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Biomedical subjects

Massimo Chiariello

Publications and source records attributed to Massimo Chiariello.

At least 37 records · Page 2Linked to original sources
PubMed2005

Stenting and abciximab in primary angioplasty: a review of current status.

Improvement of stent deployment techniques and advances in antiplatelet therapy have shown that stenting in the setting of ST-elevation myocardial infarction (STEMI) is safe and effective. Randomized trials have found that as compared to balloon angioplasty, coronary stenting does not reduce mortality and reinfarction, despite the reduction in target vessel revascularization. Furthermore, these benefits seem to be reduced when applied to unselected patients with STEMI. Direct stenting represents an attractive strategy with potential benefits in terms of myocardial perfusion. Future randomized trials are needed to evaluate if this strategy is associated with a significant impact on outcome, and to provide cost-benefit analysis of an unrestricted use of drug-eluting stent in this high-risk subset of patients. Data from randomized trials have shown that the additional use of abciximab reduces mortality in primary angioplasty. Since the feasibility of long-distance transportation has been shown in several randomized trials, early pharmacological pretreatment may confer further advantages by early recanalization and shorter ischemic time, particularly in high-risk patients. Further large randomized trials are needed to clarify the potential role of small molecules in primary angioplasty for STEMI.

Abciximab↗
PubMed2005

Relationship between brachial artery flow-mediated dilation and coronary flow reserve in patients with peripheral artery disease.

UNLABELLED: The aim of this study was to assess the relationship between brachial artery flow-mediated dilation (FMD) and coronary flow reserve (CFR) in patients with peripheral artery disease (PAD). METHODS: Thirty patients who had PAD, who showed no cardiac symptoms, and who had normal stress SPECT cardiac imaging results and 28 control subjects underwent brachial artery FMD assessment by ultrasound and dipyridamole 99mTc-sestamibi imaging. Myocardial blood flow (MBF) was estimated by measuring first-transit counts in the pulmonary artery and myocardial counts from SPECT images. Estimated CFR was expressed as the ratio of MBF at stress to MBF at rest. RESULTS: Patients with PAD were separated into 2 groups according to the median value of overall FMD (6.85%): group 1 (n=15) with FMD above the median (mean+/-SD, 8.78%+/-1.3%) and group 2 (n=15) with FMD below the median (mean+/-SD, 5.14%+/-0.94%). FMD was significantly higher in control subjects (11.4%+/-3.4%) than in both groups of PAD patients (P<0.001 for both). In control subjects, estimated CFR was 2.2+/-0.4-significantly higher than CFR in both groups of PAD patients (P<0.001 for both). In addition, in PAD patients of group 1, estimated CFR was 1.5+/-0.4-higher than CFR in group 2 (1.0+/-0.4) (P<0.01). When all PAD patients were considered, a significant correlation between FMD and estimated CFR was observed (r=0.56, P<0.005). CONCLUSION: Estimated CFR is significantly lower in patients with PAD than in control subjects, and CFR impairment correlates with the degree of peripheral endothelial dysfunction.

Adult↗
PubMed2005

[Rationale, characteristics and study design of PREAMI (Perindopril and Remodelling in the Elderly with Acute Myocardial Infraction)].

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality and morbidity in patients with heart failure and/or left ventricular systolic dysfunction and in patients with acute myocardial infarction (AMI), especially those with heart failure and/or evidence of left ventricular systolic dysfunction. ACE-inhibitors prevent cardiac events in patients at high cardiovascular risk and/or with documented coronary artery disease. There is a lack of data on the role of ACE-inhibitors in the elderly population with AMI and preserved left ventricular function. Nevertheless, the issue is of primary importance, considering the median age of patients with AMI and heart failure, the high risk of death, heart failure and left ventricular remodeling in the elderly, and the progressive aging of the general population. The multicenter and international (109 centers from five European countries), double-blind, randomized, parallel PREAMI (Perindopril and Remodelling in the Elderly with Acute Myocardial Infarction) trial evaluated the effects of the ACE-inhibitor perindopril in the elderly (aged > or =65 years) with AMI and preserved or mildly depressed left ventricular systolic function (ejection fraction > 40%). The combined primary endpoint was death, hospitalization for heart failure, and left ventricular remodeling (considered as an increase in left ventricular end-diastolic volume > or = 8%). Secondary endpoints included: each single primary endpoint, cardiovascular death, hospitalization for reinfarction or angina, and revascularization. The study involved 1252 patients, with an average age of 73 years, and AMI, treated with recommended usual therapy (antithrombotic drugs, beta-blockers, ACE-inhibitors). After 11 +/- 4 days from AMI, patients were randomized to receive either perindopril (4 mg/day for the first month and 8 mg/day for the remaining 11 months) or placebo, in addition to the recommended conventional therapy. Clinical assessment was performed at fixed times and included two-dimensional echocardiography (to evaluate left ventricular remodeling), Holter electrocardiographic monitoring (to assess heart rate variability and arrhythmias), and blood sampling (for safety evaluation). This review provides details on the background, rationale and study design of PREAMI.

Age Factors↗
PubMed2004

Determinants of atrial fibrillation development in patients with hypertrophic cardiomyopathy.

Predictors of the development of atrial fibrillation (AF) in patients who have hypertrophic cardiomyopathy (HC) have not been extensively studied, although, in these patients, AF contributes to the exacerbation of symptoms and the development of heart failure. The present study determined the role of left atrial (LA) function in the development of AF in patients who have HC. One hundred fifty consecutive patients who had HC, had no history of AF, and who were followed for 5.2 +/- 2.9 years constituted the study population. Using M-mode echocardiography, we measured LA function as global LA fractional shortening and LA diameter. LA volume was measured from 2-dimensional 4-chamber views by the method of disks. During follow-up, 20 patients developed AF. LA function was an independent predictor of AF (odds ratio 0.716, p = <0.001), whereas LA diameter and volume were predictors in addition to age. Kaplan-Meier analysis showed that LA dysfunction carried a high risk of AF. Thus, in patients who have HC, LA function is a strong predictor of AF development and is independent of age.

Adolescent↗
PubMed2004

Aging exacerbates negative remodeling and impairs endothelial regeneration after balloon injury.

Many older patients, because of their high prevalence of coronary artery disease, are candidates for percutaneous coronary interventions (PCI), but the effects of vascular aging on restenosis after PCI are not yet well understood. Balloon injury to the right carotid artery was performed in adult and old rats. Vascular smooth muscle cell (VSMC) proliferation, apoptotic cell death, together with Akt induction, telomerase activity, p27kip1, and endothelial nitric oxide synthase (eNOS) expression was assessed in isolated arteries. Neointima hyperplasia and vascular remodeling along with endothelial cell regeneration were also measured after balloon injury. Arteries isolated from old rats exhibited a significant reduction of VSMC proliferation and an increase in apoptotic death after balloon injury when compared with adult rats. In the vascular wall of adult rats, balloon dilation induced Akt phosphorylation, and this was barely present in old rats. In arteries from old rats, Akt-modulated cell cycle check points like telomerase activity and p27kip1 expression were decreased and increased, respectively, compared with adults. After balloon injury, old rats showed a significant reduction of neointima formation and an increased vascular negative remodeling compared with adults. These results were coupled by a marked delay in endothelial regeneration in aged rats, partially mediated by a decreased eNOS expression and phosphorylation. Interestingly, chronic administration of L-arginine prevented negative remodeling and improved reendothelialization after balloon injury in aged animals. A decreased neointimal proliferation, an impaired endothelial regeneration, and an increase in vascular remodeling after balloon injury were observed in aged animals. The molecular mechanisms underlying these responses seem to be a reduced Akt and eNOS activity.

Aging↗
PubMed2004

Transient and reversible deoxyribonucleic acid damage in human left ventricle under controlled ischemia and reperfusion.

OBJECTIVES: We sought to describe the sequence of molecular events during ischemia and reperfusion of the human heart and to determine the activation of stress kinases and deoxyribonucleic acid (DNA) damage response elements on apoptosis in ischemia or reperfusion of the human heart. BACKGROUND: Brief ischemia is tolerated by cardiac myocytes, but it determines immediate metabolic changes and block of contraction. Prompt restoration of coronary blood flow is inexorably associated with a slow recovery of myocardial contractile function. The prolonged, postischemic contractile dysfunction in the viable tissue is called myocardial stunning. The molecular mechanisms underlying myocardial stunning and ischemia-reperfusion injury are still poorly understood. Their elucidation would be valuable in order to identify novel therapeutic strategies. METHODS: We examined human left ventricular samples taken from 20 patients undergoing elective valve surgery before aortic cross-clamping, 20 +/- 2 min (brief ischemia), 58 +/- 5 min after the cross-clamping period (prolonged ischemia), and 21 +/- 4 min after reconstitution of coronary blood flow (reperfusion). Stress kinases and DNA damage sensor proteins (ATM, H2AX, p53) were determined by immunoblotting with specific antibodies. Electron microscopy analysis was carried out on ischemic and reperfused samples. ATP content, reactive oxygen species (ROS) levels, and cytochrome oxidase activity were determined by biochemical assays. RESULTS: Ischemia caused accumulation of ROS, reduction of cytochrome C oxidase and ATP, and activation of stress kinases p38 and Jun terminal kinase. Electron microscopy showed significant mitochondrial swelling in the majority of cells, but no appreciable apoptosis of cardiomyocytes. During ischemia, myocytes were intensely stained by TUNEL, and many cells showed proliferative cell nuclear antigen-positive nuclei. Finally, we found in ischemic tissues increased p53/p21(WAF) levels and phosphorylation of histone H2AX, a substrate of ATM kinase, which marks double-strand DNA breaks. Reperfusion caused a robust extracellular signal-regulated kinase-1/2 activation, a marked reduction of TUNEL staining, and persistent activation of ATM checkpoint. CONCLUSIONS: These data indicate that ischemia induces extensive DNA damage and activation of ATM checkpoint. Reperfusion allows the repair of the DNA lesions and salvage of ischemic cells.

Adenosine Triphosphate↗
PubMed2004

Tissue factor binding of activated factor VII triggers smooth muscle cell proliferation via extracellular signal-regulated kinase activation.

BACKGROUND: Tissue factor (TF) is the main initiator of coagulation in vivo. Recently, however, a role for TF as a cell receptor involved in signal transduction has been suggested. The aim of the present study was to assess whether activated factor VII (FVIIa) binding to TF could induce smooth muscle cell (SMC) proliferation and to clarify the possible intracellular mechanism(s) responsible for this proliferation. METHODS AND RESULTS: Cell proliferation was induced by FVIIa in a dose-dependent manner, as assessed by [3H]thymidine incorporation and direct cell counting, whereas no response was observed with active site-inhibited FVIIa (FVIIai), which is identical to FVIIa but is devoid of enzymatic activity. Similarly, no proliferation was observed when binding of FVIIa to TF was prevented by the monoclonal anti-TF antibody AP-1. Activation of the p44/42 mitogen-activated protein (MAP) kinase (extracellular signal-regulated kinases 1 and 2 [ERK 1/2]) pathway on binding of FVIIa to TF was demonstrated by transient ERK phosphorylation in Western blots and by suppression of proliferation with the specific MEK (MAP kinase/ERK kinase) inhibitor UO126. ERK phosphorylation was not observed with FVIIai or when cells were pretreated with AP-1. CONCLUSIONS: These data indicate a specific effect by which binding of FVIIa to TF on the surface of SMCs induces proliferation via a coagulation-independent mechanism and possibly indicate a new link between coagulation, inflammation, and atherosclerosis.

Animals↗
PubMed2004

Prevalence, risk factors and cardiovascular comorbidity of symptomatic peripheral arterial disease in Italy.

The epidemiology of peripheral arterial disease (PAD) has been studied almost exclusively in northern European and northern American populations. We report the first survey in Italy to describe the prevalence of symptomatic PAD and clinical correlates. From the lists of seven general practitioners, all subjects aged 40-80 years (n = 4352) received a Rose Questionnaire (RQ). In those reporting pain in the leg while walking, which did not disappear while continuing to walk (n = 760), Doppler examination was performed. PAD was defined by ankle/brachial < or = 0.90, or reduced flow velocity. The prevalence of symptomatic PAD was 1.6% (2.4% in men, 0.9% in women). For each PAD patient, three controls matched for sex and age were randomly selected. At the multivariate analysis, smoking, diabetes and hypertension were significantly associated with PAD. A coexistent cardiovascular disease was found in 34% of patients and 11% of controls (P < 0.001). Only PAD was shown to be independently associated with a previous cardiovascular event. Although symptomatic, 45% of the patients were unaware of their condition. In conclusion, prevalence and cardiovascular comorbidity of symptomatic PAD in Italy seem to be lower than in other western countries. The finding that PAD was unrecognised in about 50% of affected individuals implies that a large proportion of PAD population is not given preventive therapy, so remaining at high cardiovascular risk. Thus, there is need to alert general practitioners to this topic.

Adult↗
PubMed2004

Oleuropein prevents oxidative myocardial injury induced by ischemia and reperfusion.

The potential protective effects of oleuropein, a dietary antioxidant of olive oil, has been investigated in the isolated rat heart. The organs were subjected to 30 minutes of no-flow global ischemia and then reperfused. At different time intervals, the coronary effluent was collected and assayed for creatine kinase activity as well as for reduced and oxidized glutathione. In addition, the extent of lipid peroxidation was evaluated by measuring thiobarbituric acid reactive substance concentration in cardiac muscle. Pretreatment with 20 microg/g oleuropein before ischemia resulted in a significant decrease in creatine kinase and reduced glutathione release in the perfusate. The protective effect of oleuropein against the post-ischemic oxidative burst was investigated by measuring the release, in the coronary effluent, of oxidized glutathione, a sensitive marker of heart's exposure to oxidative stress. Reflow in ischemic hearts was accompanied by a prompt release of oxidized glutathione; in ischemic hearts pretreated with oleuropein, this release was significantly reduced. Membrane lipid peroxidation was also prevented by oleuropein. The reported data provide the first experimental evidence of a direct cardioprotective effect of oleuropein in the acute events that follow coronary occlusion, likely because of its antioxidant properties. This finding strengthens the hypothesis that the nutritional benefit of olive oil in the prevention of coronary heart disease can be also related to the high content of oleuropein and its derivatives. Moreover, our data, together with the well documented antithrombotic and antiatherogenic activity of olive oil polyphenols, indicate these antioxidants as possible therapeutic tools for the pharmacological treatment of coronary heart disease as well as in the case of cardiac surgery, including transplantation.

Animals↗
PubMed2004

Role of semiautomatic defibrillators in a general hospital: "Naples Heart Project".

In Italian hospitals, 85% of patients hospitalized in general medical wards who experience cardiac arrest die, while the incidence is much lower in patients in intensive care units. Defibrillation, in Italian hospitals, often occurs very late, either due to a lack of defibrillators, or due to architectural and structural barriers. The object of an in-hospital emergency service is to prevent and treat cardiac arrest without subsequent complications, such as brain damage, renal failure etc. The Naples Heart Project was based on a feasibility study of the in-hospital emergency service to evaluate and analyze problems associated with type of structure, departmental and institutional dislocation, internal practicability (architectural features and preferential ways), staff numbers and distribution, the calling system for emergency, and the equipment available. The Naples Heart Project began in July 2001, since then it has already created 835 BLSD first responders among the hospital staff; 440 were physicians and physicians still in training, 310 were nurses and 85 were administrative staff.

Automation↗
PubMed2004

Thoracic aortic emergencies: impact of endovascular surgery.

BACKGROUND: Conventional surgery for thoracic aortic emergencies, such as contained or free rupture of thoracic aortic aneurysms, acute type B dissections, and traumatic rupture of the thoracic aorta, is frequently associated with a high rate of mortality and morbidity. To obviate this risk, endovascular surgery is considered to be a valid alternative procedure. METHODS: From March 2001 to July 2002, 15 of 22 patients with acute thoracic aortic syndromes were submitted to endovascular surgery: 3 patients (20%) for traumatic rupture, 4 patients (26.7%) for contained or free rupture of thoracic aortic aneurysm, and 8 patients (53.3%) for acute type B dissection evolving to rupture. Computed tomographic scan was diagnostic in all patients. The stent grafts were introduced through the femoral artery. RESULTS: In the endovascular group there were no perioperative deaths or open conversions. The intraoperative angiography and computed tomographic scan performed on discharge showed no significant endoleaks and successful sealing of the aortic dissection. Average intensive care unit and hospital stay was 1.7 +/- 0.8 and 5.9 +/- 3.0 days. Follow-up ranged between 4 and 23 months and included clinical examinations and serial computed tomographic scan at 3, 6, and 12 months, and every 6 months thereafter. One 84-year-old patient with thoracic aortic aneurysm died of pneumonia 78 days after endovascular surgery. Only one type 1 endoleak was noted in the first patient with traumatic rupture, 3 months after the procedure. CONCLUSIONS: Endovascular surgery is a safe technique, showing encouraging early and midterm results and allowing for prompt treatment of associated lesions in complex multitrauma patients.

Adult↗
PubMed2004

Peripheral arterial disease: the magnitude of the problem and its socioeconomic impact.

Peripheral arterial disease is a common disease in adults and its complications take a great toll in terms of quality of life and treatment costs. As healthcare budgets have taken up more of the economy, and as employers and patients have become concerned about the escalating costs of healthcare, we have entered an era in which individual doctors must become concerned about the costs of a service relative to its benefits. The purpose of this article is to review the literature on the pharmacoeconomics of the diagnostic and therapeutic procedures for peripheral arterial disease. It emerges that peripheral arterial disease places a great burden on healthcare systems and on society as a whole. Some of these costs, including indirect and intangible costs (i.e. those related to lost productivity, and reduced quality of life, respectively) could be reduced if the condition were to be recognized and correctly treated at an early stage.

Arteriosclerosis↗
PubMed2004

[Transthoracic cardioversion in patients with atrial fibrillation: comparison of three different waveforms].

BACKGROUND: Transthoracic electrical cardioversion represents the most effective therapy in converting atrial fibrillation (AF) to sinus rhythm. External cardioverter-defibrillators discharge a current with monophasic and most recently biphasic waveforms. Lately, many articles support the superiority of the biphasic waveform over the monophasic one. Moreover, we have the opportunity to use different biphasic waveforms. The aim of this study was to compare the efficacy (success rate and energy delivered) of a monophasic wave and two different biphasic waves, in patients with persistent AF undergoing external electrical cardioversion. The monophasic wave was delivered by a Zoll M series NM PDMA-9, while the so-called "rectilinear" biphasic waveform was used by a Zoll M series PDM-7S and the biphasic truncated exponential wave by a Laerdal Heartstart 4000. METHODS: Sixty-four patients with clinical indications to undergo external electrical cardioversion were randomized into three groups. All the groups were homogeneous for almost all characteristics, particularly atrial dimensions, body surface area, and duration of AF and therapy. Eighteen patients underwent external cardioversion with monophasic waveform (group 1), 22 patients were treated with rectilinear biphasic waveform (group II), and 24 patients with biphasic truncated waveform (group III). A cardioversion protocol, providing up to 5 shocks, with incremental energy levels was used. A blood sample was obtained 6 hours later to evaluate myocardial damage due to shock therapy for each patient. RESULTS: Both biphasic devices demonstrated to be more effective than the monophasic one (group I 78%, group II 95%, group III 100%). Moreover, none of them caused any significant myocardial damage, evaluated in terms of cardiac enzyme release. Nonetheless, the biphasic truncated exponential wave demonstrated an efficiency of 10 0% compared to 95 % of the rectilinear one and 78% of the monophasic one, using less energy/patient (873 +/- 101 J group I, 390 +/- 48 J group II, and 280 +/- 42 J group III), at almost the same shock attempts. CONCLUSIONS: Biphasic truncated exponential wave seems to be more effective at a lower energy level.

Atrial Fibrillation↗
PubMed2004

[Evaluation of BLS-D training in lay people].

BACKGROUND: The possibility of saving persons with sudden cardiac arrest (SCA) lowers of 10% every minute since the beginning of the event. The early defibrillation (within 4 min) of a person with SCA performed by first responders suitably trained increases the survival rate up to 50%. The basic aim is that early defibrillation is performed as soon as possible by the first responder. METHODS: Within the Public Access Defibrillation (PAD) "Napoli Cuore" Project, 220 highway patrol agents of the Campania Region district were trained through theoretical and practical courses to acquire suitable psychomotor skills to perform the first aid. The learning evaluation was performed with a written exam and a practical test to assess how much every agent had learned about basic life support-defibrillation (BLS-D) schemes. RESULTS: 98.5% of the participants passed the exams and obtained the BLS-D rescuer license, and 15.5% of them obtained the highest score. The analysis of the report cards showed that most of the participants expressed an excellent opinion about this experience. CONCLUSIONS: To implement a PAD project it is necessary to awaken all the structures involved in the campaign against SCA. Hence, it is important that all emergency specialists, public institutions and police departments work all together to make everyone feels safe.

Clinical Competence↗
PubMed2004

Left ventricular pacing in patients with heart failure: evaluation study with Fourier analysis of radionuclide ventriculography.

BACKGROUND: In order to correct the activation, contraction, and relaxation asynchronism, multisite biventricular stimulation has been proposed as a non-pharmacological alternative for the treatment of patients with congestive heart failure (CHF) NYHA class II-III-IV, resistant to maximal drug therapy and with a QRS duration > 120 ms. Fourier analysis appears a feasible technique for the quantitative and non-invasive evaluation of the inter- and intraventricular conduction delays. The aim of our study was to evaluate the usefulness of Fourier analysis when estimating the electromechanical resynchronization in CHF biventricular paced patients and to follow up these patients. METHODS: Forty-five male patients (mean age 64 +/- 5 years) with severe drug-refractory CHF, were submitted to radionuclide ventriculography 14 +/- 7 days, 24 and 36 months after the implantation of a biventricular pacemaker, in order to assess left ventricular ejection fraction using Fourier analysis of the right and left ventricular phase images. Each patient was examined during spontaneous sinus rhythm, P-synchronous right ventricle and P-synchronous biventricular pacing. RESULTS: Fourteen days after biventricular pacemaker implantation, QRS duration decreased from 170 +/- 25 to 147 +/- 25 ms (p < 0.01), left ventricular ejection fraction increased from 24 +/- 6 to 31 +/- 9% (p < 0.005), while standard deviation of the left ventricular phase decreased from 53 +/- 6 to 35 +/- 9 degrees (p < 0.0005). Similar results were obtained at 24 and 36 months. CONCLUSIONS: Biventricular pacing appears to be associated with shortening of QRS duration and an improvement in NYHA class and left ventricular ejection fraction in CHF patients with inter- and intraventricular conduction delays as assessed at Fourier analysis radionuclide ventriculography.

Aged↗
PubMed2003

Involvement of tissue factor pathway inhibitor in the coronary circulation of patients with acute coronary syndromes.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is the endogenous inhibitor of the extrinsic coagulation pathway; however, its involvement during thrombus formation in patients with acute coronary syndromes (ACS) is still unknown. METHODS AND RESULTS: Transcardiac (aorta/coronary sinus) free and total TFPI (free + lipoprotein-bound form) levels, as well as TFPI/factor Xa (FXa) complex levels, were measured in plasma samples obtained from patients with acute myocardial infarction undergoing primary PTCA and patients with unstable angina undergoing urgent PTCA. Patients with stable angina undergoing elective PTCA served as controls. In addition, prothrombin fragment 1+2 and fibrinopeptide A plasma levels were measured. Samples were collected at baseline, after PTCA, and after stent deployment. In patients with ACS, both total and free TFPI plasma levels in the coronary sinus were significantly lower than the corresponding levels measured in the aorta at any time point of the study; conversely, a significant increase in TFPI/FXa complex plasma levels was observed in the coronary sinus as compared with the aorta. In contrast, in patients with stable angina, no differences were observed in TFPI and TFPI/FXa levels at baseline in the coronary sinus as compared with the aorta. CONCLUSIONS: TFPI is involved in the process of thrombus formation in vivo in patients with ACS, which suggests a potential role for TFPI in modulating coronary thrombosis.

Aged↗
PubMed2003

Effect of stent coating alone on in vitro vascular smooth muscle cell proliferation and apoptosis.

Synthetic polymers, like methacrylate (MA) compounds, have been clinically introduced as inert coatings to locally deliver drugs that inhibit restenosis after stent. The aim of the present study was to evaluate the effects of MA coating alone on vascular smooth muscle cell (VSMC) growth in vitro. Stainless steel stents were coated with MA at the following doses: 0.3, 1.5, and 3 ml. Uncoated/bare metal stents were used as controls. VSMCs were cultured in dishes, and a MA-coated stent or an uncoated bare metal stent was gently added to each well. VSMC proliferation was assessed by bromodeoxyuridine (BrdU) incorporation. Apoptosis was analyzed by three distinct approaches: 1) annexin V/propidium iodide fluorescence detection; 2) DNA laddering; and 3) caspase-3 activation and PARP cleavage. MA-coated stents induced a significant decrease of BrdU incorporation compared with uncoated stents at both the low and high concentrations. In VSMCs incubated with MA-coated stents, annexin V/propidium iodide fluorescence detection showed a significant increase in apoptotic cells, which was corroborated by the typical DNA laddering. Apoptosis of VSMCs after incubation with MA-coated stents was characterized by caspase-3 activation and PARP cleavage. The MA-coated stent induced VSMC growth arrest by inducing apoptosis in a dose-dependent manner. Thus MA is not an inert platform for eluting drugs because it is biologically active per se. This effect should be taken in account when evaluating an association of this coating with antiproliferative agents for in-stent restenosis prevention.

Animals↗