Abstract:
OBJECTIVE:Genome-wide association studies have linked variants of fat mass and obesity-associated protein (FTO) to obesity. However, the molecular function of FTO remains unclear. In this study, we sought to investigate the potential effects of FTO in modulating cholesterol deposition in macrophage foam cells, as well as whether FTO exerts antiatherosclerotic properties in apolipoprotein E-deficient mice. METHOD AND RESULTS:We transfected RAW264.7 cells with plasmids encoding a wild-type or mutant FTO gene (I367F). The upregulation of FTO markedly attenuated cholesterol ester accumulation in macrophages loaded with oxidized LDL, whereas the downregulation of FTO reversed this effect. Moreover, FTO attenuated the mRNA and protein expression of a scavenger receptor, CD36, which was accompanied by the decline of peroxisome proliferator-activated receptor γ protein. In addition, FTO enhanced the phosphorylation of AMP-activated protein kinase (AMPK)α and acetyl-CoA carboxylase, which was effectively suppressed by FTO small interfering RNA. Pretreatment with compound C or transfection with a dominant-negative AMPKα blocked the FTO-mediated upregulation of ATP-binding cassette transporter A1 and ATP-binding cassette transporter G1. Furthermore, FTO suppressed IL-1β secretion independent of the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 inflammasome. In-vivo experiments were performed using apolipoprotein E-deficient mice that were infected with adeno-associated virus serotype 9-derived vectors encoding a wild-type or mutant FTO gene. FTO overexpression prevented the formation of atherosclerotic plaques and markedly reduced the content of plasma total cholesterol and LDL cholesterol. Notably, the antiatherosclerotic properties of FTO were observed only in male mice. CONCLUSION:We propose that the FTO-dependent control of cholesterol deposition may provide avenues for the treatment of atherosclerosis.
journal_name
J Hypertensjournal_title
Journal of hypertensionauthors
Mo C,Yang M,Han X,Li J,Gao G,Tai H,Huang N,Xiao Hdoi
10.1097/HJH.0000000000001255subject
Has Abstractpub_date
2017-04-01 00:00:00pages
810-821issue
4eissn
0263-6352issn
1473-5598pii
00004872-201704000-00022journal_volume
35pub_type
杂志文章abstract:BACKGROUND:Small size at birth and greater BMI in childhood are associated with greater brachial blood pressure (BP) in later life. Aortic (central) BP differs from brachial BP and is more predictive of organ damage and cardiovascular events; the relationship between BMI in childhood and central BP is not known. METHO...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000269
更新日期:2014-09-01 00:00:00
abstract:OBJECTIVE:Studies were undertaken to clarify the pathophysiologic significance of endogenous endothelin in the control of blood pressure and renal hemodynamics in spontaneously hypertensive rats (SHR). DESIGN:The technique of passive immunization was used to neutralize endogenous endothelin in order to estimate the co...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract::The binding of 125I-angiotensin II to human blood cells was investigated. Blood was drawn from healthy volunteers and platelets prepared with minimal contamination of red cells and white blood cells (less than 0.1%). Using thin layer chromatography, degradation of 125I-angiotensin II by platelets could be demonstrated...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-198504000-00004
更新日期:1985-04-01 00:00:00
abstract:OBJECTIVES:Sodium is the mineral that has been, mainly, linked to hypertension and cardiovascular disease. It is found naturally in many foods, but is also used in the food industry and manufacturing. Identification of total sodium intake, as well as 'hidden' sodium intake from food sources early in life is necessary. ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e328345ef35
更新日期:2011-06-01 00:00:00
abstract:OBJECTIVE:This study evaluated the impact of prolonged circulatory unloading and subsequent left ventricular (LV) mass decrease on LV myocardial performance. Five-week head-down tilt (-6°) bed rest (HDTBR) was used as a model of prolonged circulatory unloading. METHODS:Ten young healthy male volunteers (age 23 ± 2 yea...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32833f5e01
更新日期:2011-01-01 00:00:00
abstract::The effects of age on the circadian blood pressure rhythm of patients with untreated essential hypertension (n = 133, World Health Organization stage I or II) were compared with those of normotensive subjects (n = 91). Subjects were classified into three groups by age: young (less than 40 years old), adult (40-59 year...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199105000-00004
更新日期:1991-05-01 00:00:00
abstract:OBJECTIVE:Hypertensive rats are more sensitive to the pressor effects of acute ouabain than normotensive rats. We analyzed the effect of chronic ouabain (approximately 8.0 microg/day, 5 weeks) treatment on the blood pressure of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats and the contribution of vascula...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32832a391f
更新日期:2009-06-01 00:00:00
abstract::Ischemic renal disease (IRD) is defined as a clinically important reduction in glomerular filtration rate or loss of renal parenchyma caused by hemodynamically significant renal artery stenosis. IRD is a common and often overlooked clinical entity that presents itself in the setting of extrarenal arteriosclerotic vasc...
journal_title:Journal of hypertension
pub_type: 社论,评审
doi:10.1097/00004872-199715120-00001
更新日期:1997-12-01 00:00:00
abstract:AIM:To investigate same day repeated measures and diurnal variation of arterial stiffness, cardiac output (CO), stroke volume (SV) and total peripheral resistance (TPR) during the third trimester of normal pregnancy. METHODOLOGY:Pulse wave velocity (PWV) and augmentation index (AIx) were recorded using the Arteriograp...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001482
更新日期:2017-12-01 00:00:00
abstract:OBJECTIVES:To investigate the effects of the interaction between adenosine receptors and renal nerves on urinary sodium excretion and glomerular filtration rate. METHODS AND DESIGN:The effects on water and sodium excretion and glomerular filtration rate of A1 [2-chloro-N6-cyclopentyl-adenosine (CCPA)] and A2 [2-hesiny...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199715120-00090
更新日期:1997-12-01 00:00:00
abstract:OBJECTIVE:It is not well known which exercise intensity is needed to obtain blood pressure reductions in response to endurance training. We therefore compared the effect of training at lower and higher intensity on blood pressure, and, in addition on other cardiovascular risk factors, in at least 55-year-old sedentary ...
journal_title:Journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1097/HJH.0b013e328322cf60
更新日期:2009-04-01 00:00:00
abstract:OBJECTIVE:Age, hypertension, diabetes mellitus and a history of cardiovascular disease are the most important factors related to the presence of cerebral white matter lesions (WML), which are a common finding in elderly people. This study investigates which factors related to hypertension per se are associated with the...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200203000-00028
更新日期:2002-03-01 00:00:00
abstract:OBJECTIVE:Pre-eclampsia is characterized by an increased vascular tone which might be related to an abnormal endothelial cell function. As representatives of the fetal circulation, we compared the nitric oxide (NO)-releasing capacity of human umbilical vessels from normal and pre-eclamptic pregnancies. METHODS:Normal ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract:BACKGROUND:Blood pressure (BP)-lowering trials studying efficacy mostly assesses binary outcome events, for example stroke/no stroke. Analysis of ordered categorical vascular events (e.g. three levels: fatal stroke/nonfatal stroke/no stroke) provides information on severity and is more powerful statistically than analy...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32833c7a32
更新日期:2010-10-01 00:00:00
abstract:BACKGROUND:The retinal microvasculature provides a window to the cerebral vasculature and enables examination of changes in retinal caliber that may mimic those occurring in cerebrovascular disease. The association of central arterial stiffness and retinal vessel caliber in a population sample is not fully understood. ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000002252
更新日期:2020-02-01 00:00:00
abstract:OBJECTIVE:The heptapeptide angiotensin-(1-7) [Ang-(1-7)] has been identified as a versatile, endogenous inhibitor of the renin-angiotensin system (RAS). As the therapeutic response to exogenous RAS inhibitors, such as AT1 receptor antagonists, is altered by changes in salt intake, we investigated the effect of a low, n...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200412000-00018
更新日期:2004-12-01 00:00:00
abstract:OBJECTIVE:Previous studies on multicellular preparations have shown that hypertrophied cardiac muscle from the spontaneously hypertensive rat (SHR) has a prolonged action potential. The first aim of the present study was to determine whether the action potential of isolated left ventricular myocytes was similarly prolo...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199306000-00005
更新日期:1993-06-01 00:00:00
abstract::Elevated large artery stiffness and pulse pressure have emerged as important risk factors for cardiovascular disease. The genders differ in large artery biomechanical properties throughout the lifespan with females displaying higher stiffness than males during the prepubertal years and a dramatic increase after menopa...
journal_title:Journal of hypertension
pub_type: 杂志文章,评审
doi:10.1097/HJH.0b013e328344da5e
更新日期:2011-06-01 00:00:00
abstract::Current opinions on the relationships between erythrocyte sodium-lithium countertransport kinetics and primary hypertension, hyperlipidaemia and diabetic nephropathy are reviewed. Problems associated with the assay are analysed. Some possible mechanisms that could modify the kinetics of ion exchange are examined. The ...
journal_title:Journal of hypertension
pub_type: 杂志文章,评审
doi:10.1097/00004872-199816010-00002
更新日期:1998-01-01 00:00:00
abstract:OBJECTIVE:To assess the trends in blood pressure (BP) and in body mass index (BMI) in the hypertensive and normotensive population in Finland during 1982-1997. DESIGN:Four independent cross-sectional standardized population surveys were conducted in 1982, 1987, 1992 and 1997. SETTING:The provinces of North Karelia an...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200018030-00003
更新日期:2000-03-01 00:00:00
abstract:OBJECTIVE:An excess morning blood pressure surge (MBPS) may portend an increased cardiovascular risk, but the mechanisms thereof have been little investigated. The link between MBPS, short-term blood pressure (BP) variability, and arterial stiffness has not been entirely defined. METHODS:In 602 consecutive untreated h...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001153
更新日期:2017-02-01 00:00:00
abstract:BACKGROUND:Fibromuscular dysplasia (FMD) and atherosclerotic renal artery stenosis (ARAS) are the most common causes of renovascular hypertension. So far, FMD is believed to cause hypertension via similar mechanisms as in ARAS, that is, a decrease in renal blood flow, which subsequently leads to increased renin secreti...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001243
更新日期:2017-04-01 00:00:00
abstract::Graft-prosthesis and stentgraft placements are effective modalities for treating abdominal aortic aneurysm, but related changes in arterial stiffness are not well established. The present study sought to assess aortic stiffness after aneurism repair by measuring pulse wave velocity (PWV). The graft-related variation o...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e3283299b22
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND:In the BEtter control of BP in hypertensive pAtients monitored Using the HOTMAN sYstem study, we investigated whether utilizing noninvasive monitoring of hemodynamic parameters combined with a drug selection algorithm (integrated hemodynamic management - IHM) compared with conventional drug selection may imp...
journal_title:Journal of hypertension
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/HJH.0000000000000749
更新日期:2015-12-01 00:00:00
abstract:OBJECTIVE:The aim of the present study was to examine the reproducibility of arterial baroreflex sensitivity (BRS) provided by the spontaneous baroreflex method at rest and during laboratory tests. METHODS:Twenty healthy volunteers were studied 24 h apart, in the same laboratory and under the same environmental condit...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199609000-00009
更新日期:1996-09-01 00:00:00
abstract:OBJECTIVE:Arterial remodeling aims to maintain a constant circumferential wall stress (sigmac). A failing remodeling process is associated with stroke. Data on the relationship between chronic kidney disease and arterial remodeling are scarce. METHODS:We investigated the association between a lower glomerular filtrati...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e3282f50066
更新日期:2008-04-01 00:00:00
abstract:OBJECTIVES:The genes responsible for obesity are also candidate genes for obesity-related conditions, such as hypertension and type 2 diabetes. A functional polymorphism in the uncoupling protein 2 (UCP2) promoter has been reported to be associated with obesity in Caucasians. To clarify the contribution of this polymor...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200401000-00018
更新日期:2004-01-01 00:00:00
abstract:AIM:Advanced age is associated with vascular endothelial dysfunction, characterized by reductions in the endothelium-dependent vasodilation of the conduit and resistance arteries, in part, from decreased nitric oxide bioavailability. Although vascular smooth muscle function (SMF), assessed by responsiveness to an exoge...
journal_title:Journal of hypertension
pub_type: 杂志文章,meta分析,评审
doi:10.1097/HJH.0000000000000446
更新日期:2015-03-01 00:00:00
abstract::Arterial aging is associated with a progressive increase in aortic stiffening, which results in a rise in central aortic pressures. Traditionally, blood pressure (BP)-lowering therapy has been directed at brachial rather than central pressures. However, a key contemporary question is whether this strategy is optimal i...
journal_title:Journal of hypertension
pub_type: 杂志文章,评审
doi:10.1097/HJH.0b013e328353e523
更新日期:2012-06-01 00:00:00
abstract::Precapillary resistance arteries from spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) were found to contain three inositol lipids and to produce five inositol phosphate peaks. These were assessed by a highly sensitive procedure which involved the separation of radiolabelled inositol-cont...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199006000-00009
更新日期:1990-06-01 00:00:00