Abstract:
:In previous studies, it was demonstrated that lipid core nanoparticles (LDE) resemble the low-density lipoprotein structure and carrying the antiproliferative agent paclitaxel (PTX) strongly reduced atherosclerosis lesions induced in rabbits by cholesterol feeding. Currently, the aim was to verify whether combining LDE-PTX treatment with methotrexate (MTX) associated with LDE (LDE-MTX) could accelerate the atherosclerosis regression attained with single LDE-PTX treatment, after withdrawing the cholesterol feeding. Thirty-eight rabbits were fed 1% cholesterol chow for 8 weeks. Six of these rabbits were then euthanized for analyses of the aorta (controls). In the remaining rabbits, cholesterol feeding was withdrawn, and those 32 animals were allocated to 3 groups submitted to different 8-week intravenous treatments, all once/week: LDE-PTX (n = 10; 4 mg/kg), LDE-PTX + LDE-MTX (n = 11; 4 mg/kg), and LDE-alone (n = 11). Rabbits were then euthanized and aortas were excised for morphometric, immunohistochemical, and gene expression analyses. After cholesterol feeding withdrawal, in comparison with LDE-alone group, both LDE-PTX and LDE-PTX + LDE-MTX treatments had the ability to increase the regression of plaque areas: -49% in LDE-PTX and -59% for LDE-PTX + LDE-MTX. However, only LDE-PTX + LDE-MTX treatment elicited reduction in the intima area, estimated in -57%. Macrophage presence in aortic lesions was reduced 48% by LDE-PTX and 43% by LDE-PTX + LDE-MTX treatment. Matrix metalloproteinase 9 was reduced by either LDE-PTX (74%) or LDE-PTX + LDE-MTX (78%). Tumor necrosis factor α gene expression was reduced 65% by LDE-PTX and 79% by LDE-PTX + LDE-MTX. In conclusion, treatment with LDE-PTX indeed accelerated plaque reduction after cholesterol feeding; LDE-PTX + LDE-MTX further increased this effect, without any observed toxicity. These results pave the way for the use of combined chemotherapy to achieve stronger effects on aggravated, highly inflamed atherosclerotic lesions.
journal_name
J Cardiovasc Pharmacol Therjournal_title
Journal of cardiovascular pharmacology and therapeuticsauthors
Gomes FLT,Maranhão RC,Tavares ER,Carvalho PO,Higuchi ML,Mattos FR,Pitta FG,Hatab SA,Kalil-Filho R,Serrano CV Jrdoi
10.1177/1074248418778836subject
Has Abstractpub_date
2018-11-01 00:00:00pages
561-569issue
6eissn
1074-2484issn
1940-4034journal_volume
23pub_type
杂志文章abstract:OBJECTIVE:To investigate the effect of a pharmacist care program on cardiovascular risks in type 2 diabetic patients. METHODS:A 9-month, prospective, randomized, controlled study was conducted in a public hospital in Hong Kong. Patients in the intervention group had regular drug-counseling sessions with pharmacists in...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1177/1074248410396216
更新日期:2012-03-01 00:00:00
abstract::BACKGROUND: Micropuncture studies were performed to determine the intrarenal hemodynamic effects of two conventional antihypertensive agents, hydrochlorothiazide (HCTZ) and hydralazine (HYDR) alone and in combination. METHODS AND RESULTS: Male spontaneously hypertensive and normotensive Wistar Kyoto rats (19 weeks old...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849600100109
更新日期:1996-01-01 00:00:00
abstract::α-Lipoic acid (LA) has been shown to offer protection against ischemia-reperfusion injury (IRI) in multiple organ systems. N-[(R)-1,2-dithiolane-3-pentanoyl]-L-glutamyl-L-alanine (CMX-2043), a novel analogue of LA, was studied as part of a preclinical development program intended to identify safe and efficacious drug ...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248416640118
更新日期:2016-11-01 00:00:00
abstract::Despite initial promising reports that anti-inflammatory properties of cycloxygenase-2 (COX-2) inhibitors may confer anti-atherosclerosis effects and stabilize the atherosclerotic plaque, subsequent data from long-term clinical trials have shown that selective COX-2 inhibitors are associated with increased risk of car...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/1074248407301172
更新日期:2007-06-01 00:00:00
abstract::BACKGROUND: The effects of sotalol on the 24-hour profile of the QT interval relative to that of the heart rate (HR) may be helpful in determining the time course of the drug's action in controlling cardiac arhythmias. This has not been previously determined. Thus, the objective of the current study was to evaluate th...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849900400104
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND:Fluvastatin is an inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, effectively lowering serum cholesterol concentrations. A high-performance liquid chromatography (HPLC) assay was developed that determined the pharmacokinetics of fluvastatin in healthy individuals after administrat...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 临床试验,杂志文章
doi:10.1177/107424840100600205
更新日期:2001-04-01 00:00:00
abstract::BACKGROUND: The tendency for the electrophysiologic effect of class III antiarrhythmic agents (action potential prolongation) to be diminished at faster heart rates represents a major drawback of this class of drug and is usually referred to as "reverse use dependence." A novel class III agent, MS-551, has recently be...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849700200105
更新日期:1997-01-01 00:00:00
abstract:INTRODUCTION:Recent evidence suggests that transcriptional reprogramming is involved in the pathogenesis of cardiac remodeling (cardiomyocyte hypertrophy and fibrosis) and the development of heart failure. 5-Azacytidine (5aza), an inhibitor of DNA methylation approved for hematological malignancies, has previously demo...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248420979235
更新日期:2020-12-02 00:00:00
abstract::Effects of therapy with the potassium-channel opener and vasodilator nicorandil were studied in reperfused infarction of hypertrophied hearts by using magnetic resonance imaging (MRI), hemodynamic measurements, and histochemical staining. Aortic banding was performed on 22 Sprague-Dawley rats to induce left ventricula...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424840400900307
更新日期:2004-09-01 00:00:00
abstract:BACKGROUND:We hypothesized that the cardioprotective effect of angiotensin II (AngII) type 1 receptor (AT(1)R) blockade during in vivo ischemia-reperfusion (IR) might be associated with an increase in AngII type 2 receptor (AT(2)R) protein, as well as 1,4,5-inositol trisphosphate type 2 receptor (IP(3)R) and protein ki...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1054/JCPT.2000.19245
更新日期:2000-10-01 00:00:00
abstract::Antiplatelet therapy is indicated for the treatment of ischemic stroke or transient ischemic attack (TIA). Aspirin reduces subsequent occlusive vascular events, including recurrent stroke, by about 25%. In such patients, clopidogrel has been evaluated in an effort to further reduce risk. In the Management of Atherothr...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/1074248406296862
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:Low levels of 25-hydroxyvitamin D (25(OH)VitD) have been recognized as an emerging cardiovascular disease (CVD) risk factor. Statins are reported to increase 25(OH)VitD concentration. Animal studies suggest that ezetimibe is a moderate inhibitor of intestinal 25(OH)VitD absorption, but its effect in humans i...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1177/1074248412470513
更新日期:2013-05-01 00:00:00
abstract::Data obtained in both preclinical models and humans have revealed that the favorable cardiac consequences of ischemic conditioning extend beyond a direct effect on the cardiomyocyte. In the current review, we summarize our as-yet limited understanding of the complex relationships between ischemic conditioning, platele...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/1074248417724871
更新日期:2017-09-01 00:00:00
abstract::Low-molecular-weight heparins (LMWHs) endure as important drugs for thromboprophylaxis. Although clinical use relies on the subcutaneous (SC) route, our previous studies show that single-dose orally administered LMWHs have antithrombotic activity. Since thromboprophylaxis requires long-term treatment, we examined anti...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248416667601
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND:We investigated whether the cardioprotective, volatile gas anesthetic agent, isoflurane, could improve survival and organ function from hemorrhagic shock in an experimental rat model, compared to standard nonvolatile anesthetic agent ketamine/xylazine. METHODS:Sprague Dawley rats (both genders) were randomi...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248420919221
更新日期:2020-07-01 00:00:00
abstract::Dronedarone is a new antiarrhythmic drug for patients with nonpermanent atrial fibrillation (AF). A relatively consistent finding in all trials studying dronedarone was a moderate but significant elevation of serum creatinine. Since dronedarone competes for the same organic cation transporter in the distal renal tubul...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248412453873
更新日期:2013-03-01 00:00:00
abstract::The antiarrhythmic potential of postconditioning in in vivo models remains poorly defined. We compared the effects of pre- and postconditioning on ventricular arrhythmogenesis against controls with and without reperfusion. Wistar rats (n = 40, 269 ± 3 g) subjected to ischemia (30 minutes)--reperfusion (24 hours) were ...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248413482183
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:Hypertension is a major cause of death and morbidity worldwide and is increasing in prevalence. The Renin-angiotensin system (RAS) is the most common mechanism involved in the pathophysiology of hypertension. Understanding the mechanism of the pathophysiologic processes will help direct potential therapeutic...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248419838503
更新日期:2019-09-01 00:00:00
abstract::The primary effect of ischemia is reduced aerobic adenosine triphosphate (ATP) formation in mitochondria. This triggers accelerated glycolysis and reduced cell pH, Ca(2+) accumulation, K(+) efflux, adenosine formation, and the clinical signs of ischemia: chest pain and a shift in the ST segment. Traditional therapies ...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/107424840400900104
更新日期:2004-09-01 00:00:00
abstract::The existing clinical studies on remote ischemic preconditioning in patients undergoing cardiovascular surgery are critically reviewed, with a focus on infarct size reduction and clinical outcome as end points. Confounders, notably the use of propofol anesthesia are identified. The need for better designed trials with...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/1074248416687874
更新日期:2017-07-01 00:00:00
abstract:INTRODUCTION:Pulmonary hypertension (PH) is a potentially deadly disease for infants and adults with few existing medical interventions and no cure. In PH, increased blood pressure in the pulmonary artery eventually leads to heart failure. Fasudil, an antagonist of Rho-kinase, causes vasodilation leading to decreased s...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248418772814
更新日期:2018-09-01 00:00:00
abstract:BACKGROUND:Whether cardioprotection induced by the angiotensin II (AngII) type 2 receptor (AT(2)R) antagonist PD123,319 (PD) after ischemia-reperfusion (IR) is influenced by the concentration of PD, presence of AngII, timing of exposure, or inhibition of proton production from glucose metabolism is not known. METHODS ...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1054/JCPT.2000.7451
更新日期:2000-07-01 00:00:00
abstract:BACKGROUND:Intimal hyperplasia following percutaneous interventional vascular procedures is a major cause of restenosis. Although heparin inhibits intimal hyperplasia, it has not proven clinically useful in part due to an inadequate duration of intramural drug residence. This study was designed to evaluate the efficacy...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424840100600407
更新日期:2001-10-01 00:00:00
abstract::The National Heart, Lung, and Blood Institute convened a Workshop on September 20-21, 2010, "New Horizons in Cardioprotection," to identify future research directions for cardioprotection against ischemia and reperfusion injury. Since the early 1970s, there has been evidence that the size of a myocardial infarction co...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type:
doi:10.1177/1074248411402501
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND:Although a gradual increase in heart rate (HR) during dobutamine stress testing (DST) is desired, few data exists regarding whether this is similarly achieved in patients of widely varying body mass index (BMI). Whether difference in BMI contributes to variation in the hemodynamic and symptomatic response to...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248410384709
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Myocardial hypertrophy is a common clinical finding leading to heart failure and sudden death. Mitofusin 2 (Mfn2), a hyperplasia suppressor protein, is downregulated in hypertrophic heart. This study examined the role of Mfn2 in myocardial hypertrophy and its potential signal pathway. METHODS...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/1074248410385683
更新日期:2011-06-01 00:00:00
abstract::Acute medical illnesses are associated with a prolonged elevation in inflammatory markers that predisposes patients to thrombosis beyond the duration of their hospital stay. In parallel, both observational and randomized data have demonstrated a rate of postdischarge venous thromboembolic events that often exceeds tha...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/1074248415601894
更新日期:2016-05-01 00:00:00
abstract::Platelets are key mediators in the pathophysiology of atherothrombotic disease. Inappropriate platelet activation can lead to thrombosis and ischemic events. Platelet function testing has been used to monitor patient response to antiplatelet therapy. Variability in response to antiplatelet therapy may be due in part t...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章,评审
doi:10.1177/1074248409339309
更新日期:2009-09-01 00:00:00
abstract::BACKGROUND: Conventional microelectrode techniques were used to compare the concentration-dependent effects of vesnarinone (0.1-100 µM) and amrinone (1 µM-1 mM) on action potential duration (APD) and developed force in both isolated dog ventricular trabeculae and Purkinje strands. METHODS AND RESULTS: Both drugs incre...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849600100207
更新日期:1996-04-01 00:00:00
abstract::BACKGROUND: The electrophysiologic mechanisms of the persistence of atrial fibrillation (AF) after its initiation are not well understood. Therefore, the electrophysiologic characteristics of the right atrium were evaluated in an acute, pacing-induced model of AF in the pig in order to identify parameters associated w...
journal_title:Journal of cardiovascular pharmacology and therapeutics
pub_type: 杂志文章
doi:10.1177/107424849900400206
更新日期:1999-04-01 00:00:00