Biomedical subjects

Valentin Fuster

Publications and source records attributed to Valentin Fuster.

At least 19 recordsLinked to original sources

PubMed2007

Gene therapy and stem cell therapy for cardiovascular diseases today: a model for translational research.

Clinical trials looking at ways to promote myocardial regeneration have reported that the administered therapies have either neutral effects or modest benefits of questionable impact. These somewhat disappointing results should emphasize the need for translational research, with bidirectional feedback between the basic research laboratory and the clinical arena. Such a translational pathway is illustrated by the quest to find an effective therapy for restenosis, which culminated in the development of sirolimus. At this point a move away from the bedside and a return to the bench seems necessary to better understand the mechanisms of action of progenitor cells and stimulating factors. Without such basic knowledge research might be prematurely discouraged and the opportunity to fully understand the true potential of cardiovascular regenerative therapy might be missed.

Cardiovascular Diseases↗

PubMed2007

Myocardial cell therapy at the crossroads.

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Animals↗

PubMed2006

Haptoglobin genotype is a determinant of iron, lipid peroxidation, and macrophage accumulation in the atherosclerotic plaque.

OBJECTIVE: Intraplaque hemorrhage increases the risk of plaque rupture and thrombosis. The release of hemoglobin (Hb) from extravasated erythrocytes at the site of hemorrhage leads to iron deposition, which may increase oxidation and inflammation in the atherosclerotic plaque. The haptoglobin (Hp) protein is critical for protection against Hb-induced injury. Two common alleles exist at the Hp locus and the Hp 2 allele has been associated with increased risk of myocardial infarction. We have demonstrated decreased anti-oxidative and anti-inflammatory activity for the Hp 2 protein. We tested the hypothesis that the Hp 2-2 genotype is associated with increased oxidative and macrophage accumulation in atherosclerotic plaques. METHODS AND RESULTS: The murine Hp gene is a type 1 Hp allele. We created a murine type 2 Hp allele and targeted its insertion to the Hp locus by homologous recombination. Atherosclerotic plaques from C57Bl/6 ApoE-/- Hp 2-2 mice were associated with increased iron (P=0.008), lipid peroxidation (4-hydroxynonenal and ceroid) and macrophage accumulation (P=0.03) as compared with plaques from C57Bl/6 ApoE-/- Hp 1-1 mice. CONCLUSIONS: Increased iron, lipid peroxidation and macrophage accumulation in ApoE-/- Hp 2-2 plaques suggests that the Hp genotype plays a critical role in the oxidative and inflammatory response to intraplaque hemorrhage.

Alleles↗

PubMed2006

In vivo coronary plaque histology in patients with stable and acute coronary syndromes: relationships with hyperlipidemic status and statin treatment.

OBJECTIVES: Aim of the study was to investigate whether maintained moderate statin treatment influence atheroma, macrophage content, neoangiogenesis and/or haemorrhage in coronary plaques from patients with non-fatal coronary syndromes. METHODS: A total of 48 patients underwent elective directional coronary atherectomy on "de novo" culprit lesions; 16 patients had non-treated hypercholesterolemia, 16 patients received maintained moderate statin treatment for hypercholesterolemia and 16 had no lipoprotein abnormalities. These three patients groups were matched for age and clinical diagnosis of stable angina (SA) or unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI). Atherectomy specimens were stained with antibodies against macrophages, endothelial cells and glycophorin A. Results of histology and immunohistochemistry were morphometrically analyzed by using computer-assisted image analysis. RESULTS: Atheroma and fibrous tissue, neoangiogenesis, macrophage and haemorrhage (i.e., glycophorin A) differed between the three groups (P<0.05). Statin-treated group showed significantly decreased atheroma (P=0.016), fibrous tissue (P=0.42), macrophage content (P=0.012), neoangiogenesis (P=0.00048) and haemorrhage (P=0.0092) as compared with the non-treated hyperlipidemic group. CONCLUSIONS: The present findings show that maintained moderate statin treatment may contribute to plaque stabilization in non-fatal coronary syndromes by decreasing intraplaque neoangiogenesis and haemorrhage, lipid burden and macrophage content, and, on the other hand, by increasing plaque collagenization.

Acute Disease↗

PubMed2006

ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation).

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Algorithms↗

PubMed2006

ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.

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Algorithms↗

PubMed2006

ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing Committee to Revise the 1998 guidelines for the management of patients with valvular heart disease) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons.

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Heart Valve Diseases↗

PubMed2006

ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons.

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Adolescent↗

PubMed2006

ACC/AHA 2006 guideline update on perioperative cardiovascular evaluation for noncardiac surgery: focused update on perioperative beta-blocker therapy: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society for Vascular Medicine and Biology.

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Adrenergic beta-Antagonists↗

PubMed2006

ACC/AHA 2006 guideline update on perioperative cardiovascular evaluation for noncardiac surgery: focused update on perioperative beta-blocker therapy: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society for Vascular Medicine and Biology.

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Humans↗

PubMed2006

Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation.

BACKGROUND: Coronary atherosclerosis and its thrombotic complications are the major cause of mortality and morbidity throughout the industrialized world. Thrombosis on disrupted atherosclerotic plaques plays a key role in the onset of acute coronary syndromes. Macrophages density is one of the most critical compositions of plaque in both plaque vulnerability and thrombogenicity upon rupture. It has been shown that macrophages have a high uptake of 18F-FDG (FDG). We studied the correlation of FDG uptake with histopathological macrophage accumulation in atherosclerotic plaques in a rabbit model. METHODS: Atherosclerosis was induced in rabbits (n = 6) by a combination of atherogenic diet and balloon denudation of the aorta. PET imaging was performed at baseline and 2 months after atherogenic diet and coregistered with magnetic resonance (MR) imaging. Normal (n = 3) rabbits served as controls. FDG uptake by the thoracic aorta was expressed as concentration (muCi/ml) and the ratio of aortic uptake-to-blood radioactivity. FDG uptake and RAM-11 antibody positive areas were analyzed in descending aorta. RESULTS: Atherosclerotic aortas showed significantly higher uptake of FDG than normal aortas. The correlation of aortic FDG uptake with macrophage areas assessed by histopathology was statistically significant although it was not high (r = 0.48, p < 0.0001). When uptake was expressed as the ratio of aortic uptake-to-blood activity, it correlated better (r = 0.80, p < 0.0001) with the macrophage areas, due to the correction for residual blood FDG activity. CONCLUSION: PET FDG activity correlated with macrophage content within aortic atherosclerosis. This imaging approach might serve as a useful non-invasive imaging technique and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion.

Journal Article↗

PubMed2006

Detection of healed myocardial infarction with multidetector-row computed tomography and comparison with cardiac magnetic resonance delayed hyperenhancement.

Decreased myocardial attenuation on contrast-enhanced multidetector computed tomography (MDCT) images can be observed in subjects with myocardial infarctions (MIs). It was hypothesized that myocardial hypoattenuation in MDCT can accurately detect the presence of a healed MI as determined by cardiac magnetic resonance delayed hyperenhancement (CMR-DH). Coronary MDCT and CMR-DH were performed in 42 subjects. Pre- and postcontrast MDCT images were analyzed for the presence of myocardial hypoattenuation, and volumes of MIs were quantified on MDCT and CMR-DH images in a blinded manner. The sensitivity, specificity, and negative and positive predictive values of postcontrast MDCT for the detection of MI were 91%, 81%, 83%, and 90%, respectively. MI sizes by postcontrast MDCT and by CMR-DH were strongly correlated (r=0.87, p<0.0001), although MDCT systematically underestimated MI volume (2.7+/-2.5 vs 25.9+/-19.9 ml, p<0.0001). MI size by MDCT was correlated negatively with the left ventricular ejection fraction (r=-0.62, p=0.03) and positively with left ventricular volumes (r=0.68 to 0.72, p<0.01). In 71% of subjects with MIs by CMR-DH, corresponding areas of hypoattenuation were noted also in precontrast MDCT. In conclusion, healed MIs can be detected as areas of myocardial hypoattenuation on MDCT images with high diagnostic accuracy, although their sizes are largely underestimated compared with CMR-DH. The presence of precontrast hypoattenuation suggests that mechanisms independent of reduced contrast delivery contribute to this finding.

Adolescent↗

PubMed2006

Neovascularization in human atherosclerosis.

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Angiotensin II↗

PubMed2006

Fenofibrate induces plaque regression in hypercholesterolemic atherosclerotic rabbits: in vivo demonstration by high-resolution MRI.

INTRODUCTION: Fenofibrate has shown to reduce major cardiovascular events and slow angiographic progression of coronary atherosclerosis. The postulated mechanism of action is via the activation of peroxisomal proliferator-activated receptor-alpha (PPAR-alpha), a nuclear transcription factor that controls a variety of cellular functions. We investigated the anti-atherogenic effects of fenofibrate on previously established experimental atherosclerotic lesions. METHOD: Atherosclerotic lesions were induced in the abdominal aorta of New Zealand white (NZW) rabbits (n=19) by a combination of a double-balloon injury and a 9-month hypercholesterolemic diet. The rabbits were randomized into placebo or fenofibrate group. The corresponding treatments were added to the hypercholesterolemic diet. All rabbits underwent MRI examination at randomization and after 6 months of treatment, and were then sacrificed for histopathology. RESULTS: LDL-cholesterol was similarly elevated at randomization and follow-up, and was not significantly modified by fenofibrate therapy. HDL-cholesterol decreased (-27+/-10%, p=0.04) in the placebo and increased (+36.8+/-2%, p=0.04) in the fenofibrate group. MRI showed comparable vessel wall area (VWA) at randomization in both groups. At 15months, a significant increase in VWA was seen in the placebo group (15+/-4%, p=0.007), while fenofibrate treatment was associated with a regression (-11+/-4%, p=0.041) of previously established lesions. Fenofibrate also decreased macrophage and increased smooth muscle cell/collagen content of atherosclerotic lesions. CONCLUSION: MRI measurements can, in conjunction with in vitro histological measurements, contribute to the understanding of the actions of pharmacologic agents in experimental models of atherosclerosis. Fenofibrate significantly regresses atherosclerotic lesions and induced changes in plaque composition associated with a more "stable" phenotype (reduced macrophages and increased SMC). These observations support the potential anti-atherogenic effects of PPAR-alpha agonists.

Animals↗

PubMed2006