Abstract:
OBJECTIVE:Similar to cancer, pulmonary arterial hypertension (PAH) is characterized by vascular remodeling, which leads to obliteration of the small pulmonary arteriole, with marked proliferation of pulmonary artery smooth muscle cells (PASMC) and/or endothelial cells dysfunction. Aberrant expression of tumor suppressor genes is closely associated with susceptibility to PAH. We hypothesized that α-solanine, a glycoalkaloid found in members of the nightshade family known to have antitumor activity in different cancers, reverses experimental PAH by activating the tumor suppressor-axis inhibition protein 2 (AXIN2). METHODS AND RESULTS:We investigated the effects of α-solanine on PASMC proliferation and apoptosis by using 5-ethynyl-2'-deoxyuridine proliferation assay, proliferating cell nuclear antigen and Ki67 staining, TUNEL and Anexine V assays. Scratch wound healing and tube formation assays were also used to study migration of endothelial cells. In vitro, we demonstrated, using cultured human PASMC from PAH patients, that α-solanine reversed dysfunctional AXIN2, β-catenin and bone morphogenetic protein receptor type-2 signaling, whereas restored [Ca]i, IL-6 and IL-8, contributing to the decrease of PAH-PASMC proliferation and resistance to apoptosis. Meanwhile, α-solanine inhibits proliferation, migration and tube formation of PAH-pulmonary artery endothelial cells by inhibiting Akt/GSK-3α activation. In vivo, α-solanine administration decreases distal pulmonary arteries remodeling, mean pulmonary arteries pressure and right ventricular hypertrophy in both monocrotaline-induced and Sugen/hypoxia-induced PAH in mice. CONCLUSION:This study demonstrates that AXIN2/β-catenin axis and Akt pathway can be therapeutically targeted by α-solanine in PAH. α-Solanine could be used as a new therapeutic strategy for the treatment of PAH.
journal_name
J Hypertensjournal_title
Journal of hypertensionauthors
Nie X,Dai Y,Tan J,Chen Y,Qin G,Mao W,Zou J,Chang Y,Wang Q,Chen Jdoi
10.1097/HJH.0000000000001475subject
Has Abstractpub_date
2017-12-01 00:00:00pages
2419-2435issue
12eissn
0263-6352issn
1473-5598journal_volume
35pub_type
杂志文章abstract:OBJECTIVE:It has been shown that angiotensin-converting enzyme inhibition or angiotensin receptor blockade may improve endothelial dysfunction, an early manifestation of atherosclerosis, in patients with diabetes. Whether this protective effect is mediated through blood pressure-lowering effects or other specific mecha...
journal_title:Journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1097/HJH.0b013e3280287a72
更新日期:2007-04-01 00:00:00
abstract:BACKGROUND:Renal infarction can cause abrupt and severe hypertension and less frequently renal failure. Renal infarction results from disruption of renal blood flow in the main ipsilateral renal artery or in a segmental branch. Underlying mechanism is either general, 'embolic' or 'thrombophilic', or local related to pr...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001588
更新日期:2018-03-01 00:00:00
abstract:BACKGROUND:Although the benefit of hypertension treatment is well established in high-risk patients, there is a paucity of evidence regarding the benefit of treatment in patients with uncomplicated hypertension. METHODS:Hypertensive adult patients were selected from the Korea National Health Insurance Sample Cohort in...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001331
更新日期:2017-05-01 00:00:00
abstract::Fish and fish oils have been reported to reduce blood pressure in normotensives and untreated hypertensives. The present study examined the effect of dietary supplementation with fish oil on blood pressure in 20 treated hypertensives with controlled blood pressures who continued their usual antihypertensive drug treat...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004872-199004000-00007
更新日期:1990-04-01 00:00:00
abstract:OBJECTIVE:To investigate whether nondipping and diabetes are independently related to metabolic risk profile and prevalence of target organ damage in a population setting. METHODS:A population-based cohort of 70-year-old men (n = 1057) was examined with 24-h ambulatory blood pressure monitoring, euglycemic hyperinsuli...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200208000-00011
更新日期:2002-08-01 00:00:00
abstract:OBJECTIVE:To examine the relationship between blood pressure and depression in a large sample of noninstitutionalized elderly people. METHODS:Cross-sectional community-based study in 9294 participants aged 65 years and over, living at home, in three French cities (Bordeaux, Dijon and Montpellier). Participants were ca...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e3283088d1f
更新日期:2008-09-01 00:00:00
abstract::To evaluate factors influencing hemodynamic responses to psychological and physical stress, 117 normotensive college students were studied. The standardized tests included arithmetic, Stroop word-color, mirror draw, isometric handgrip and cold pressor challenges. The responses of blood pressure and pulse during the te...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1097/00004872-199010000-00012
更新日期:1990-10-01 00:00:00
abstract::Twenty-four adolescent boys with a positive and 40 boys with a negative parental history of hypertension (PH+ and PH-, respectively) were studied at rest and during exercise on a bicycle ergometer at work loads ranging from 25 to 150 W. Each group was divided into fit and unfit categories on the basis of oxygen consum...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract:OBJECTIVE:To determine adrenocorticotrophin dose-response relationships for increase of blood pressure and metabolic parameters of the Sprague-Dawley rat. METHODS:We injected 120 male Sprague-Dawley rats twice daily subcutaneously for 10 days with 0.5, 1, 5, 50, 100, 200 or 500 microg/kg synthetic adrenocorticotrophin...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199816050-00006
更新日期:1998-05-01 00:00:00
abstract:OBJECTIVE:We attempted to determine a valid pharmacological approach for the control of high blood pressure in obese hypertensive patients using two antihypertensive agents with different pharmacological actions. DESIGN:Thirty-two obese hypertensive black women were randomly treated with chlorthalidone or clonidine to...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004872-199205000-00013
更新日期:1992-05-01 00:00:00
abstract::The postulated antihypertensive effect of dietary fish oil and the influence of dietary sodium on this effect were evaluated in young stroke-prone spontaneously hypertensive rats (SHRSP) by direct intra-arterial measurement of blood pressure. Weaning rats were fed synthetic diets containing olive oil or eicosapentaeno...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199107000-00009
更新日期:1991-07-01 00:00:00
abstract:OBJECTIVE:To evaluate whether efficacious counseling methods on sodium restriction can be successfully incorporated into primary care models for the management of hypertension. METHODS:We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Te...
journal_title:Journal of hypertension
pub_type: 杂志文章,评审
doi:10.1097/HJH.0000000000000182
更新日期:2014-07-01 00:00:00
abstract:OBJECTIVES:The interaction between trophoblasts and maternal endothelium is important for placental vascular modeling. Failure of uterine spiral artery transformation is linked to the etiopathology of preeclampsia. Antihypertensive medications used to control hypertension in early pregnancy can alter placental and circ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000134
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:The effects of aspirin in subjects without cardiovascular disease are controversial. In the intensively treated patients of the Hypertension Optimal Treatment (HOT) Study, randomization to low-dose aspirin (75 mg daily) versus placebo significantly reduced cardiovascular events (-15%) and myocardial infarcti...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004872-200211000-00031
更新日期:2002-11-01 00:00:00
abstract:OBJECTIVE:Patients with essential hypertension exhibit several red blood cell (RBC) ion transport abnormalities, insulin resistance (IR) and increased risk of developing type 2 diabetes. The aims of this study were to assess RBC ion transport activities under basal conditions and to test the in vivo effect of acute hyp...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200307000-00021
更新日期:2003-07-01 00:00:00
abstract:OBJECTIVES:The long-term consequences of extreme prematurity are becoming increasingly important, given recent improvements in neonatal intensive care. The aim of the current study was to examine the cardiovascular consequences of extreme prematurity in 11-year-olds born at or before 25 completed weeks of gestation. M...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e328347e333
更新日期:2011-07-01 00:00:00
abstract:OBJECTIVES:Many different stress echocardiographic and radionuclide perfusion imaging tests have been proposed for detecting epicardial coronary artery disease (CAD) in hypertensive patients. Their relative diagnostic and prognostic value has not been exactly established. BACKGROUND:A positive exercise electrocardiogr...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200103000-00018
更新日期:2001-03-01 00:00:00
abstract::Recent evidence suggests that a considerable proportion of plasma angiotensin is generated not in blood but in peripheral tissues. Through the measurement of angiotensin peptides and renin in the plasma of 11 anephric subjects, we have investigated whether kidney-derived renin, or some other tissue mechanism for angio...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199103000-00011
更新日期:1991-03-01 00:00:00
abstract:BACKGROUND:The objective of this study was to estimate the prevalence and distribution of hypertension and to determine the status of hypertension awareness, treatment and control in the Portuguese adult population. METHODS:This study was conducted in 2003, and a multistage cluster sampling method was used to select a...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000179908.51187.de
更新日期:2005-09-01 00:00:00
abstract:BACKGROUND:We demonstrated in a previous cross-sectional study that arterial compliance is elevated in postmenopausal women taking estrogen-containing hormonal therapy, which may partially account for the reduction in cardiovascular risk observed. OBJECTIVE:To investigate the effects of withdrawal and recommencement o...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199917030-00015
更新日期:1999-03-01 00:00:00
abstract:OBJECTIVE:Coronary heart disease (CHD) risk factors have been consistently related to an increase in carotid intima-media thickness (IMT) in selected populations. However, few studies were population-based and furthermore little attention has been given to the influence of CHD risk factors on IMT in low-risk population...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199917060-00004
更新日期:1999-06-01 00:00:00
abstract::Isolated tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP), but not from normotensive Wistar-Kyoto rats (WKY), exhibit oscillatory contractions in response to norepinephrine. Previous studies indicate that the mechanism for these oscillations involves altered membrane calcium and/or potassium han...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-198901000-00005
更新日期:1989-01-01 00:00:00
abstract:OBJECTIVE:The optimal time to initiate antihypertensive therapy among patients with acute ischemic stroke remains uncertain. We tested the effects of blood pressure reduction among patients with acute ischemic stroke according to time from onset to initiation of antihypertensive treatment. METHODS:We randomly assigned...
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.0000000000001288
更新日期:2017-06-01 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:Development of internally quenched fluorogenic substrates for sensitive and continuous assays of angiotensin I-converting enzyme (ACE). DESIGN:We synthesized internally quenched fluorogenic bradykinin-related peptides introducing Abz (ortho-aminobenzoic acid) and EDDnp (N-[2,4-dinitrophenyl]-ethylenediamine)...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199917050-00010
更新日期:1999-05-01 00:00:00
abstract::Ca2+ pump kinetics were investigated in erythrocytes from 22 essential hypertensive patients and 20 normotensive controls (under initial-rate and steady-state conditions, using Sr2+ as a Ca2+ analogue). The mean value of the apparent dissociation constant for total internal Ca2+ (KCa) was slightly but significantly in...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract:OBJECTIVE:Spontaneously hypertensive rats (SHR) are sensitive to a high salt intake and we investigated the question of whether flow-induced dilation is affected by this type of diet, as flow responses are especially sensitive to small changes in extracellular sodium concentrations. METHODS:We evaluated the effects of...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199816100-00013
更新日期:1998-10-01 00:00:00
abstract:OBJECTIVE:We examined the effects of treatment with soluble epoxide hydrolase inhibitor (sEHi) and epoxyeicosatrienoic acids (EETs) analogue (EET-A), given alone or combined, on blood pressure (BP) and ischemia/reperfusion myocardial injury in rats with angiotensin II (ANG II)-dependent hypertension. METHODS:Ren-2 tra...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001708
更新日期:2018-06-01 00:00:00
abstract::Endothelin-1 was infused into the non-dominant brachial artery in two male subjects. We then monitored intra-arterial mean blood pressure, right atrial pressure, the heart rate and forearm blood flow (by plethysmography). Endothelin-1 at a dose of 5 x 10(-14) to 5 x 10(-9) mol, infused over 5 min periods, elicited no ...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1097/00004872-199009000-00004
更新日期:1990-09-01 00:00:00
abstract:OBJECTIVE:Caffeine is the most widely used pharmacologically active substance. Aortic elastic properties and arterial wave reflection are important factors for the efficient performance of the cardiovascular system, as well as prognosticators of cardiovascular risk. We investigated the effect of caffeine on aortic elas...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004872-200303000-00022
更新日期:2003-03-01 00:00:00