Paradoxical effects of iron chelation on growth of vascular endothelial cells.

Abstract:

:Endothelial cell (EC) and vascular smooth muscle cell (VSMC) interactions play critical roles in restenosis following vascular injury. We examined the effects of intracellular iron chelation on endothelial cell cycle progression and VSMC modulation of endothelial cell growth. A diffusible, lipid-soluble iron chelator that rapidly enters cells, desferri-exochelin 772SM (D-Exo), was studied in human endothelial cells and VSMCs. In both cell types D-Exo reversibly halted cell cycle progression from G0/G1 phase to S phase and from S phase to G2/M phase and increased expression of hypoxia-inducible factor 1alpha (HIF-1alpha). D-Exo increased secretion of vascular endothelial growth factor (VEGF), a downstream target of HIF-1alpha, in VSMCs, but there was no VEGF production in endothelial cells. D-Exo was 25-fold more potent than the lipid-insoluble iron chelator deferoxamine, which does not readily enter cells. Intracellular iron chelation with D-Exo directly inhibits endothelial cell growth but indirectly stimulates endothelial cell growth by increasing VEGF release by VSMCs.

journal_name

J Cardiovasc Pharmacol

authors

Hodges YK,Reese SM,Pahl PM,Horwitz LD

doi

10.1097/01.fjc.0000159659.78675.4a

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

539-44

issue

6

eissn

0160-2446

issn

1533-4023

pii

00005344-200506000-00007

journal_volume

45

pub_type

杂志文章
  • Alpha-adrenoreceptor blockade with indoramin in hypertension.

    abstract::We have evaluated the effects of indoramin, an alpha-adrenoreceptor blocking drug, used as sole therapy in a group of 27 patients with essential hypertension. Blood pressure and heart rate were measured continuously over prolonged ambulatory periods using an established invasive technique before and after six weeks of...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00005344-198305000-00001

    authors: Gould BA,Mann S,Davies AB,Altman DG,Raftery EB

    更新日期:1983-05-01 00:00:00

  • Characterization of endothelin-1 stimulation of catecholamine release from adrenal chromaffin cells.

    abstract::Addition of endothelin-1 (ET-1) to primary cultures of bovine adrenal chromaffin cells causes a significant enhancement of norepinephrine and epinephrine efflux, with an EC50 of about 1 nM. A maximally effective concentration of endothelin (10 nM) gives a transient increase in noradrenaline release within 5 min. The a...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198900135-00066

    authors: Boarder MR,Marriott DB

    更新日期:1989-01-01 00:00:00

  • Plasma endothelin-1 in hemodialysis treatment - the influence of hypertension.

    abstract::In patients on chronic hemodialysis hypotensive episodes are frequently encountered during the course of treatment and the prevalence of atherosclerosis is increased. Endothelin-1 (ET-1), an endothelium-derived peptide with vasoconstrictive and mitogenic effects on smooth muscles, is involved in vascular tone regulati...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/01.fjc.0000166215.50415.36

    authors: Stefanidis I,Wurth P,Mertens PR,Ikonomov V,Philippidis G,Golphinopoulos S,Makropoulos V,Liakopoulos V,Mann H,Heintz B

    更新日期:2004-11-01 00:00:00

  • Renal and depressor effects of SQ 29,072, a neutral endopeptidase inhibitor, in conscious hypertensive rats.

    abstract::The depressor and renal responses to the neutral endopeptidase (NEP) inhibitor, SQ 29,072, were characterized in both the conscious spontaneously hypertensive rat (SHR) and the conscious deoxycorticosterone acetate (DOCA)/salt hypertensive rat. Inhibition of tissue NEP activity by pharmacologically active doses was al...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199007000-00022

    authors: Seymour AA,Norman JA,Asaad MM,Fennell SA,Swerdel JN,Little DK,Dorso CR

    更新日期:1990-07-01 00:00:00

  • Pharmacodynamic effect of nicardipine on left ventricular function in systemic sclerosis.

    abstract::Left ventricular dysfunction in systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance in coronary microcirculation. We evaluated the pharmacodynamic effect of the calcium channel blocker nicardipine on left ventricular function assessed by radionuclide ventriculography in 20 patients wit...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199002000-00011

    authors: Kahan A,Devaux JY,Amor B,Menkès CJ,Weber S,Guérin F,Venot A,Strauch G

    更新日期:1990-02-01 00:00:00

  • Cardiac and vascular beta-adrenoceptor-mediated responses before and during treatment with bisoprolol or atenolol.

    abstract::The degree of cardiac and vascular beta-adrenoceptor blockade of bisoprolol and atenolol was determined by the chronotropic dose 25 (CD25) of isoproterenol (the dose of an intravenous isoproterenol bolus required to increase resting heart rate by 25 beats/min) and by the increase in forearm blood flow (venous occlusio...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1097/00005344-198511001-00010

    authors: Bolli P,Müller FB,Linder L,Ji BH,Bühler FR

    更新日期:1986-01-01 00:00:00

  • S-equol Partially Restored Endothelial Nitric Oxide Production in Isoflavone-deficient Ovariectomized Rats.

    abstract:BACKGROUND:S-equol is known as an estrogenic substance, but its ability to restore vascular endothelial function is unknown. The aim of this study was to investigate the impact of S-equol on endothelial function and intimal thickening under isoflavone- and estrogen-deficient circumstances. METHODS:Twelve-week-old fema...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0000000000000220

    authors: Ohkura Y,Obayashi S,Yamada K,Yamada M,Kubota T

    更新日期:2015-05-01 00:00:00

  • Nicorandil but not ISDN upregulates endothelial nitric oxide synthase expression, preventing left ventricular remodeling and degradation of cardiac function in Dahl salt-sensitive hypertensive rats with congestive heart failure.

    abstract::Cardiac endothelial nitric oxide synthase (ecNOS) was suppressed and inducible NOS (iNOS) enhanced at the decompensated heart failure stage in 18-week-old Dahl salt-sensitive (DS) hypertensive rats to which a high-salt diet had been administered from the age of 6 weeks. Nicorandil (NIC) enhanced ecNOS by activating Ad...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/01.fjc.0000211741.47960.c2

    authors: Horinaka S,Kobayashi N,Yagi H,Mori Y,Matsuoka H

    更新日期:2006-05-01 00:00:00

  • Antihypertensive drug treatment in elderly hypertensive subjects: evidence of protection.

    abstract::The different intervention trials in elderly hypertensive subjects are compatible with the hypothesis that antihypertensive drug treatment decreases cardiovascular mortality, mainly by a reduction of cerebrovascular mortality. Antihypertensive drug treatment in elderly hypertensive subjects also leads to a decrease in...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:

    authors: Staessen J,Fagard R,Van Hoof R,Amery A

    更新日期:1988-01-01 00:00:00

  • Effects of exercise and other nonpharmacological measures on blood pressure and cardiac hypertrophy.

    abstract::Reversal of left ventricular hypertrophy (LVH) is an important target of antihypertensive therapy. Nonpharmacological approaches such as weight reduction and exercise training have favorable effects on other risk factors. However, there are few data on their effects on LVH. Athletes have eccentric rather than concentr...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1097/00005344-199117002-00015

    authors: Jennings G,Dart A,Meredith I,Korner P,Laufer E,Dewar E

    更新日期:1991-01-01 00:00:00

  • Probucol reduces myocardial dysfunction during reperfusion after short-term ischemia in rabbit heart.

    abstract::The effects of probucol, a lipophilic antioxidant, on the myocardial dysfunction (stunning) observed during reperfusion after 15-min ischemia in rabbit heart were studied. Rabbits received food with or without 1% probucol for 3 weeks. They were then anesthetized and prepared for recording of myocardial segment shorten...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199101000-00023

    authors: Dage RC,Anderson BA,Mao SJ,Koerner JE

    更新日期:1991-01-01 00:00:00

  • Controlled multicenter study with quinapril, hydrochlorothiazide, and combination in patients with moderate to severe hypertension.

    abstract::In an 8-week, double-blind, randomized, active-controlled, multicenter study with three parallel treatment groups, we compared the efficacy and safety of once-daily 20 mg quinapril plus 12.5 mg hydrochlorothiazide (HCTZ) with each drug as monotherapy in patients with moderate to severe hypertension. Hypertensive out-p...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1097/00005344-199507000-00018

    authors: Romero R,Castellote E,Ocón J,Wagner B

    更新日期:1995-07-01 00:00:00

  • The effects of age on the pharmacodynamics and pharmacokinetics of two formulations of verapamil.

    abstract::The present study, undertaken in general practice, was designed to evaluate the effects of age on the pharmacodynamics and pharmacokinetics of a conventional and a slow-release formulation (Securon SR) of verapamil. Two groups of 12 patients with essential hypertension were treated in an open, randomized, crossover st...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00005344-198900134-00017

    authors: Hosie J,Hosie G,Meredith PA

    更新日期:1989-01-01 00:00:00

  • Monophosphoryl lipid A: a novel nitric oxide-mediated therapy to attenuate platelet thrombosis?

    abstract::Nitric oxide (NO) is a potent inhibitor of platelet aggregation. However, the benefits of NO-based therapies can be confounded by concomitant hypotension. Monophosphoryl lipid A (MLA) is a nontoxic derivative of endotoxin that purportedly increases nitric oxide synthase (NOS) activity and, presumably, NO production, y...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200003000-00004

    authors: Przyklenk K,Hata K,Whittaker P,Elliott GT

    更新日期:2000-03-01 00:00:00

  • Inotropic Effects of Prostacyclins on the Right Ventricle Are Abolished in Isolated Rat Hearts With Right-Ventricular Hypertrophy and Failure.

    abstract:BACKGROUND:Prostacyclin mimetics are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostanoids on right-ventricular (RV) function are unknown. We aimed to investigate the direct effects of prostacyclin mimetics on RV function in hearts with and without RV hypertroph...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0000000000000435

    authors: Holmboe S,Andersen A,Johnsen J,Nielsen JM,Nørregaard R,Bøtker HE,Clapp LH,Nielsen-Kudsk JE

    更新日期:2017-01-01 00:00:00

  • Endothelial function, nitric oxide, and cocoa flavanols.

    abstract::Endothelial dysfunction is the pathophysiologic principle involved in the initiation and progression of arteriosclerosis, thus endothelial function serves as a "barometer" for cardiovascular health that can be used for the evaluation of new therapeutic strategies. This review provides an introduction to the concept of...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1097/00005344-200606001-00007

    authors: Heiss C,Schroeter H,Balzer J,Kleinbongard P,Matern S,Sies H,Kelm M

    更新日期:2006-01-01 00:00:00

  • Two weeks of intermittent dobutamine therapy restores cardiac performance and inotropic responsiveness in conscious rats with heart failure.

    abstract::Dobutamine is frequently used for acute therapy in heart failure. In the present study, the hemodynamic effects of long-term intermittent dobutamine therapy were investigated in conscious rats with heart failure. Rats with healed myocardial infarctions received two i.p. injections of dobutamine per day for 2 weeks. He...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199106000-00014

    authors: Schoemaker RG,Debets JJ,Struyker-Boudier HA,Smits JF

    更新日期:1991-06-01 00:00:00

  • Effects of captopril on limiting infarct size in conscious dogs.

    abstract::The effects of angiotensin-converting enzyme inhibitor captopril on infarct size and cardiovascular hemodynamics were studied in 35 conscious dogs subjected to 24 h of coronary occlusion. Following occlusion of the left anterior descending coronary artery, 10 dogs were infused with captopril 0.25 mg/kg/h i.v. (group 1...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Daniell HB,Carson RR,Ballard KD,Thomas GR,Privitera PJ

    更新日期:1984-11-01 00:00:00

  • ACE inhibition but not angiotensin II antagonism reduces plasma fibrinogen and insulin resistance in overweight hypertensive patients.

    abstract::The aim of this study was to compare the effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril and the angiotensin II antagonist losartan on insulin sensitivity and plasma fibrinogen in overweight hypertensive patients. Twenty-eight overweight mild to moderate [diastolic blood pressure (DBP) >90 and...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00005344-199810000-00014

    authors: Fogari R,Zoppi A,Lazzari P,Preti P,Mugellini A,Corradi L,Lusardi P

    更新日期:1998-10-01 00:00:00

  • Relaxations to endothelium-derived relaxing factor and the metabolite of molsidomine, SIN-1, in the aorta and the hindquarters of the rat.

    abstract::The effects of SIN-1 were studied on isolated aortic rings and perfused hindquarters of the rat and were compared with the effects of nitroglycerin and endothelium-derived relaxing factor (EDRF) released by acetylcholine or histamine (aorta) and carbachol (hindquarters). SIN-1 relaxes rat aortic rings in a dose-depend...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Van de Voorde J,Claeys M,Leusen I

    更新日期:1989-01-01 00:00:00

  • Altered intra- and extraluminal effects of 5-hydroxytryptamine in hypertensive mesenteric resistance arteries: contribution of the endothelium and smooth muscle.

    abstract::Vasoconstrictor responses to intraluminal and extraluminal 5-hydroxytryptamine (5-HT) were studied in isolated mesenteric resistance arteries of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Third-order branches of mesenteric arteries were dissected free and mounted on glass cannulae in organ cha...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199108000-00015

    authors: Dohi Y,Lüscher TF

    更新日期:1991-08-01 00:00:00

  • Different potency of endothelium-derived relaxing factors against thromboxane, endothelin, and potassium chloride in intramyocardial porcine coronary arteries.

    abstract::Endothelium-derived relaxing factors (EDRFs) and prostacyclin (PGI2) released from endothelial cells are potent vasodilators; endothelin-1 and thromboxane A2 may be their physiological antagonists. Interactions between these vasodilators and vasoconstrictors were studied in isolated intramyocardial porcine coronary ar...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199107000-00016

    authors: Noll G,Bühler FR,Yang Z,Lüscher TF

    更新日期:1991-07-01 00:00:00

  • Physical activity and the metabolic cardiovascular syndrome.

    abstract::Hyperinsulinemia, lipid abnormalities, and impaired fibrinolytic capacity may accompany hypertension, and comprise the metabolic cardiovascular syndrome. They are all independent risk factors for coronary artery disease. Lifestyle modifications can reduce the coronary artery risk. Physical activity has been shown to i...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:

    authors: Westheim A,Os I

    更新日期:1992-01-01 00:00:00

  • Neutrophil degranulation related to the reperfusion of ischemic human heart during cardiopulmonary bypass.

    abstract::Activation of polymorphonuclear neutrophils (PMNs) during cardiopulmonary bypass (CPB) is a wellknown phenomenon. This study aimed to determine if activated PMNs are sequestered and degranulated within the myocardium at reperfusion in patients undergoing coronary artery bypass grafting (CABG). Nineteen patients underg...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00005344-199500252-00026

    authors: Dhôte-Burger P,Vuilleminot A,Lecompte T,Pasquier C,Bara L,Julia P,Chardigny C,Fabiani JN

    更新日期:1995-01-01 00:00:00

  • Pathophysiology of diabetic nephropathy: involvement of multifaceted signalling mechanism.

    abstract::Diabetic nephropathy is a major cause of end-stage renal failure and the mortality rate due to this disease is continuously progressing worldwide. The multifaceted signalling mechanisms have been identified to be involved in the pathogenesis of diabetic nephropathy. Despite the modern therapies like antidiabetics, ant...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1097/FJC.0b013e3181ad2190

    authors: Balakumar P,Arora MK,Reddy J,Anand-Srivastava MB

    更新日期:2009-08-01 00:00:00

  • Chronic treatment after acute myocardial infarction: which drug for which patient? Nitrates.

    abstract::Nitrates are beneficial in post-myocardial infarction patients with stable, unstable, and Prinzmetal's variant angina and as adjunctive therapy in congestive heart failure. They are available in multiple formulations that differ in chemical structure, pharmacokinetics, onset and duration of activity, and peak effect; ...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:

    authors: Scardi S

    更新日期:1989-01-01 00:00:00

  • Possible mechanism of the vasodepressor effect of endokinin a/b in anesthetized rats.

    abstract::We investigated the mechanism of the vasodepressor effect of endokinin A/B. An intravenous (IV) bolus of endokinin A/B (0.05-0.3 nmol/kg) dose-dependently decreased mean arterial pressure in thiobutabarbital-anesthetized rats. The magnitude of the response was unaffected by IV pretreatment with NG-nitro-L-arginine met...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/01.fjc.0000175236.41573.2a

    authors: Abdelrahman AM,Syyong H,Tjahjadi A,Pang CC

    更新日期:2005-09-01 00:00:00

  • Effects of the acylcarnitine-transferase blocking agent sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) on metabolism and regional function in the underperfused canine myocardium.

    abstract::We investigated the effects of sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) on regional myocardial function and metabolism in anesthetized, thoracotomized dogs subjected to a 53.5% reduction in flow through the circumflex branch of the left coronary artery (LCX). Regional function in the area suppl...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198503000-00011

    authors: Seitelberger R,Kraupp O,Winkler M,Brugger G,Raberger G

    更新日期:1985-03-01 00:00:00

  • Effects on autonomic function of a new angiotensin converting enzyme inhibitor, ramipril.

    abstract::To investigate the effects of ramipril, a new angiotensin converting enzyme inhibitor, on autonomic function, autonomic function tests were performed in eight healthy male subjects, aged 22-26 years, after single oral administration of 5 mg of ramipril or placebo, in a randomized, double-blind, crossover design. Measu...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00005344-198900133-00010

    authors: Sugimoto K,Kumagai Y,Tateishi T,Seguchi H,Ebihara A

    更新日期:1989-01-01 00:00:00

  • Endothelin-secreting tumor.

    abstract::Recently, we have reported two cases with endothelin (ET)-secreting tumor presenting with hypertension and elevated plasma endothelin-1 (ET-1) levels. The present study examines the histopathology of the ET-secreting tumor in one of these cases. The neoplasm was located in the skin and microscopically characterized as...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199100177-00111

    authors: Yokokawa K,Tahara H,Kohno M,Murakawa K,Yasunari K,Nakagawa K,Hamada T,Otani S,Yanagisawa M,Takeda T

    更新日期:1991-01-01 00:00:00