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Biomedical subjects

P R Moreno

Publications and source records attributed to P R Moreno.

At least 19 recordsLinked to original sources
PubMed2006

Intraplaque hemorrhage.

Intraplaque hemorrhage is a common feature of atherosclerotic plaques and is considered one of the identifying features of complex lesions preceding acute ischemic events. The cause of intraplaque hemorrhage is most often secondary to rupture of neovessels, which have invaded the plaque. However, inflammation and metabolic factors such as diabetes may also precipitate hemorrhage from mature microvessels by damaging the endothelium. The mechanism by which hemorrhage destabilizes the plaque is in large part secondary to the action of hemoglobin released from red blood cells at the site of the hemorrhage. Hemoglobin is a potent pro-inflammatory agent by virtue of its ability to promote formation of ROS. The major defense mechanism against the toxic effects of extracorpuscular hemoglobin is the protein haptoglobin, which tightly binds to hemoglobin and prevents it from catalyzing oxidative reactions. There exists a common allelic polymorphism in the haptoglobin gene, which has recently been strongly associated with the risk of cardiovascular disease in multiple independent cohorts. The protein products of the two different haptoglobin alleles differ in their ability to serve as an antioxidant against hemoglobin and also to activate the CD163 receptor. This review presents a unifying hypothesis whereby the haptoglobin genotype is proposed to modulate the response to intraplaque hemorrhage and thereby play a fundamental role in determining the morphological and metabolic features of complex plaques preceding acute ischemic events.

Animals↗
PubMed2006

Neovascularization in human atherosclerosis.

In the absence of disease, microvessels provide vessel wall nutrients to the tunica media, while the intima is fed by oxygen diffusion from the lumen. As disease evolves and the tunica intima thickens, oxygen diffusion is impaired, and microvessels become the major source for nutrients to the vessel wall. Microvessels serve as a port of entry for inflammatory cells, from the systemic circulation to the nascent atherosclerotic lesion. As disease progress, microvessels also play a role in intraplaque hemorrhage, lipid core expansion, and plaque rupture. In addition, microvessels are also involved in stent restenosis, and plaque regression. Therefore, microvessels are a pivotal component of atherosclerosis, and proper patient risk-stratification in the near future may include the detection of increased neovascularization in atherosclerotic lesions. This review divided in two parts summarizes the current understanding of atherosclerosis neovascularization, starting with the normal anatomy and physiology and progressing to more advanced stages of the disease. We will review the structure and function of vasa vasorum in health and disease, the mechanisms responsible for the angiogenic process, the role of the immune system, including inflammation and Toll-like receptors, and the pathology of microvessels in early atherosclerotic plaques. Furthermore, the review addresses the advanced stages of atherosclerosis, summarizing the progressive role for microvessels during disease progression, red blood cell extravasation, lipid core expansion, plaque rupture, healing, repair, restenosis, and disease regression, offering the clinician a state-of-the-art, "bench to bedside" approach to neovascularization in human atherosclerosis.

Animals↗
PubMed2006

Atherosclerosis neovascularization and imaging.

Neovascularization in atherosclerotic plaques is particularly prominent in complicated lesions, and has been recently identified as a marker of plaque vulnerability. This observation has led to a growing interest in the development of imaging techniques with the ability to visualize and quantify the extent of plaque neovascularization. Such feature may play an important role in identifying those lesions more prone to destabilization and rupture, and in the guidance and monitoring of therapeutic interventions. Several modalities have emerged as potential candidates for imaging neovessels in atherosclerotic lesions. They include magnetic resonance imaging, x-ray computed tomography, positron emission tomography, single photon emission computed tomography, ultrasound, or near-infrared optical imaging. These techniques differ in their achievable spatial and temporal resolution, availability, cost, reproducibility, degree of intrusiveness, capability to image atherosclerotic plaques in various vascular territories and ability to discern different plaque components, specifically the presence of neovessels. Molecular imaging, a rapidly evolving multidisciplinary field devoted to the visualization of specific physiopathologic processes at the cellular or molecular level, appears particularly well suited for this purpose because of its ability to target and visualize individual molecules specific to neoangiogenesis. In this manuscript we will review current evidence on the potential application of the various modalities, with a particular emphasis in molecular imaging.

Animals↗
PubMed2006

Metabolic syndrome and diabetic atherothrombosis: implications in vascular complications.

Metabolic syndrome is characterized by the clustering of a number of metabolic abnormalities in the presence of underlying insulin resistance with a strong association with diabetes and cardiovascular disease morbidity and mortality. The disorder is defined in different ways, but the pathophysiology is attributable to insulin resistance. An increased release of free fatty acids (FFAs) from adipocytes block insulin signal transduction pathway, induce endothelial dysfunction due to increased reactive oxygen species (ROS) generation and oxidative stress. Dyslipidemia, associated with high levels of triglycerides and low concentrations of high density lipoproteins (HDLs), contributes to a proinflammatory state. Inflammation, the key pathogenic component of atherosclerosis, promotes thrombosis, a process that underlies acute coronary event and stroke. Tissue factor, a potent trigger of the coagulation cascade, is increased in diabetes with poor glycemic control. Therapeutic lifestyle changes (weight loss and physical activity) along with pharmacological interventions are recommended to prevent the complications of metabolic syndrome. In addition to statins, metformin, blood pressure lowering medications, interventions to increase HDLs are other important approaches to decrease the risk of cardiovascular disease. Furthermore, the peroxisome proliferator activated receptor (PPAR)-alpha and gamma agonists are potent anti-inflammatory and anti-atherogenic agents that could both improve insulin sensitivity and the long-term cardiovascular risk. In this review we focus on the molecular and pathophysiological basis of metabolic syndrome, which augments diabetes (insulin resistance) and the contribution of neovascularization in the plaque progression in diabetes, leading to rupture and coronary thrombosis.

Animals↗
PubMed2001

A computer-assisted approach for chemotaxonomic studies--diterpenes in Lamiaceae.

This paper describes a new computer approach for chemotaxonomic studies. The methodology employed enables the search for chemical substructures as taxonomic descriptors using an expert system built with plant natural products. The operation of the system was tested with diterpenes as taxonomic markers in Lamiaceae.

Databases, Factual↗
PubMed2000

Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus.

BACKGROUND: Lipid-rich, inflamed atherosclerotic lesions are associated with plaque rupture and thrombosis, which are the most important causes of death in patients with diabetes mellitus. This study was designed to quantify lipid composition and macrophage infiltration in the coronary lesions of patients with diabetes mellitus. METHODS AND RESULTS: A total of 47 coronary atherectomy specimens from patients with diabetes mellitus were examined and compared with 48 atherectomy specimens from patients without diabetes. Plaque composition was characterized by trichrome staining. Macrophage infiltration was characterized by immunostaining. Clinical and demographic data were similar in both groups. The percentage of total area occupied by lipid-rich atheroma was larger in specimens from patients with diabetes (7+/-2%) than in specimens from patients without diabetes (2+/-1%; P:=0.01), and the percentage of total area occupied by macrophages was larger in specimens from patients with diabetes (22+/-3%) than in specimens from patients without diabetes (12+/-1%; P:=0.003). The incidence of thrombus was also higher in specimens from patients with diabetes than in specimens from patients without diabetes (62% versus 40%; P:=0.04). Plaque composition, macrophage infiltration, and thrombus were similar in lesions from diabetic patients treated with insulin compared with lesions from patients treated with sulfonylureas or diet. CONCLUSIONS: Coronary tissue from patients with diabetes exhibits a larger content of lipid-rich atheroma, macrophage infiltration, and subsequent thrombosis than tissue from patients without diabetes. These differences suggest an increased vulnerability for coronary thrombosis in patients with diabetes mellitus.

Aged↗
PubMed1999

Histopathologic comparison of human coronary in-stent and post-balloon angioplasty restenotic tissue.

Histomorphometric studies for smooth muscle cells, macrophages, tissue factor, collagen, and cell proliferation were performed on 20 atherectomy specimens from patients with in-stent restenosis and 20 specimens from patients with post-balloon PTCA restenosis. Smooth muscle cell content was larger and proliferation index was higher in in-stent restenotic tissue; macrophage, tissue factor, and collagen content were larger in post-balloon percutaneous transluminal coronary angioplasty restenotic tissue, suggesting a more cellular and proliferative response with less thrombogenic potential in human tissue from in-stent restenosis than tissue from post-balloon percutaneous transluminal coronary angioplasty restenosis.

Aged↗
PubMed1999

Echocardiography can predict the development of severe mitral regurgitation after percutaneous mitral valvuloplasty by the Inoue technique.

Severe mitral regurgitation (MR) following mitral balloon valvuloplasty is a major complication of this procedure. We recently described a new echocardiographic score that can predict the development of severe MR following mitral valvuloplasty with the double balloon technique. The present study was designed to test the usefulness of this score for predicting severe MR in patients undergoing the procedure using the Inoue balloon technique. From 117 consecutive patients who underwent mitral valvuloplasty using the Inoue technique, 14 (11.9%) developed severe MR after the procedure. A good quality echocardiogram before mitral valvuloplasty was available in 11 patients. These 11 patients were matched by age, sex, mitral valve area, and degree of MR before valvuloplasty with 69 randomly selected patients who did not develop severe MR after Inoue valvuloplasty. The total MR-echocardiographic (MR-echo) score was significantly greater in the severe MR group (10.5 +/- 1.4 vs 8.2 +/- 1.1; p <0.001). In addition, the component grades for the anterior leaflet (2.9 +/- 0.5 vs 2.2 +/- 0.4; p <0.001), posterior leaflet (2.6 +/- 0.7 vs 1.9 +/- 0.8), commissures (2.4 +/- 0.8 vs 2.0 +/- 0.5; p <0.05) and subvalvular apparatus (2.6 +/- 0.5 vs 1.9 +/- 0.4; p <0.001) were also higher in the MR group. Using a total score of > or = 10 as a cut-off point for predicting severe MR with the Inoue technique, a sensitivity of 82%, specificity of 91%, accuracy of 90%, and negative predictive value of 97% were obtained. Stepwise logistic regression analysis identified the MR-echo score as the only independent predictor for developing severe MR with the Inoue technique (p <0.0001). Thus, the MR-echo score can also predict the development of severe MR following mitral balloon valvuloplasty using the Inoue technique.

Catheterization↗
PubMed1999

Mitral balloon valvotomy for patients with mitral stenosis in atrial fibrillation: immediate and long-term results.

OBJECTIVES: The purpose of this study was to examine the effect of atrial fibrillation (AF) on the immediate and long-term outcome of patients undergoing percutaneous mitral balloon valvuloplasty (PMV). BACKGROUND: There is controversy as to whether the presence of AF has a direct negative effect on the outcome after PMV. METHODS: The immediate procedural and the long-term clinical outcome after PMV of 355 patients with AF were prospectively collected and compared with those of 379 patients in normal sinus rhythm (NSR). RESULTS: Patients with AF were older (62 +/- 12 vs. 48 +/- 14 years; p < 0.0001) and presented more frequently with New York Heart Association (NYHA) class IV (18.3% vs. 7.9%; p < 0.0001), echocardiographic score >8 (40.1% vs. 25.1%; p < 0.0001), calcified valves under fluoroscopy (32.4% vs. 18.8%, p < 0.0001) and with history of previous surgical commissurotomy (21.7% vs. 16.4%; p = 0.0002). In patients with AF, PMV resulted in inferior immediate and long-term outcomes, as reflected in a smaller post-PMV mitral valve area (1.7 +/- 0.7 vs. 2 +/- 0.7 cm2; p < 0.0001) and a lower event free survival (freedom of death, redo-PMV and mitral valve surgery) at a mean follow-up time of 60 months (32% vs. 61%; p < 0.0001). In the group of patients in AF, severe post-PMV mitral regurgitation (> or =3+) (p = 0.0001), echocardiographic score >8 (p = 0.004) and pre-PMV NYHA class IV (p = 0.046) were identified as independent predictors of combined events at follow-up. CONCLUSIONS: Patients with AF have a worse immediate and long-term outcomes after PMV. However, the presence of AF by itself does not unfavorably influence the outcome, but is a marker for clinical and morphologic features associated with inferior results after PMV.

Adult↗
PubMed1999

Tissue characteristics of restenosis after percutaneous transluminal coronary angioplasty in diabetic patients.

OBJECTIVES: The purposes of this study were to analyze coronary specimens from patients with diabetes mellitus (DM) and to compare them with specimens from patients without DM. BACKGROUND: Diabetes mellitus is associated with an increased incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Increased hypercellular smooth muscle cell proliferation with exaggerated intimal hyperplasia formation may be responsible for this predisposition. METHODS: Eighteen coronary atherectomy specimens with restenosis after PTCA from patients with DM were compared with 18 coronary atherectomy specimens with restenosis after PTCA from patients without DM. Total and segmental areas were quantified on trichrome-stained tissue of hypercellular tissue, collagen-rich sclerotic tissue, atheroma and thrombus. Demographic and angiographic data were similar in both groups. RESULTS: The percentage of total plaque area composed of hypercellular tissue was lower in restenotic specimens from patients with DM than in restenotic specimens from patients without DM (19 +/- 6% vs. 44 +/- 5%; p = 0.003). The percentage of collagen-rich sclerotic tissue area was larger in restenotic specimens from patients with DM than in restenotic specimens from patients without DM (77 +/- 9% vs. 53 +/- 4%; p = 0.004). The percentages of atheroma and thrombus were similar in both groups. CONCLUSIONS: Intimal hypercellular tissue content is reduced in restenotic tissue from patients with DM. Collagen-rich sclerotic content is increased in restenotic lesions from patients with DM. These results suggest an accelerated fibrotic rather than a proliferative response in diabetic lesions from patients with restenosis after PTCA.

Aged↗
PubMed1999

Purification and cDNA cloning of isochorismate synthase from elicited cell cultures of Catharanthus roseus.

Isochorismate is an important metabolite formed at the end of the shikimate pathway, which is involved in the synthesis of both primary and secondary metabolites. It is synthesized from chorismate in a reaction catalyzed by the enzyme isochorismate synthase (ICS; EC 5.4.99.6). We have purified ICS to homogeneity from elicited Catharanthus roseus cell cultures. Two isoforms with an apparent molecular mass of 64 kD were purified and characterized. The Km values for chorismate were 558 and 319 microM for isoforms I and II, respectively. The isoforms were not inhibited by aromatic amino acids and required Mg2+ for enzyme activity. Polymerase chain reaction on a cDNA library from elicited C. roseus cells with a degenerated primer based on the sequence of an internal peptide from isoform II resulted in an amplification product that was used to screen the cDNA library. This led to the first isolation, to our knowledge, of a plant ICS cDNA. The cDNA encodes a protein of 64 kD with an N-terminal chloroplast-targeting signal. The deduced amino acid sequence shares homology with bacterial ICS and also with anthranilate synthases from plants. Southern analysis indicates the existence of only one ICS gene in C. roseus.

Amino Acid Sequence↗
PubMed1998

Histopathology of coronary lesions with early loss of minimal luminal diameter after successful percutaneous transluminal coronary angioplasty: is thrombus a significant contributor?

BACKGROUND: Early loss of minimal luminal diameter of >0.3 mm after successful percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher incidence of restenosis. The underlying mechanism of this early loss is unknown and thrombus may be a contributing factor. METHODS: We performed a prospective study using quantitative computerized planimetry on coronary tissue specimens obtained by directional coronary atherectomy of 24 lesions in which early loss occurred 22+/-9 minutes after successful PTCA. RESULTS: Thrombus was present in 9 (37%) of 24 coronary specimens. Segmental areas (mm2) and percentage of total area were distributed as follows: sclerotic tissue, 4.07+/-0.7 mm2 (63%+/-6%); fibrocellular tissue, 0.97+/-0.27 mm2 (16%+/-4%); hypercellular tissue, 0.99+/-0.29 mm2 (12%+/-3%); atheromatous gruel, 0.18+/-0.07 mm2 (3%+/-0.1%); and thrombus, 0.24+/-0.15 mm2 (6%+/-0.4%). There was no difference in the relative early loss index between lesions with or without thrombus (35%+/-7% vs 26%+/-2%, respectively; P= .87). Multiple stepwise regression analysis did not identify any histologic predictors of relative early loss index. CONCLUSION: Histopathologic analysis of coronary lesions with early loss after successful PTCA suggests that thrombus may not play a significant role in this angiographic phenomenon.

Adult↗
PubMed1996

Macrophages, smooth muscle cells, and tissue factor in unstable angina. Implications for cell-mediated thrombogenicity in acute coronary syndromes.

BACKGROUND: Macrophage expression of tissue factor may be responsible for coronary thrombogenicity in patients with plaque rupture. In patients without plaque rupture, smooth muscle cells may be the thrombogenic substrate. This study was designed to identify the cellular correlations of tissue factor in patients with unstable angina. METHODS AND RESULTS: Tissue from 50 coronary specimens (1560 pieces) from patients with unstable angina and 15 specimens from patients with stable angina were analyzed. Total and segmental areas (in square millimeters) were identified with trichrome staining. Macrophages, smooth muscle cells, and tissue factor were identified by immunostaining. Tissue factor content was larger in unstable angina (42 +/- 3%) than in stable angina (18 +/- 4%) (P = .0001). Macrophage content was also larger in unstable angina (16 +/- 2%) than in stable angina (5 +/- 2%) (P = .002). The percentage of tissue factor located in cellular areas was larger in coronary samples from patients with unstable angina (67 +/- 8%) than in samples from patients with stable angina (40 +/- 5%) (P = .00007). Multiple linear stepwise regression analysis showed that coronary tissue factor content correlated significantly (r = .83, P < .0001) with macrophage and smooth muscle cell areas only in tissue from patients with unstable angina, with a strong relationship between tissue factor content and macrophages in the atheromatous gruel (r = .98, P < .0001). CONCLUSIONS: Tissue factor content is increased in unstable angina and correlates with areas of macrophages and smooth muscle cells, suggesting a cell-mediated thrombogenicity in patients with acute coronary syndromes.

Adult↗
PubMed1996

Macrophage infiltration predicts restenosis after coronary intervention in patients with unstable angina.

BACKGROUND: Restenosis remains the major limitation of percutaneous coronary revascularization. Macrophages release cytokines, metalloproteinases, and growth factors that may induce smooth muscle cell migration and proliferation. We tested the hypothesis that primary lesions that develop restenosis after coronary atherectomy have more macrophages and smooth muscle cells than primary lesions that do not develop restenosis. METHODS AND RESULTS: Fifty patients with unstable angina were identified. Total and segmental areas were quantified on trichrome-stained sections of coronary atherectomy tissue. Macrophages and smooth muscle cells were identified by immunohistochemical staining. Restenosis, defined as > 50% stenosis diameter by quantitative cineangiography, was present in 30 patients. The other 20 patients (< 50% stenosis) constitute the "no restenosis" group. The percentages of smooth muscle cell areas were similar in specimens from patients with and without restenosis (57 +/- 5% and 52 +/- 6%) (P = NS). However, macrophage-rich areas were larger in plaque tissue from patients with restenosis (20.4 +/- 2%) than in tissue from patients without restenosis (9.3 +/- 2%) (P = .0007). Multiple stepwise logistic regression analysis identified macrophages as the only independent predictor for restenosis (P = .006). CONCLUSIONS: Macrophages are increased in coronary atherectomy tissue from primary lesions that develop restenosis, suggesting a possible role for macrophages in the restenotic process after percutaneous coronary intervention.

Adult↗
PubMed1996

Comparison of the usefulness of Doppler pressure half-time in mitral stenosis in patients < 65 and > or = 65 years of age.

Doppler pressure half-time is a reliable method for estimating mitral valve area when net left atrial and ventricular compliance remain stable. The accuracy of Doppler pressure half-time in estimating mitral valve area in older patients is unknown. We studied 80 patients (65 women and 15 men, aged 56 +/- 14 years) with cardiac catheterization and echocardiography. Mitral valve area was calculated using the Gorlin formula and by the Doppler pressure half-time method. Patients were stratified into those aged < 65 years (n = 57), and those aged > or = 65 years (n = 23). The discordance between pressure half-time and Gorlin-derived mitral valve area was assessed and related to multiple clinical, echocardiographic, and hemodynamic variables. The difference between pressure half-time and Gorlin-derived mitral valve area was greater in the older than in the younger patient (0.34 +/- 0.30 vs 0.15 +/- 0.27 cm2, p = 0.009) but the older group had smaller mitral valve areas by the Gorlin method (0.72 +/- 0.18 vs 0.89 +/- 0.32 cm2, p = 0.02) and lower cardiac output. The difference between pressure half-time and Gorlin remained greater in the group of older patients (0.32 +/- 0.30 vs 0.19 +/- 0.22 cm2, p = 0.04), even when the analysis was restricted to patients with similar mitral valve area (< 1 cm2 by the Gorlin method). Using multivariate analysis, age > or = 65 years remained the only significant predictor of the discrepancy between pressure half-time and Gorlin mitral valve area. Thus, when compared with Gorlin-derived mitral valve area, pressure half-time overestimated valve area in older patients, and this technique for estimating mitral valve area should be used with caution in patients > or = 65 years of age.

Age Factors↗
PubMed1996

Inhaled nitric oxide increases coronary artery patency after thrombolysis.

BACKGROUND: Nitric oxide (NO) and nitrosovasodilators that release NO inhibit platelet aggregation. The antithrombotic effect of intravenously infused nitrosovasodilators is usually accompanied by systemic vasodilation. Inhaled NO is a pulmonary vasodilator that does not produce systemic hemodynamic effects. This study examines the antithrombotic effect of inhaled NO in a canine model of platelet-mediated coronary artery reocclusion after thrombolysis. METHODS AND RESULTS: In 25 anesthetized dogs, a segment of the left anterior descending coronary artery was traumatized and a high-grade stenosis created. Thrombus was injected at this site, and tissue plasminogen activator was administered, producing cyclic flow variations (CFVs) in 24 of 25 dogs. CFV frequency was unchanged in dogs not breathing NO but decreased by 35 +/- 9% (P < .05) and 53 +/- 7% (P < .01) while dogs breathed 20 and 80 parts per million (ppm) NO, respectively. The coronary artery patency ratio (fraction of time during which the coronary artery was patent; CAPR) was unchanged in dogs not treated with NO but increased from 51 +/- 7% to 64 +/- 8% while breathing 20 ppm NO (P < .01) and from 49 +/- 3% to 75 +/- 7% while breathing 80 ppm NO (P < .01). The increased CAPR during 80 ppm NO administration persisted during a 45-minute posttreatment period (70 +/- 7%, P < .05 versus baseline). NO inhalation did not change systemic hemodynamics. In a pharmacological model of coronary vasoconstriction, inhaled NO did not reverse the effect of the thromboxane A2 agonist U-46619. In vitro ADP-induced platelet aggregation was inhibited by NO gas. CONCLUSIONS: Inhaled NO at concentrations of 20 and 80 ppm increases coronary patency and decreases CFV frequency in a canine model of platelet-mediated coronary reocclusion after thrombolysis without producing systemic hemodynamic effects.

Adenosine Diphosphate↗
PubMed1996

Ervatamia coronaria: chemical constituents and some pharmacological activities.

A new bisindole alkaloid, 19,20-dihydroervahanine A was isolated from the stems of Ervatamia coronaria grown in Brazil, together with five known alkaloids: coronaridine, heyneanine, voacristine, voacamine, descarbomethoxyvoacamine and five phenolic acids: vanillic, gentisic, syringic, 4-hydroxybenzoic and salicylic acid. The aqueous and alcoholic extracts, when administered p.o. or i.p. to rats 1 h before subplantar injection of carrageenin had a significant anti-inflammatory effect. The alcoholic extract also had an analgesic effect and increased the pentobarbital induced sleeping time.

Alkaloids↗