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Francesco Romeo

Publications and source records attributed to Francesco Romeo.

At least 37 records · Page 2Linked to original sources
PubMed2004

Regulatory role of endothelium in the expression of genes affecting arterial calcification.

Vascular calcification is a highly regulated process sharing features of bone mineralization. Since endothelium regulates many of the processes during atherogenesis, we monitored the expression of genes involved in calcification upon exposure of human coronary artery endothelial cells (HCAECs) to atherogenic stimuli. Genes studied were: core binding factor alpha-1 (Cbfa1/Runx2), a pivotal transcriptional regulator of osteogenesis; bone morphogenetic protein-2 (BMP2), an inducer of cartilage and bone; and matrix gla-protein (MGP), a potent inhibitor of calcification, which exerts its action by blocking BMP2. HCAECs were treated with oxidized-low density lipoprotein (ox-LDL, 80 microg/mL) or tumor necrosis factor-alpha (TNFalpha, 10 ng/mL), and the expression of Cbfa1, BMP2, and MGP was quantified by real-time PCR. Cbfa1 was expressed at low levels in untreated HCAECs, and its expression did not change with ox-LDL or TNFalpha treatment. The expression of BMP2 and MGP increased early after exposure to ox-LDL or TNFalpha (at 2-8 h), and the increase was not evident at 24 h. Ox-LDL exerted a stronger effect on MGP than on BMP2 expression. The effects of ox-LDL, but not TNFalpha, on MGP and BMP2 expression were inhibited by pretreatment of cells with an antibody directed at LOX-1, a lectin-like receptor for ox-LDL (10 microg/mL). Thus, the endothelium, when exposed to atherogenic stimuli, ox-LDL in particular, regulates the process of calcification by enhancing the expression of the bone inhibitory MGP, while the expression of Cbfa1 remains unchanged. Upregulation of BMP2 may represent a feedback upregulation in response to increase in MGP. The effect of ox-LDL appears to be mediated by LOX-1 activation.

Antibodies↗
PubMed2004

The protective effect of superoxide dismutase mimetic M40401 on balloon injury-related neointima formation: role of the lectin-like oxidized low-density lipoprotein receptor-1.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the principal receptor for oxidized low-density lipoprotein (ox-LDL) in vascular endothelial cells (ECs), has recently been suggested to exert a pivotal role in atherogenesis, possibly by mediating ox-LDL-evoked endothelial dysfunction. On the other hand, LOX-1 expression seems to strongly correlate with the oxidative stress occurring in the vascular wall of experimentally injured blood vessels. Here, we investigated LOX-1 expression and superoxide generation during neointima formation in a balloon injury rat carotid artery model. To test this, we used M40401 [a manganese(II) complex with a bis(cyclo-hexylpyridine-substituted) macrocyclic ligand], a synthetic superoxide dismutase mimetic that is a selective scavenger of superoxide. The injury was performed inserting the balloon catheter through the rat common carotid artery and after 14 days a histopathological analysis revealed a significant restenosis with smooth muscle cell proliferation and neointima formation that was associated with an enhanced expression of LOX-1, nitrotyrosine (the footprint of peroxynitrite) staining, and lipid peroxidation as assessed by malondialdehyde (MDA) formation. Pretreatment of rats with M40401 (0.5-10 mg/kg i.p. daily) reduced neointima formation, MDA accumulation, nitrotyrosine staining, and LOX-1 expression. Here, we show that removal of superoxide formation occurring in injured arteries reduces both neointima formation and LOX-1 expression and that this may represent a novel therapeutical approach in the treatment of vascular disorders in which proliferation of vascular smooth muscle cells and ox-LDL-related endothelial cell dysfunction occur.

Animals↗
PubMed2004

Accuracy of thin-slice computed tomography in the detection of coronary stenoses.

AIM: Our aim was to investigate the accuracy of multislice spiral computed tomography (MSCT) in the detection of significant (>50%) coronary stenosis using a scanner equipped for 16 x 0.625 mm collimation. METHODS: In 64 patients (59 male, mean age 58 +/- 5 years) with suspected coronary artery disease, MSCT (GE Light Speed-16, collimation: 16 x 0.625 mm) was performed 20 +/- 5 days before coronary angiography (CAG). Only angiographic segments >1.5 mm were considered for analysis. RESULTS: In all patients, MSCT was carried out without complications. Three patients were excluded from the analysis. Of 729 angiographic segments, 613 (84%) were judged evaluable by MSCT. Considering only the segments judged evaluable, the sensitivity was 89%, specificity 98%, positive predictive value 90%, and negative predictive value 98%. Including all segments in the analysis (evaluable and nonevaluable), sensitivity was 78%. CONCLUSIONS: Using a scanner with a collimation of 16 x 0.625 mm, our study confirms the potential role of MSCT in the detection of significant coronary stenosis with a sensitivity of 89% and a very high specificity (98%). Exclusion criteria and less than full evaluability of the coronary arteries must still be considered limitations of the method.

Coronary Stenosis↗
PubMed2004

The slippery slope.

Explore the source record for details and available documents.

Blood Flow Velocity↗
PubMed2004

Limitations of four-slice multirow detector computed tomography in the detection of coronary stenosis.

BACKGROUND: Our aim was to compare 4-slice spiral computed tomography with conventional coronary angiography in the detection of significant (> 50%) coronary stenosis. METHODS: Sixty-two patients (41 males, 21 females, mean age 60 +/- 8 years) with suspected coronary artery disease were submitted to coronary angiography and then to multislice spiral computed tomography (GE Light Speed 4 slice) performed 12 +/- 5 days later. RESULTS: We excluded 25% of the patients from analysis because of a heart rate > 70 b/min or because of frequent ectopic beats. We also excluded from analysis 23% of all the angiographic segments judged not evaluable at multislice spiral computed tomography. Within these limits, the sensitivity was 65%, the specificity 98%, the positive predictive value 88%, and the negative predictive value 92%. CONCLUSIONS: By considering the intrinsic limitations such as its low temporal and spatial resolution, 4-slice spiral computed tomography has a limited applicability and has to be used with caution in the evaluation of native coronary arteries.

Aged↗
PubMed2003

Usefulness of coronary flow reserve measured by transthoracic coronary Doppler ultrasound to detect severe left anterior descending coronary artery stenosis.

Transthoracic coronary Doppler ultrasound during venous adenosine infusion showed damped (<1) coronary flow velocity reserve in patients with severe left anterior descending coronary artery stenosis. Damped coronary flow reserve discriminated severe from nonsevere stenosis with high sensitivity, specificity, and positive predictive accuracy, and is a unique noninvasive tool to identify high-risk patients.

Adenosine↗
PubMed2003

Expression of lectin-like oxidized low-density lipoprotein receptors during ischemia-reperfusion and its role in determination of apoptosis and left ventricular dysfunction.

OBJECTIVES: The goal of this study was to determine the role of lectin-like oxidized low-density lipoprotein receptors (LOX-1), a recently identified oxidized low-density lipoprotein (ox-LDL) receptor, in ischemia-reperfusion injury to the heart. BACKGROUND: Reactive oxygen species (ROS) released during ischemia-reperfusion oxidize low-density lipoproteins; LOX-1 is upregulated by ox-LDL and ROS, and is involved in cell injury. METHODS: Anesthetized rats were subjected to left coronary artery ligation for 60 min (n = 10, ischemia group), or ischemia followed by 60 min of reperfusion (n = 30, ischemia-reperfusion group). Rats in the latter group were treated with saline, the LOX-1 blocking antibody JXT21 (10 mg/kg), or nonspecific anti-goat immunoglobulin G (IgG) (10 mg/kg). Ten other rats underwent thoracotomy without coronary ligation (sham control). RESULTS: Ischemia-reperfusion was associated with an increase in LOX-1 expression, lipid peroxidation and apoptosis, a large infarct area, and a decrease in left ventricular function (all, p < 0.01 vs. sham control and ischemia alone groups). Treatment of rats with LOX-1 antibody prevented ischemia-reperfusion-induced upregulation of LOX-1. Importantly, the LOX-1 antibody reduced apoptosis by 48%, lipid peroxidation by 39%, and myocardial infarct size by 45%, and improved left ventricular function (first derivative of pressure measured over time: -47% to -18%, p < 0.01). Nonspecific IgG had no effect. CONCLUSIONS: Lectin-like oxidized low-density lipoprotein receptors are upregulated during myocardial ischemia-reperfusion, and appear to be associated with apoptosis, necrosis, and left ventricular functional deterioration.

Animals↗
PubMed2003

Noninvasive coronary flow reserve assessed by transthoracic coronary Doppler ultrasound in patients with left anterior descending coronary artery stents.

Noninvasive measurement of coronary flow reserve (CFR) (hyperemic/flow velocity ratio at rest) by transthoracic Doppler echocardiography showed normalization of flow in the left anterior descending (LAD) coronary artery early after stenting. We hypothesized that noninvasive CFR may reveal in-stent restenosis at follow-up. Therefore, we studied 134 patients, 0 to 72 months after successful proximal-middle LAD stenting, and 38 controls. LAD flow velocity was measured by transthoracic Doppler echocardiography during 90 seconds venous adenosine infusion (140 microg/kg/min). CFR was measured in diastole. According to angiography, patients who received stents were divided into 3 groups: group I, <50% LAD in-stent restenosis (n = 83); group II, nonsignificant (50% to 69%) LAD in-stent restenosis (n = 17); and group III, significant (> or = 70%) LAD in-stent restenosis (n = 34). LAD CFR was similar in group I and controls (2.90 +/- 0.58 vs 3.05 +/- 0.81; p = NS), it was slightly lower in group II (2.42 +/- 0.33) compared with controls and group I (p <0.001 vs both), and clearly abnormal (<2) in group III (1.38 +/- 0.48) compared with controls, and groups I and II (p <0.001). A CFR <2 had 91% sensitivity, 95% specificity, and 96% positive and 97% negative predictive values to detect significant stenosis in patients with LAD stents. Our data show that noninvasive Doppler assessment of CFR allows identification of significant LAD in-stent restenosis, based on a cut-off value of <2.

Adenosine↗
PubMed2003

A clinical variant of familial Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive inherited disease consisting of (1) partial oculocutaneous albinism (with nystagmus, strabism, and visual acuity loss), (2) platelet storage pool deficiency (with bleeding diathesis), and (3) disorder of "ceroid" metabolism with a multisystem tissue lysosomal ceroid deposition. HPS is less uncommon in Puerto Rico, where the most important studies have been performed, but is a very rare disease in Europe. HPS basic defect remains unknown, even if an HPS-causing gene was identified in chromosome segment 10q23-q23.3, and several mutations have been reported. The aim of this article is to discuss, on the basis of a review of relevant literature, a new familial HPS clinical variant observed in 2 young sisters (aged 16 and 23 years old, respectively), characterized by the typical symptoms of this syndrome. Our patients also suffered from diffuse interstitial pulmonary disease and an unexpectedly increased platelet aggregation and were prone to bacterial infections. Interestingly, we observed urinary tract abnormality in the younger HPS sister and a porencephalic cyst in the older HPS sister; both of these developmental defects have been reported in the Cross syndrome (or oculocerebral hypopigmentation syndrome). It seems that in our patients, an overlapping of the phenotypic manifestations of different rare syndromes may be present. The presence of ceroid-like autofluorescent material in urinary sediment together with the histologic aspects and the autofluorescence of oral mucosa biopsy are consistent with a ceroid-like lipofuscin storage. HPS should be carefully tested for in suspected cases to prevent the severe visual impairment, rapidly progressive pulmonary fibrosis, and other complications associated with this disorder.

Adolescent↗
PubMed2003

Role of genetics in prevention of coronary atherosclerosis.

Atherosclerosis is currently regarded as a complex disorder, triggered by gene-gene and gene-environment interactions. Despite the difficulties of multifactorial disease genetic analysis, significant progress has been achieved in the search for atherosclerosis susceptibility genes. Here, we review these advances with regard to genome scan results and candidate gene analysis.

Coronary Artery Disease↗
PubMed2003

Value of echocardiography in predicting future cardiac events after acute myocardial infarction.

Short- and long-term survival after acute myocardial infarction mainly depends on three factors: the amount of myocardium that had become necrotic, the area of myocardium at further risk of becoming necrotic, and the patency of the infarct-related artery. Echocardiography is a low-cost, safe, bedside, repeatable tool, particularly useful for prognostic stratification after myocardial injury. Two-dimensional echocardiography analyzes left ventricular function, the most powerful predictor of survival immediately after acute myocardial infarction. Myocardial contrast echocardiography measures the infarct size and detects viable myocardium. Stress echocardiography stratifies patients with viable myocardium and/or multivessel coronary artery disease who need further diagnostic and therapeutic interventions. Transthoracic coronary Doppler ultrasonography assesses effective recanalization and coronary flow reserve of the left anterior descending coronary artery. Further technologic advances are needed to allow direct noninvasive measurement of flow by transthoracic Doppler ultrasonography in other coronary arteries.

Acute Disease↗
PubMed2002

Immunosuppressive Therapy for the Prevention of Restenosis after Coronary Artery Stent Implantation (IMPRESS Study).

OBJECTIVES: This study tested the effect of oral prednisone on clinical and angiographic restenosis rate after successful stent implantation in patients with persistent elevation of systemic markers of inflammation after the procedure. BACKGROUND: Experimental studies have shown that corticosteroids have the potential to reduce the inflammatory response associated with stent implantation. METHODS: Eighty-three patients undergoing successful stenting with C-reactive protein (CRP) levels >0.5 mg/dl 72 h after the procedure were randomized to receive oral prednisone or placebo for 45 days. The primary clinical end point was 12-month event-free survival rate (defined as freedom from death, from myocardial infarction, and from recurrence of symptoms requiring additional revascularization). The angiographic end points were restenosis rate and late loss at six months. RESULTS: Twelve-month event-free survival rates were 93% and 65% in patients treated with prednisone and placebo, respectively (relative risk [RR] 0.18, 95% confidence intervals [CI], 0.05 to 0.61, p = 0.0063). Six-month restenosis rate and late loss were lower in prednisone-treated than in placebo-treated patients (7% vs. 33%, p = 0.001, and 0.39 +/- 0.6 mm vs. 0.85 +/- 0.6 mm, p = 0.001, respectively). CONCLUSIONS: In patients with persistently high CRP levels after successful coronary artery stent implantation, oral immunosuppressive therapy with prednisone results in a striking reduction of clinical events and angiographic restenosis rate.

Adult↗
PubMed2002

Measurement of coronary flow reserve in the anterior and posterior descending coronary arteries by transthoracic Doppler ultrasound.

We describe for the first time transthoracic Doppler ultrasound assessment of coronary flow reserve (CFR) in both the posterior descending (PDA) and left anterior descending (LAD) coronary arteries. CFR (hyperemic/resting diastolic flow velocity ratio) was measured by 90-second intravenous adenosine infusion (140 microg/kg/min). Baseline PDA flow was detected in 62 of 81 subjects (76%), and the CFR was measurable in 44 of them (54%) because of adenosine-induced hyperventilation. According to angiography, these 44 subjects were divided into 3 groups: group 1 (0% to 29% stenosis), group 2 (30% to 69% stenosis), and group 3 (> or =70% stenosis). PDA CFR was 2.62 +/- 0.25 in 17 patients in group 1, 2.33 +/- 0.32 in 9 patients in group 2, and 1.40 +/- 0.54 in 18 patients in group 3 (F = 41.83, p <0.0001). LAD CFR was 3.31 +/- 0.54 in 15 patients in group 1, 2.49 +/- 0.71 in 10 patients in group 2, and 1.12 +/- 0.49 in 19 patients in group 3 (F = 65.68, p <0.0001). A cut-off of <2 identified > or =70% stenosis in both of the arteries supplying the PDA and in the LAD. Noninvasive measurement of PDA CFR is feasible and may improve with technologic advancement and the use of selective adenosine receptor agonists, thus preventing hyperventilation.

Aged↗
PubMed2002

Coronary recanalization in anterior myocardial infarction: the open perforator hypothesis.

OBJECTIVE: Patent perforators, noninvasively imaged by transthoracic color-Doppler echocardiography, may reflect adequate reperfusion in anterior myocardial infarction (MI). BACKGROUND: The Thrombolysis In Myocardial Infarction (TIMI) classification may not fully reflect adequate myocardial reperfusion in MI. METHODS: We studied 61 patients with anterior MI undergoing thrombolysis (n = 28), primary stenting (n = 20), or neither one (n = 13). High-resolution color-Doppler ultrasound was used to image the left anterior descending coronary artery (LAD) and perforators in four segments of the anterior-apical wall and to build a new recanalization score (RS). The TIMI flow was assessed by angiography. Wall motion score index (WMSI), ejection fraction (EF), end-diastolic volume index, and end-systolic volume index (ESVI) were measured by echocardiography at baseline and at three-month follow-up. Linear regression equations, considering RS or TIMI flow as independent variables, were compared among these functional recovery parameters. A multivariate linear model, predicting percent changes of WMSI, EF, or ESVI, was used to investigate the contribution of several clinical covariates along with RS and TIMI flow. RESULTS: Sensitivity, specificity, and diagnostic accuracy of color-Doppler ultrasound in detecting LAD patency were 86%, 98%, and 97%, respectively. Mean and peak flow velocities discriminated (0.004 < p < 0.008) TIMI flow but not RS. Regression equations showed that RS discriminated better than TIMI flow recovery of ventricular function (p < 0.012). The RS was the best single multivariate predictor (p < 0.0001) of percent changes in WMSI, EF, and ESVI. CONCLUSIONS: Transthoracic color-Doppler ultrasound detects an open LAD after MI. Perforators reflect adequate myocardial reperfusion and are early noninvasive markers of myocardial viability.

Aged↗
PubMed2002

Mixed tocopherol preparation is superior to alpha-tocopherol alone against hypoxia-reoxygenation injury.

Hypoxia-reoxygenation (H-R) is associated with alterations in oxidant-antioxidant balance and L-arginine-nitric oxide system. Tocopherols decrease the activity of reactive oxygen species (ROS) and yet are not beneficial in clinical trials. It has been proposed that mixed tocopherols as found in nature may be more tissue protective than alpha-tocopherol alone found in commercial preparations. We compared the effect of a mixed tocopherol preparation with that of alpha-tocopherol alone on superoxide dismutase (SOD) activity and iNOS expression in cultured myocytes exposed to H-R. Myocytes from Sprague-Dawley rat hearts were subjected to hypoxia for 24 h followed by reoxygenation for 3 h H-R. Parallel groups of myocytes were pretreated with alpha-tocopherol alone or a mixed-tocopherol preparation (containing alpha-, gamma-, and delta-tocopherols) (50 microM) for 30 min. H-R resulted in myocyte injury (determined by LDH release), a decrease in SOD activity and an upregulation of iNOS expression/activity. Both tocopherol preparations attenuated cell injury and markedly decreased the effects of H-R on SOD activity and iNOS expression/activity (all P < 0.05 vs H-R group, n = 5). However, mixed-tocopherol preparation was much superior to alpha-tocopherol in terms of myocyte protection from the adverse effect of H-R (P < 0.05). Lack of efficacy of commercial tocopherol preparations in clinical trials may reflect absence of gamma- and delta-tocopherols.

Animals↗
PubMed2002

Dexamethasone inhibits the inducible bioconversion of glyceryl trinitrate to nitric oxide.

The aim of this study was to assess the effects of dexamethasone (DEX) on the inducible bioconversion of glyceryl trinitrate (GTN) into nitric oxide in cultured smooth muscle cells, endothelial cells, and the J774 macrophage cell line as well as in vivo and ex vivo in rats either untreated or pretreated with Escherichia coli lipopolysaccharide. In vitro, an increased bioconversion of GTN to nitrite and an elevation of cyclosine guanosine 3,5;-monophosphate (cGMP) levels occurred after treatment with lipopolysaccharide (LPS) (0.5 microg/ml, 18 h). This effect was ablated by co-incubation with DEX (10 microM, 18 h). Rats treated with an intraperitoneal (IP) injection of LPS (4 mg/kg) 18 h beforehand showed enhanced hypotensive responses to GTN (1 mg/kg, intravenously [IV]) and this was prevented when DEX (4 mg/kg, IP) was given together with LPS. Progesterone (50 mg/kg, IP) had no effect on GTN-induced hypotensive response. Conversely, exposure of rat aortic strips obtained from animals pretreated with LPS produced an enhanced vasorelaxant response in LPS-treated rats. Also, this effect was inhibited by pretreatment with DEX. Thus, the induction of the pathway leading to the formation of nitric oxide from GTN is blocked by DEX both in vitro and in vivo, and this may represent a useful tool in the assessment of the enhanced bioconversion of organic nitrates into nitric oxide occurring via inflammatory mechanisms.

Animals↗