world has experienced an outbreak of coronavirus disease 2019 (COVID-19). Epidemiology, risk factors, and clinical characteristics of patients with COVID-19 have been reported but the factors affecti...
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
abstract：:The objective of this work is to propose a biomechanical model of sacro-iliac joint dysfunction as a cause of low back pain. Sacro-iliac joint is known to be a source of low back pain. We also know that it is a very stable joint with little mobility. Surrounding lower limb and back muscles contribute a major part of t...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2005.02.035
更新日期：2005-01-01 00:00:00
abstract：:In endemic pemphigus foliaceus (EPF) or "fogo selvagem" the epidemiological evidence shows that all the described outbreaks occur on the banks of rivers where there is mercury contamination from alluvium gold mining and deforestation. Pathophysiological evidence shows a similarity to pemphigus induced by sulphydryl (S...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2011.09.041
更新日期：2012-01-01 00:00:00
abstract：:Following the rate of proteoglycan synthesis as the metabolic parameter of the growth of cartilage cells, indicates that hormonal and local agents are two distinct types of extracellular regulators responsible for altering the basic metabolic rates of cells. Such changes in growth rate occur regularly at physiological...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(80)90057-2
更新日期：1980-04-01 00:00:00
abstract：:According to the theory presented herewith, neoplasia results solely from stem cell depletion. Besides serving as tissue progenitors, stem cells are postulated to secrete a vital substance 'A' necessary for proper tissue function. Carcinogens interfere with 'A' production mainly by destroying stem cells and since the ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(85)90026-x
更新日期：1985-11-01 00:00:00
abstract：:In UK educational circles it has long been regarded as a platitude that a good scientific education at school and undergraduate level should aim to teach critical thinking and encourage students to challenge mainstream science, debate scientific issues and express their personal opinions. However, I believe that this ...
journal_title：Medical hypotheses
pub_type： 社论
doi：10.1016/j.mehy.2009.07.050
更新日期：2010-02-01 00:00:00
abstract：:The Davson-Danielli model of the cell membrane accounted for nearly all the space within it by suggesting that it was composed of structural proteins and lipids; this would leave virtually no space for the large number of enzymes, carriers, antigens, antibodies, and receptors for hormones, transmitters, drugs and toxi...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(88)90100-4
更新日期：1988-07-01 00:00:00
abstract：:Curvilinear distraction is currently under investigation to reconstruct curved maxillofacial bone defects. However, previous studies have revealed the discrepancy between the contour of the regenerated bone in the distraction gap and the curvilinear pathway of the transport disc. We hypothesize that the discrepancy is...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.06.011
更新日期：2012-10-01 00:00:00
abstract：:Recently, the metabolic routes for acetone metabolism have been described. Therefore, acetone cannot further be regarded as a waste product of metabolism. However, its physiological role in biochemical machinery is not clear. Here, an integrative model for the role of acetone metabolism is presented that orders the ev...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.1998.0752
更新日期：1999-09-01 00:00:00
abstract：:Condylar cartilage is absolutely necessary for the normal function of temporomandibular joint (TMJ). Unfortunately, condylar cartilage defect or missing is also one of the common clinical problems. Repair or reconstruction of cartilage is always a hot topic. Cell based cartilage regeneration is suggested as novel ther...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2011.03.045
更新日期：2011-07-01 00:00:00
abstract：:Dietary chromium supplementation for the treatment of diabetes remains controversial. The prevailing view that chromium supplementation for glucose regulation is unjustified has been based upon prior studies showing mixed, modest-sized effects in patients with type 2 diabetes (T2DM). Based on chromium's potential to i...
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
abstract：:It has been hypothesized that sulfite oxidase deficient persons may be at increased risk to toxicity from SO2 and dietary sulfites widely used for food preservation. Sulfite oxidase is believed to be responsible for the detoxification of SO2 and/or sulfite to sulfate for excretion. Human and animal studies have shown ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(81)90110-9
更新日期：1981-02-01 00:00:00
abstract：:The hypterphosphorylation of tau proteins is a well-established step in the expression of the pathological features in Alzheimer's disease (AD). While a primary event that links aluminum and AD, the so-called 'aluminum hypotheses', is far from being demonstrated, however, the metal ion could be an important etiologica...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(95)90131-0
更新日期：1995-03-01 00:00:00
abstract：:ATP sensitive (K(+)(ATP)) potassium cardiac channels are recruited when ATP levels are low as in ischemic injury and acute trauma. Such activation results in ECG-ST elevation and cardiac arrhythmias. K(+)(ATP) channel recruitment may be blocked by the sulfonylurea glibenclamide, permitting a wide variety of animal exp...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(03)00055-0
更新日期：2003-04-01 00:00:00
abstract：:Posterior capsule opacification (PCO) is a debilitating and relatively common complication of cataract surgery despite modern medical and surgical advances. The pathophysiology of this condition has largely been attributed to peptide mediators, such as transforming growth factor-beta (TGFβ), epidermal growth factor (E...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.12.042
更新日期：2013-04-01 00:00:00
abstract：:Recent investigations on protease inhibitors in articular cartilage have provided new insights into the possible initial lesions of osteoarthrosis. A hypothesis has been formulated based upon an impaired ability of chondrocytes to synthesize protease inhibitors, which leads to loss of matrix integrity and vascular inv...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(79)90041-0
更新日期：1979-07-01 00:00:00
abstract：:The molecular similarity between certain human antigenic determinants with those of HIV has been already described. In this matter, we have previously demonstrated, by a chromatographic method, the cross reactivity of human serum albumin with HIV gp 120. The hypothesis that this similarity could be one of the reasons ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.2001.1520
更新日期：2002-05-01 00:00:00
abstract：:Oxidative stress-mediated neurodegeneration is responsible for 12% mortality around the globe. Alzheimer's Disease (AD) and Parkinson's Disease (PD) are the most prevalent neurodegenerative diseases, associated with modulation of acetylcholine levels and amyloid beta accumulation & dopamine level and alpha-synuclein o...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2020.109872
更新日期：2020-10-01 00:00:00
abstract：:Although once considered by biologists almost exclusively for their toxicity, reactive oxygen (ROS) and nitrogen (RNS) species produced within normal cells under baseline physiological conditions are now appreciated as redox regulators of a wide range of protein functions. Two families of enzymes, the NADPH oxidases (...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2019.109249
更新日期：2019-08-01 00:00:00
abstract：:Abdominal aortic aneurysms (AAAs) have traditionally been attributed to atherosclerosis, although there is increasing epidemiological, biochemical and genetic evidence that aneurysmal arterial disease is different from occlusive atherosclerosis. One of the most consistent biochemical findings in the aneurysmal aorta i...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(95)90193-0
更新日期：1995-07-01 00:00:00
abstract：:The role of ozone on earth is controversial, as in the stratosphere it is protective against excessive ultra violet irradiation, and in the troposphere it is toxic for animals and plants. The effectiveness of ozone against pathogens is well recognized and ozone appears to be the best agent for sterilization of water. ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(96)90016-x
更新日期：1996-02-01 00:00:00
abstract：:High fat and low carbohydrate diet, designated ketogenic diet, has been successfully used for the treatment of intractable epilepsy in a portion of patients, particularly in children. Several hypotheses have been worked out for the explanation of its beneficial effects, among others acetone has been raised as a causat...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2006.10.041
更新日期：2007-01-01 00:00:00
abstract：:Mental retardation is a progressive condition in Down syndrome: intelligence starts to decline linearly within the first year. This phenomenon could be related to the overproduction of a toxic compound, hydrogen sulfide. Indeed, a gene located on chromosome 21 controls the production of cystathionine-β-synthase, an en...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2019.109289
更新日期：2019-10-01 00:00:00
abstract：:Inflammation integrates diverse mechanisms that are associated not only with pathological conditions, such as cardiovascular diseases, type 2 diabetes, obesity, neurodegenerative diseases and cancer, but also with physiological processes like reproduction i.e. oogenesis and embryogenesis as well as aging. In the curre...
journal_title：Medical hypotheses
pub_type： 杂志文章,评审
doi：10.1016/j.mehy.2012.02.018
更新日期：2012-06-01 00:00:00
abstract：:In this communication I propose a technique for manipulating the idiotype anti-idiotype network with the aim of enhancing the immune response to tumors. The theoretical basis for this technique follows from Jerne's network theory of the immune system. By tolerizing the host to immunoglobulin bearing idiotypes directed...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(85)90029-5
更新日期：1985-11-01 00:00:00
abstract：:Numerous studies have shown that opioids and cannabinoids share some pharmacological properties. Accordingly, similarly to opioids, tolerance and dependence develops after chronic use of cannabinoids. Nitric oxide (NO) has been shown to play important roles both in opioid- and cannabinoid-induced tolerance and depende...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2009.02.013
更新日期：2009-08-01 00:00:00
abstract：:Obesity is a major public health problem, which occurs in epidemic proportions. Our understanding of the systems of the brain related to energy balance has increased over the last decade. As a result, drugs most commonly used today in the management of obesity have their primary effect in modulating the balance betwee...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2003.12.030
更新日期：2004-01-01 00:00:00
abstract：:Postoperative delirium represents a serious complication after major surgery. Patients suffer from anxiety, hallucinations and delusions, and have higher postoperative morbidity and mortality. Generally, the role of acetylcholine deficiency in delirium pathophysiology is widely accepted. How this pathologic state evol...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2006.07.003
更新日期：2007-01-01 00:00:00
abstract：:We developed a new hypothesis claiming that natriuresis of fasting is not only caused by diminished insulin resistance and hyperinsulinaemia with the subsequent reduction of renal sodium retention but it can also be attributed to the function of the leptin-NPY system. Each element of this concept has been substantiate...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.2000.1176
更新日期：2001-05-01 00:00:00
abstract：:Apoptosis is defined as the process of ''programmed cell death'' (PCD), during which many cells simultaneously die from within along a very orderly pattern. PCD is as intrinsic for cells as mitosis and is involved in both degenerative and developmental processes of organs and organisms. The pattern of apoptotic cell d...
journal_title：Medical hypotheses
pub_type： 社论
doi：10.1016/j.mehy.2007.07.006
更新日期：2008-01-01 00:00:00
