Apelin protects against angiotensin II-induced cardiovascular fibrosis and decreases plasminogen activator inhibitor type-1 production.


OBJECTIVE:To test the hypothesis that apelin protects against angiotensin II (Ang II)-induced cardiovascular fibrosis and vascular remodeling. METHODS AND RESULTS:Wild-type mice administered apelin or apelin along with Ang II exhibited less cardiovascular fibrosis and decreased plasminogen activator inhibitor type-1 (PAI-1) gene expression than mice receiving Ang II, N-nitro-L-arginine methyl ester (L-NAME), apelin plus L-NAME or apelin plus Ang II plus L-NAME. In-vitro analysis using a luciferase construct driven by 3.1 kb of the human PAI-1 promoter revealed that apelin blocked Ang II-mediated PAI-1 gene expression. Immunoblotting for phosphorylated myosin phosphatase subunit and myosin light chain revealed that apelin blocked Ang II activation of the Rho kinase pathway, which is associated with induction of PAI-1 gene expression by Ang II. In addition, treatment of human aortic smooth muscle cells with apelin reduced PAI-1 mRNA and protein production in the presence and absence of Ang II. Conversely, L-NAME treatment attenuated the downregulation of PAI-1 by apelin in cells. CONCLUSION:Apelin protects against cardiac fibrosis and vascular remodeling through direct regulation of PAI-1 gene expression. This protective effect is mediated through the synergistic inhibition of Ang II signaling and increased production of nitric oxide by apelin. Our data extend previous findings and provide new insight into the molecular mechanisms by which apelin elicits a cardioprotective effect.


J Hypertens


Journal of hypertension


Siddiquee K,Hampton J,Khan S,Zadory D,Gleaves L,Vaughan DE,Smith LH




Has Abstract


2011-04-01 00:00:00












  • Prestroke treatment with beta-blockers for hypertension is not associated with severity and poor outcome in patients with ischemic stroke: data from a national stroke registry.

    abstract:BACKGROUND:Beta-blockers are not recommended as the initial therapy for hypertension. Reports on associations between use of beta-blockers and stroke severity are inconclusive. We assessed associations between prestroke use of beta-blockers and stroke severity, poststroke disability and death in a large group of hypert...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Koton S,Tanne D,Grossman E

    更新日期:2017-04-01 00:00:00

  • Cardiovascular autonomic profile in women with constitutional hypotension.

    abstract:BACKGROUND:Constitutional hypotension (CHT) is defined as a SBP below 105 mmHg. As autonomic-related symptoms are frequently reported in CHT, these symptoms suggest that the cardiovascular autonomic control is perturbed in individuals with CHT. METHODS:We investigated the autonomic cardiovascular control of 15 women w...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Jacob G,Barbic F,Glago M,Dipaola F,Porta A,Furlan R

    更新日期:2018-10-01 00:00:00

  • Validation and comparison of three formulae to estimate sodium and potassium excretion from a single morning fasting urine compared to 24-h measures in 11 countries.

    abstract:BACKGROUND AND OBJECTIVES:Although 24-h urinary measure to estimate sodium and potassium excretion is the gold standard, it is not practical for large studies. We compared estimates of 24-h sodium and potassium excretion from a single morning fasting urine (MFU) using three different formulae in healthy individuals. M...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Mente A,O'Donnell MJ,Dagenais G,Wielgosz A,Lear SA,McQueen MJ,Jiang Y,Xingyu W,Jian B,Calik KB,Akalin AA,Mony P,Devanath A,Yusufali AH,Lopez-Jaramillo P,Avezum A Jr,Yusoff K,Rosengren A,Kruger L,Orlandini A,Rangar

    更新日期:2014-05-01 00:00:00

  • Adjustment for current weight and the relationship between birth weight and blood pressure in childhood.

    abstract:OBJECTIVE:To determine the role of current weight in mediating the relationship between birth weight and blood pressure within the context of the 'fetal origins' hypothesis. DESIGN:Prospective cohort study of 2507 pregnant women and their singleton offspring, delivered live at term, in Perth, Western Australia between...

    journal_title:Journal of hypertension

    pub_type: 临床试验,杂志文章


    authors: Blake KV,Gurrin LC,Evans SF,Beilin LJ,Stanley FJ,Landau LI,Newnham JP

    更新日期:2000-08-01 00:00:00

  • The predictive role of CHA2DS2-VASc score between venous thromboembolism and ischemic stroke: a large-scale cohort study.

    abstract:PURPOSE:This study aimed to explore the predictive role of CHA2DS2-VASc score between venous thromboembolism (VTE) and ischemic stroke. METHODS:The current study was analyzed from the in-patient claims data of the Taiwan National Health Insurance Research Database. We identified the patients diagnosed with VTE (for St...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Hu WS,Lin CL

    更新日期:2018-03-01 00:00:00

  • Cardioprotective effect of angiotensin II type 1 receptor antagonist associated with bradykinin-endothelial nitric oxide synthase and oxidative stress in Dahl salt-sensitive hypertensive rats.

    abstract:OBJECTIVES:The interactions between eNOS or oxidative stress and bradykinin under long-term treatment of angiotensin II type 1 receptor antagonists (ATRA) remain unknown. To elucidate the molecular mechanisms of the cardioprotective effect of ATRA, we evaluated whether valsartan affects the bradykinin-eNOS and nicotina...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Yoshida K,Kobayashi N,Ohno T,Fukushima H,Matsuoka H

    更新日期:2007-08-01 00:00:00

  • Time-of-day of energy intake: association with hypertension and blood pressure 10 years later in the 1946 British Birth Cohort.

    abstract:OBJECTIVES:The role of circadian rhythm of energy and macronutrient intake in influencing cardiometabolic risk factors is increasingly recognized. However, little is known of the association between time of energy intake and blood pressure. We examined the association between time-of-day of energy intake and subsequent...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Almoosawi S,Prynne CJ,Hardy R,Stephen AM

    更新日期:2013-05-01 00:00:00

  • Use of the oral contraceptive pill is associated with increased large artery stiffness in young women: the ENIGMA study.

    abstract:BACKGROUND:The oral contraceptive pill (OCP) is widely prescribed throughout the world. Although it is associated with a small but significant increase in blood pressure, the influence of the OCP on large artery stiffness and wave reflection is unclear. The aim of this study was to determine the relationship between us...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Hickson SS,Miles KL,McDonnell BJ,Yasmin,Cockcroft JR,Wilkinson IB,McEniery CM,ENIGMA Study Investigators.

    更新日期:2011-06-01 00:00:00

  • The obese gene product, leptin: possible role in obesity-related hypertension in adolescents.

    abstract:OBJECTIVE:The mechanism of the association between obesity and hypertension is not clear. The recently discovered obese gene product, leptin, the levels of which increase in obese subjects, has been shown to reduce food intake and increase sympathetic nervous system activity in animal studies. The present study was und...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Hirose H,Saito I,Tsujioka M,Mori M,Kawabe H,Saruta T

    更新日期:1998-12-01 00:00:00

  • Subtype diagnosis, treatment, complications and outcomes of primary aldosteronism and future direction of research: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension.

    abstract::: Primary aldosteronism is a frequent cause of secondary hypertension requiring a specific pharmacological treatment with mineralocorticoid receptor antagonist or with unilateral adrenalectomy. These treatments have shown to reduce the excess of cardiovascular risk characteristically associated with this disease. In p...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Mulatero P,Sechi LA,Williams TA,Lenders JWM,Reincke M,Satoh F,Januszewicz A,Naruse M,Doumas M,Veglio F,Wu VC,Widimsky J

    更新日期:2020-06-25 00:00:00

  • Prospective comparison of therapeutical attitudes in hypertensive type 2 diabetic patients uncontrolled on monotherapy. A randomized trial: the EDICTA study.

    abstract:OBJECTIVE:To compare the anti-hypertensive effect of combination therapy versus a single drug regimen schedule (dose-titration or switching to a different drug class) in type 2 diabetic hypertensive patients with inadequate blood pressure (BP) control on monotherapy. DESIGN:Prospective, randomized, open-fashion, paral...

    journal_title:Journal of hypertension

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Ruilope LM,de la Sierra A,Moreno E,Fernández R,Garrido J,de la Figuera M,de la Cámara AG,Coca A,Luque-Otero M

    更新日期:1999-12-01 00:00:00

  • Evaluating interventions to reduce central aortic pressure, arterial stiffness and morbidity--mortality.

    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


    authors: Williams B

    更新日期:2012-06-01 00:00:00

  • Arterial hypertension due to occlusion of the adrenal vein in the rat is strain-dependent.

    abstract:OBJECTIVE:To determine whether the development of arterial hypertension due to occlusion of the central adrenal vein in the rat is strain-dependent DESIGN AND METHODS:The experiments were performed on male rats weighing 300-400 g each, of the following strains: Wistar outbred, Wistar Glaxo, Lewis, Wistar-Kyoto (WKY) r...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Abramczyk P,Lisiecka A,Papierski K,Ziecina R,Przybylski J

    更新日期:1998-09-01 00:00:00

  • Real-world evidence of suboptimal blood pressure control in patients with type 2 diabetes.

    abstract:AIMS:In order to eventually improve blood pressure (BP) management, the aim of this study was to identify subgroups of type 2 diabetes mellitus (T2DM) patients with distinct trajectories of SBP levels. Identifying subgroups with distinct SBP trajectories helps to better understand the course of SBP levels in T2DM patie...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Walraven I,Mast MR,Hoekstra T,Jansen AP,Rauh SP,Rutters FR,van der Heijden AA,Elders PJ,Moll AC,Polak BC,Dekker JM,Nijpels G

    更新日期:2015-10-01 00:00:00

  • Angiotensin converting enzyme inhibition prevents proto-oncogene expression in the vascular wall after injury.

    abstract:OBJECTIVES:Angiotensin converting enzyme (ACE) inhibitors reduce neointimal hyperplasia after balloon denudation, but the mechanisms are not completely understood. It has been demonstrated that nuclear oncogenes are induced in the vascular wall in the hours immediately after injury, and that the same genes are induced ...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Van Belle E,Bauters C,Wernert N,Delcayre C,McFadden EP,Dupuis B,Lablanche JM,Bertrand ME,Swynghedauw B

    更新日期:1995-01-01 00:00:00

  • Impairment of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas axis contributes to the acceleration of two-kidney, one-clip Goldblatt hypertension.

    abstract:OBJECTIVE:Recent studies have shown that the heptapeptide angiotensin-(1-7) [Ang-(1-7)] exerts important vasoactive actions and can act as an endogenous physiological antagonist of angiotensin II (Ang II) within the renin-angiotensin system (RAS). The present study was performed to evaluate the effects, first, of chron...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Bürgelová M,Vanourková Z,Thumová M,Dvorák P,Opocenský M,Kramer HJ,Zelízko M,Malý J,Bader M,Cervenka L

    更新日期:2009-10-01 00:00:00

  • Influence of the endothelial nitric oxide synthase gene on conventional and ambulatory blood pressure: sib-pair analysis and haplotype study.

    abstract:BACKGROUND:Nitric oxide is involved in the regulation of vascular basal tone and blood pressure. Polymorphisms of NOS3, the gene that codes for endothelial nitric oxide synthase, have been associated with essential hypertension. OBJECTIVE:To look for linkage and association of three di-allelic polymorphisms (Glu298Asp...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Persu A,Vinck WJ,El Khattabi O,Janssen RG,Paulussen AD,Devuyst O,Vlietinck R,Fagard RH

    更新日期:2005-04-01 00:00:00

  • Adaptive immune disorders in hypertension and heart failure: focusing on T-cell subset activation and clinical implications.

    abstract::: Hypertension is a growing health concern worldwide. Established hypertension is a causative factor of heart failure, which is characterized by increased vascular resistance and intractable uncontrolled blood pressure. Hypertension and heart failure have multiple causes and complex pathophysiology but cellular immuni...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Rai A,Narisawa M,Li P,Piao L,Li Y,Yang G,Cheng XW

    更新日期:2020-10-01 00:00:00

  • Persistence of baroreceptor control of cerebral blood flow velocity at a simulated altitude of 5000 m.

    abstract:OBJECTIVE:To assess the effects of acute exposure to simulated high altitude on baroreflex control of mean cerebral blood flow velocity (MCFV). PATIENTS AND METHODS:We compared beat-to-beat changes in RR interval, arterial blood pressure, mean MCFV (by transcranial Doppler velocimetry in the middle cerebral artery), e...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Passino C,Cencetti S,Spadacini G,Quintana R,Parker D,Robergs R,Appenzeller O,Bernardi L

    更新日期:2007-09-01 00:00:00

  • Very low frequency blood pressure variability is modulated by myogenic vascular function and is reduced in stroke-prone rats.

    abstract:BACKGROUND:Cerebrovascular myogenic function, which protects the brain from hemorrhagic stroke, is impaired in stroke-prone spontaneously hypertensive rats. Furthermore, myogenic function contributes to very low frequency blood pressure variability and dynamic autoregulation of cerebral blood flow is most effective at ...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Stauss HM,Petitto CE,Rotella DL,Wong BJ,Sheriff DD

    更新日期:2008-06-01 00:00:00

  • Renal vascular resistance properties and glomerular protection in early established SHR hypertension.

    abstract:OBJECTIVE:To characterize the in vivo vascular properties of the spontaneously hypertensive rat (SHR) renal vascular bed by examining vascular conductance/resistance responsiveness to vasoactive agents in vivo and determining whether the filtration surface area of glomerular capillaries is reduced. DESIGN AND METHODS:...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Kett MM,Bergström G,Alcorn D,Bertram JF,Anderson WP

    更新日期:2001-08-01 00:00:00

  • Glomerular hemodynamics and arterial function in normal individuals.

    abstract:OBJECTIVE:To determine the relationship between arterial function (stiffness and wave reflection) and glomerular hemodynamics. METHODS:In 49 healthy normotensive individuals, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by urinary clearances of 99mTC-DTPA and 131I-hippuran, res...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Fesler P,du Cailar G,Ribstein J,Mimran A

    更新日期:2010-12-01 00:00:00

  • Pressor responses to laboratory stresses and daytime blood pressure variability.

    abstract::We studied 56 patients with essential hypertension to determine whether responses to standardized laboratory mental and physical challenges accurately reflect blood pressure variability during routine daily activities. Four activities were performed in the laboratory: mental arithmetic, a reaction time test, isometric...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Floras JS,Hassan MO,Jones JV,Sleight P

    更新日期:1987-12-01 00:00:00

  • Relationship between blood pressure, cholesterolemia and serum apolipoprotein B in a large population sample: the Brisighella Heart Study.

    abstract:OBJECTIVE:The objective is to evaluate the relationship between cholesterolemia, serum apolipoprotein B (apoB) level and blood pressure in a large sample of general population. METHODS:The Brisighella Heart Study (BHS) is a prospective, population-based longitudinal epidemiological investigation. For this study, we an...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Cicero AF,D'Addato S,Veronesi M,Rosticci M,Santi F,Dormi A,Borghi C,Brisighella Heart Study Group.

    更新日期:2012-03-01 00:00:00

  • Mediation of the vasoactive properties of diadenosine tetraphosphate via various purinoceptors.

    abstract:OBJECTIVE AND METHODS:The vasoactive properties of P1,P4-diadenosine tetraphosphate (Ap4A) were studied by measuring the effects of perfusion pressure of a rat isolated perfused kidney. RESULTS:The vasoconstrictive response to Ap4A was mediated to a large extent to a P2X receptor which could be shown by inhibition wit...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: van der Giet M,Jankowski J,Schlüter H,Zidek W,Tepel M

    更新日期:1998-12-01 00:00:00

  • Blood pressure is the major driving force for plaque formation in aortic-constricted ApoE-/- mice.

    abstract:OBJECTIVE:Using an aortic constriction model in mice, we studied whether the increase in pressure or the activation of the renin-angiotensin system (RAS) and its main receptors is the main driving force for plaque progression. METHODS:Male ApoE mice underwent sham surgery or placement of a suprarenal silver clip aroun...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Johansson ME,Wickman A,Skøtt O,Gan LM,Bergström G

    更新日期:2006-10-01 00:00:00

  • Improvement of renal dysfunction in rats with chronic heart failure after myocardial infarction by treatment with the endothelin A receptor antagonist, LU 135252.

    abstract:OBJECTIVE:To investigate the role of an activated endothelin system in the renal dysfunction observed in chronic heart failure after myocardial infarction. METHODS:In rats with heart failure after myocardial infarction and in sham-operated animals (Sham), we investigated the effect on renal function of long-term oral ...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Bauersachs J,Braun C,Fraccarollo D,Widder J,Ertl G,Schilling L,Kirchengast M,Rohmeiss P

    更新日期:2000-10-01 00:00:00

  • Prediction of high blood pressure in young people: the limited usefulness of parental blood pressure data.

    abstract::Blood pressure was measured in 864 young people aged 16-24 years, 8 years after both of their parents had their blood pressures measured as part of the screening phase of the Medical Research Council Mild Hypertension Trial. Only 29% of offspring with a conventional 'family history of hypertension', defined in terms o...

    journal_title:Journal of hypertension

    pub_type: 临床试验,杂志文章


    authors: Watt GC,Foy CJ,Holton DW,Edwards HE

    更新日期:1991-01-01 00:00:00

  • Supporting self-management for people with hypertension: a meta-review of quantitative and qualitative systematic reviews.

    abstract:OBJECTIVES:Globally, healthcare policy promotes supported self-management as a strategy for people with long-term conditions. This meta-review aimed to explore how people with hypertension make sense of their condition, to assess the effectiveness of supported self-management in hypertension, and to identify effective ...

    journal_title:Journal of hypertension

    pub_type: 杂志文章,评审


    authors: Shahaj O,Denneny D,Schwappach A,Pearce G,Epiphaniou E,Parke HL,Taylor SJC,Pinnock H

    更新日期:2019-02-01 00:00:00

  • Mortality in patients who have their antihypertensive therapy changed.

    abstract::Medical records were examined for 1935 patients who presented sequentially to a hypertension clinic between 1971 and 1981. Patients were classified according to whether they were on a beta-blocker, methyldopa, a potassium-losing diuretic, or whether they had discontinued any of these treatments. Age-standardized morta...

    journal_title:Journal of hypertension

    pub_type: 杂志文章


    authors: Franks PJ,Hartley K,Bulpitt PF,Bulpitt CJ,Dollery CT

    更新日期:1989-07-01 00:00:00