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Antoni Bayes-Genis

Publications and source records attributed to Antoni Bayes-Genis.

18 recordsLinked to original sources
PubMed2007

Chimerism and microchimerism of the human heart: evidence for cardiac regeneration.

For decades, it has been widely accepted that the heart is a terminally differentiated organ that is unable to regenerate. Studies of recipients of hearts donated by other humans have shed light on the regenerative potential of the human heart. Investigators have been able to trace the Y chromosome by fluorescence in situ hybridization or polymerase chain reaction, or both, in sex-mismatched heart recipients. Cardiac chimerism has been reported, with concentrations of chimeric cells ranging from 0.04% to 10.0%. Cardiac chimerism after bone marrow or progenitor cell transplantation has also been reported to a low extent (approximately 0.20%), suggesting that a fraction of the extracardiac cells that colonize the myocardium are of bone marrow origin. Cardiac chimerism after pregnancy with male offspring (fetal cell microchimerism) has also been demonstrated. Cells of fetal origin have been shown to be capable of differentiating into myocardial cells. Collectively, we show that chimerism studies provide a proof of concept of a process that it is likely to be part of normal cardiac homeostasis in humans but apparently insufficient for cardiac repair in diseased hearts.

Chimerism↗
PubMed2006

Serial NT-proBNP monitoring and outcomes in outpatients with decompensation of heart failure.

BACKGROUND: NT-proBNP is useful for heart failure (HF) diagnosis and prognosis. We examined the value of serial NT-proBNP monitoring to predict outcomes in decompensated HF patients attending a structured HF clinic. METHODS: Patients with decompensation of established optimally treated HF, not requiring emergency hospital admission, were enrolled in the study. Patients received intensive follow-up weekly during 4 weeks and at 3 months in specialist HF clinics. Serial NT-proBNP concentrations were measured at each visit. Primary endpoint was cardiovascular death and hospital admission for HF at 3 months. RESULTS: Fifty-nine patients were enrolled (60+/-14 years, LVEF 27+/-9%) and 39% had a primary endpoint during follow-up. Baseline NT-proBNP concentration (in ng/L) was 7050+/-6620, and did not differ significantly in patients with and without events (p=0.22). Patients without events showed marked NT-proBNP reduction at week-1 (30% reduction), week-2 (36% reduction), week-3 (34% reduction) and week-4 (37% reduction). By contrast, patients with events showed no significant NT-proBNP reduction during follow-up. Using a general linear model, the relative NT-proBNP reductions (%) at weeks 1-4 were predictors of adverse events (p=0.004, p<0.001, p=0.001 and p=0.03, respectively). In a stepwise multiple Cox regression analysis, NT-proBNP relative reduction (in %) at week 2 was a strong predictor of no events during follow-up (OR 0.79, 95% CI 0.70-0.88, p<0.001). CONCLUSIONS: Serial NT-proBNP monitoring in decompensated HF patients seen in a structured in-hospital HF clinic predicts cardiovascular events during follow-up. NT-proBNP may be useful in an outpatient basis to identify patients at high risk needing more aggressive therapy.

Adrenergic beta-Antagonists↗
PubMed2006

Amino-terminal pro-brain natriuretic Peptide, renal function, and outcomes in acute heart failure: redefining the cardiorenal interaction?

OBJECTIVES: We sought to study the individual and integrative role of amino-terminal pro-brain natriuretic peptide (NT-proBNP) and parameters of renal function for prognosis in heart failure. BACKGROUND: Amino-terminal pro-BNP and renal impairment both predict death in patients with heart failure. Worsening of renal function in heart failure even defines the "cardiorenal syndrome." METHODS: Seven hundred twenty subjects presenting with acute heart failure from 4 university-affiliated medical centers were dichotomized according to NT-proBNP concentration and baseline glomerular filtration rate. In addition, patients were divided according to changes in renal function. The primary end point was 60-day mortality. RESULTS: The combination of a glomerular filtration rate (GFR) <60 ml/min/1.73 m2 with an NT-proBNP >4,647 pg/ml was the best predictor of 60-day mortality (odds ratio 3.46; 95% confidence interval 2.13 to 5.63). Among subjects with an NT-proBNP above the median, those with a GFR <60 ml/min/1.73 m2 or a creatinine rise > or =0.3 mg/dl had the worst prognosis, whereas in subjects with a NT-proBNP below the median, prognosis was not influenced by either impaired renal function at presentation or the development of renal impairment during admission. CONCLUSIONS: The combination of NT-proBNP with measures of renal function better predicts short-term outcome in acute heart failure than either parameter alone. Among heart failure patients, the objective parameter of NT-proBNP seems more useful to delineate the "cardiorenal syndrome" than the previous criteria of a clinical diagnosis of heart failure.

Acute Disease↗
PubMed2006

Adenosine A2A receptors are expressed in human atrial myocytes and modulate spontaneous sarcoplasmic reticulum calcium release.

BACKGROUND: Alterations in the cyclic AMP-dependent regulation of the cardiac ryanodine receptor (RyR2) have been proposed to account for increased spontaneous calcium release from the sarcoplasmic reticulum (SR) in patients with heart failure, ventricular tachyarrhythmias and atrial fibrillation. While the adenosine A(2A) receptor (A(2A)R) is known to regulate cyclic AMP levels, expression and function of this receptor in human cardiac myocytes has not been investigated. METHODS: PCR, western blotting and immunofluorescence were used to identify the A(2A)R, and functional effects of A(2A)R stimulation were measured with confocal calcium imaging and patch-clamp technique. RESULTS: The A(2A)R is expressed in the human right atrium and distributed in a banded pattern along the Z-lines, overlapping with the ryanodine receptor. A(2A)R stimulation caused a protein kinase A dependent increase in spontaneous SR calcium release in isolated human atrial myocytes. The A(2A)R agonist CGS21680 increased the frequency of calcium sparks from 0.12+/-0.03 to 0.31+/-0.08 sparks.mum min(-1) (p<0.05) and calcium waves from 0.65+/-0.31 to 5.11+/-1.84 waves.min(-1) (p<0.03). Moreover, spontaneous Na-Ca exchange currents (I(NCX)) increased from 1.19+/-0.17 to 2.50+/-0.42 min(-1) (p<0.001). In contrast, CGS21680 did not alter caffeine inducible calcium release (6.98+/-0.52 vs. 6.82+/-0.57 amol pF(-1), p=0.6) or the spontaneous I(NCX) amplitude (0.32+/-0.05 vs. 0.29+/-0.04 pA pF(-1), p=0.2). Current-voltage relationship and amplitude of the L-type calcium current (1.62+/-0.18 vs. 1.80+/-0.18 pA pF(-1)) were not altered, but calcium release dependent inactivation was faster with CGS21680 (13.4+/-0.7 vs. 15.8+/-1.0 ms, p<0.001). CONCLUSIONS: Adenosine A(2A) receptors are expressed in the human atrial myocardium and modulate the frequency of spontaneous calcium release from the SR.

Adenosine↗
PubMed2006

Usefulness of intermediate amino-terminal pro-brain natriuretic peptide concentrations for diagnosis and prognosis of acute heart failure.

Age-stratified cutpoints for aminoterminal pro-brain natriuretic peptide (NT-pro-BNP) concentrations are diagnostic in 83% of all subjects with acute dyspnea. This study analyzed subjects with NT-pro-BNP concentrations between the "rule-out" and "rule-in" cutpoints, the so-called natriuretic peptide gray zone. NT-pro-BNP concentrations, clinical characteristics, and 60-day mortality were studied in 1,256 acutely dyspneic patients from an international multicenter study. Of all subjects, 215 had gray-zone NT-pro-BNP concentrations, 116 of whom (54%) were diagnosed with heart failure (HF). Among these subjects, patients with HF were more likely to be older, to have a history of HF, to be in atrial fibrillation, and to have elevated troponin T concentrations compared with those without HF. In multivariate analysis, the use of loop diuretics on presentation (odds ratio [OR] 3.99, 95% confidence interval [CI] 1.58 to 10.1, p = 0.003), paroxysmal nocturnal dyspnea (OR 4.50, 95% CI 1.31 to 15.4, p = 0.02), jugular venous distention (OR 3.05, 95% CI = 1.06 to 8.79, p = 0.04), and the absence of cough (OR 0.18, 95% CI 0.06 to 0.52, p = 0.001) were associated with a diagnosis of acute HF in gray-zone patients. Subjects with HF and diagnostically elevated NT-pro-BNP concentrations had the highest mortality rates, subjects without HF and NT-pro-BNP concentrations < 300 ng/L had the lowest mortality rates, and subjects with gray-zone NT-pro-BNP had intermediate outcomes, irrespective of their final diagnoses. Adding specific clinical information to NT-pro-BNP improves diagnostic accuracy in subjects with intermediate NT-pro-BNP concentrations. Mortality rates in subjects with intermediate NT-pro-BNP concentrations are lower than in those with NT-pro-BNP concentrations diagnostic for HF but are higher than in subjects with NT-pro-BNP concentrations less than the gray zone.

Acute Disease↗
PubMed2006

Effect of aging on the pluripotential capacity of human CD105+ mesenchymal stem cells.

BACKGROUND: Whether aging modifies mesenchymal stem cell (MSC) properties is unknown. AIM: To compare the differentiation capacity of human CD105(+) MSCs obtained from young and elderly donors. METHODS AND RESULTS: Cells were obtained from young (n=10, 24+/-6.4 years) and elderly (n=9, 77+/-8.4 years) donors. Cell senescence was assessed by telomere length assays and lipofuscin accumulation. Cell pluripotentiality was analysed by adipogenic and osteogenic induction media, and myocyte phenotype was attempted with 5-azacytidine (5-AZ). Immunofluorescence, Western blot, transmission electron microscopy and fluo-4 confocal imaging were used to analyse the sarcomere, gap junctions and Ca(2+) dynamics. Cells obtained from young and elderly donors showed no significant differences in relative telomere length (40.1+/-6.4% and 40.3+/-3.6%, p=0.9) and lipofuscin accumulation. Adipogenic and osteogenic potential of CD105(+) MSCs was demonstrated. 5-AZ induced increased expression of sarcomeric proteins without complete sarcomere organization. Treated cells also showed increased presence of connexin-43 both in young and old donor-derived cells. Intercellular communications were verified by the observation of gap junctions and passage of Ca(2+) between neighbouring cells. Spontaneous Ca(2+) raises did not significantly increase after 5-AZ treatment in both age groups. CONCLUSION: Age does not influence the adipogenic and myogenic differentiation potential of human CD105(+) MSCs.

Adult↗
PubMed2005

NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: the International Collaborative of NT-proBNP Study.

AIMS: Experience with amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing for evaluation of dyspnoeic patients with suspected acute heart failure (HF) is limited to single-centre studies. We wished to establish broader standards for NT-proBNP testing in a study involving four sites in three continents. METHODS AND RESULTS: Differences in NT-proBNP levels among 1256 patients with and without acute HF and the relationship between NT-proBNP levels and HF symptoms were examined. Optimal cut-points for diagnosis and prognosis were identified and verified using bootstrapping and multi-variable logistic regression techniques. Seven hundred and twenty subjects (57.3%) had acute HF, whose median NT-proBNP was considerably higher than those without (4639 vs. 108 pg/mL, P<0.001), and levels of NT-proBNP correlated with HF symptom severity (P=0.008). An optimal strategy to identify acute HF was to use age-related cut-points of 450, 900, and 1800 pg/mL for ages <50, 50-75, and >75, which yielded 90% sensitivity and 84% specificity for acute HF. An age-independent cut-point of 300 pg/mL had 98% negative predictive value to exclude acute HF. Among those with acute HF, a presenting NT-proBNP concentration >5180 pg/mL was strongly predictive of death by 76 days [odds ratio=5.2, 95% confidence interval (CI)=2.2-8.1, P<0.001]. CONCLUSION: In this multi-centre, international study, NT-proBNP testing was valuable for diagnostic evaluation and short-term prognosis estimation in dyspnoeic subjects with suspected or confirmed acute HF and should establish broader standards for use of the NT-proBNP in dyspnoeic patients.

Acute Disease↗
PubMed2005

Identification of male cardiomyocytes of extracardiac origin in the hearts of women with male progeny: male fetal cell microchimerism of the heart.

BACKGROUND: Fetal progenitor cells may cross the placenta during pregnancy, persist for decades in the maternal bloodstream, and find a microenvironment conducive to colonization in a variety of maternal solid organs. Whether extracardiac fetal progenitors are present in the heart of women with male issue is unknown. METHODS: The hearts from 2 non-pregnant women who had given birth to 2 and 3 male children, respectively, were studied. Myocardial specimens from 2 men and 2 women (without history of pregnancies) were used as controls. Real time polymerase chain reaction was performed to amplify the SRY gene located at the Y chromosome. Fluorescence in situ hybridization (FISH) with probes specific for X and Y chromosomes was combined with alpha-actin immunohistochemistry to identify cardiac muscle cells. Histocompatibility studies were conducted in both patients and their male relatives. RESULTS: The SRY gene was amplified in the myocardium of both patients. FISH analysis showed clear evidence of male cells with the typical cardiomyocyte phenotype within the myocardium. X- and Y-chromosome bodies in the nuclei were found in 0.25% and 0.20% of cells, respectively. Increased human leukocyte antigen compatibility was observed between patients and their sons. CONCLUSIONS: This study identified male cardiomyocytes of extracardiac origin, presumably fetal, in the hearts of 2 women with male progeny. Fetal progenitor cells may colonize the heart and under appropriate microenvironmental stimuli, differentiate into cardiomyocytes.

Cardiomyopathy, Dilated↗
PubMed2005

Transient biventricular dysfunction following pericardiocentesis.

We report the case of a 41-year-old woman admitted to the hospital due to cardiac tamponade as the first manifestation of a pulmonary neoplasm. The patient developed an early biventricular dysfunction and pulmonary edema after removal of the pericardial effusion, with complete recovery within ten days. Since transient ventricular dysfunction after pericardiocentesis is a very unusual complication, we present a review of the different mechanisms suggested in the literature to explain the pathophysiology of this rare phenomenon.

Adult↗
PubMed2005

Pretreatment with corticosteroids attenuates the efficacy of colchicine in preventing recurrent pericarditis: a multi-centre all-case analysis.

AIMS: Effective prevention of recurrent pericarditis remains an important yet elusive goal. Corticosteroid therapy often needs to be continued for a prolonged period and causes severe side effects. We performed a multi-centre all-case analysis to investigate the efficacy of colchicine in preventing subsequent relapses of pericarditis, and addressed the hypothesis that pretreatment with corticosteroids may attenuate the beneficial effect of colchicine. METHODS AND RESULTS: One hundred and forty published and unpublished cases of patients treated with colchicine after at least two relapses of pericarditis were aggregated from European centres. Of those, 119 were included in the study group. Only 18% of the patients had relapses under colchicine therapy, and 30% after its discontinuation. There were significantly more relapses among male patients after colchicine treatment (36 vs. 17%, P=0.046), and those with previous corticosteroid treatment (43 vs. 13%, P=0.02). Multivariate logistic regression analysis identified previous corticosteroid therapy (OR 6.68, 95% CI: 1.65-27.02) and male gender (OR 4.20, 95% CI: 1.16-15.21) as independent risk factors for recurrence following colchicine therapy. CONCLUSION: Treatment with colchicine is highly effective in preventing recurrent pericarditis, while pretreatment with corticosteroids exacerbates and extends the course of recurrent pericarditis.

Adolescent↗
PubMed2004

N-terminal pro-brain natriuretic peptide reflects pulmonary capillary leakage in patients with acute dyspnea.

Natriuretic peptides have proved useful in the diagnosis of heart failure in patients presenting to the emergency department with shortness of breath. Dyspnea and orthopnea in heart failure are clinical expressions of pulmonary capillary congestion and leakage, which may be assessed by the percentage of pulmonary hemosiderin-laden macrophages (HLM) in induced sputum. We found a significant difference in the percentage of HLM present in sputum among patients with acute heart failure, patients with noncardiac dyspnea with ventricular dysfunction, and patients without heart failure (p = 0.008). N-terminal pro-brain natriuretic peptide (N-BNP) concentrations were also different among these 3 patient groups (p = 0.006). N-BNP concentrations were positively associated with the percentage of HLM in patients with acute dyspnea (r = 0.6; p < 0.0001). N-BNP, in addition to being a ventricular dysfunction marker, may reflect the severity of pulmonary capillary congestion and leakage in patients with acute shortness of breath.

Acute Disease↗
PubMed2004

Cardiac chimerism in recipients of peripheral-blood and bone marrow stem cells.

Multipotent progenitor cells have the ability to differentiate into most somatic cell types, including cardiac myocytes. We sought to investigate cardiac chimerism after peripheral-blood and bone marrow stem cell transplantation. Between 10 and 17 highly polymorphic short tandem repeat (STR) markers were assayed in DNA obtained from donors' peripheral blood, recipients' peripheral blood before transplantation, and the recipient's heart in every patient. Gender and non-gender STR donor alleles were identified in the recipient heart in three patients. Using a highly sensitive PCR assay to determine donor and recipient genotypes, we confirmed the existence of cardiac chimerism in recipients of peripheral-blood and bone marrow stem cells.

Adult↗
PubMed2003

New insights into elastin and vascular disease.

Elastin is synthesized and secreted by vascular smooth muscle cells and is the major extracellular matrix component deposited in the arterial wall. When last reviewed by this journal in 1994, the link between elastin and a rare occlusive vascular disease had just been established. Since that time, it has become increasingly clear that elastin is a critical autocrine factor that maintains vascular homeostasis through a combination of biomechanical support and biologic signaling. This review examines the complexity of elastin-smooth muscle cell interactions, and how new insights may impact understanding of the pathogenesis and treatment of vascular disease.

Animals↗
PubMed2003

Effects of insulin-like growth factor-I on cultured human coronary artery smooth muscle cells.

The growth-promoting effects of insulin-like growth factor-I (IGF-I) appear to be different in vascular smooth muscle cells from various segments of the arterial tree. Little information exists on human coronary artery smooth muscle cells (CoSMC), the primary elements of coronary atherosclerosis and post-angioplasty restenosis. In this study we determined the effects of IGF-I on cultured human CoSMC. Type I IGF receptors (IGF-R) were present on CoSMC as assessed by affinity cross-linking of 125I-IGF-I to monolayer cultures. IGF-I was a weak mitogen, 1.5-fold increase in [3H]thymidine incorporation, for CoSMC. However, IGF-I had a potent motility effect on CoSMC with a 314+/-12% increase in cell migration (P<0.001), comparable to that of 5% FBS. IGF-I-stimulated motility was partially inhibited by alphaIR-3, a specific IGF-R inhibitor (P<0.05). Addition of kistrin, a disintegrin, or LM609, a specific alpha(V)beta(3) integrin neutralizing antibody, abolished IGF-I-stimulated migration (P<0.001). This study indicates that IGF-I is a potent motility agent for human CoSMC via the alpha(V)beta(3) integrin receptor, but exerts little mitogenic effect. Because CoSMC migration plays a crucial role in atherosclerosis and restenosis, IGF-I blockade has the potential to limit lumen reduction.

Cell Movement↗
PubMed2003

Distinct left bundle branch block pattern in ischemic and non-ischemic dilated cardiomyopathy.

BACKGROUND: A high percentage of patients with dilated cardiomyopathy have the electrocardiographic (ECG) pattern of advanced left bundle branch block (LBBB). In the present study we sought to investigate whether patients with dilated cardiomyopathy of ischemic or non-ischemic etiology can be differentiated on the basis of LBBB pattern. METHODS AND RESULTS: The study population included 41 patients with dilated cardiomyopathy of non-ischemic (NIC) (n=26) or ischemic origin (IC) (n=15) and LBBB on surface ECG. ECG duration and voltage were digitally measured. The presence of notching of S wave in right precordial leads (V1-V3) was not statistically different between the groups. The voltages of precordial leads V2, V3 and the Sigma(V1+V2+V3 voltages) were significantly more prominent in patients with NIC (P=0.002, P<0.001 and P=0.002, respectively). The discriminative power of receiver operating characteristic analysis was best at voltages of V3 of 2100 microV (area under the curve, 0.805; standard error, 0.001). The sensitivity and specificity of V3 voltage >2100 microV on surface ECG in the presence of LBBB to identify a cardiomyopathy of non-ischemic origin were 85 and 73%, respectively. CONCLUSIONS: A single ECG criteria, voltage of lead V3, appears to be a useful parameter to identify patients with dilated cardiomyopathy of ischemic or non-ischemic origin in the presence of advanced LBBB.

Adult↗
PubMed2002

Host cell-derived cardiomyocytes in sex-mismatch cardiac allografts.

BACKGROUND: Mesenchymal precursor cells are able to respond to tissue signals and differentiate into a phenotype characteristic of mature cells of that tissue. We sought to investigate whether adult human cardiomyocytes can be derived from recipient precursor cells in sex-mismatched cardiac allografts. METHODS: We studied four male patients who received hearts from female donors, and four female patients who received an allograft from a male donor. Four sex-matched transplant patients, two of each sex served as controls. Combined fluorescence in situ hybridization with probes specific for X- and Y-chromosomes and immunohistochemistry with alpha-actin was used to identify cardiac muscle cells 4 and 12 months after transplantation. Slides were examined with a fluorescence microscope to detect the presence of male cells with one X and one Y signal in the nucleus, and female cells containing two X signals. RESULTS: Mature cardiomyocytes from the host (1-2%) were found in five endomyocardial biopsy specimens at 4 months, and in three specimens at 12 months. In addition, recipient cells negative for cytoplasmic alpha-actin were also identified (1-21% per slide). The number of infiltrating recipient cells was not associated with the degree of rejection of the sample or with the number of prior rejection episodes. Echocardiographic evaluation showed no improvement in cardiac performance in hearts from patients with more than 10% chimeric recipient cells. CONCLUSIONS: Our data confirm the existence of mature cardiomyocytes derived from host cells, likely mesenchymal precursors, in the adult cardiac allograft in vivo.

Actins↗
PubMed2002

Macrophages, myofibroblasts and neointimal hyperplasia after coronary artery injury and repair.

Macrophages participate in the restenosis process through the release of cytokines, metalloproteinases and growth factors. Studies of peritoneal granulation tissue suggest that macrophages may be precursors of myofibroblasts. This study examined the contribution of monocyte/macrophage lineage cells to neointimal cellular mass in a porcine model of thermal vascular injury. Thermal coronary artery injury caused medial smooth muscle cell necrosis and transformation of the media into an extracellular matrix barrier. The neointimal hyperplasia that developed over the injury sites was evaluated by light microscopy, electron microscopy and immunohistochemistry. At day 3, blood monocytes were adhered to the vessel wall and infiltrated the fibrotic media. At day 14, 42+/-3.9% of neointimal cells had a monocytic nuclear morphology and expressed macrophage-specific antigen SWC3 (identified by monoclonal antibody DH59B). Moreover, 9.2+/-1.8% of neointimal cells co-expressed SWC3 and alpha-smooth muscle actin and had ultrastructural characteristics intermediate between macrophages and myofibroblasts. At day 28, 10.5+/-3.5% of cells expressed SWC3 and 5.2+/-1.8% of cells co-expressed SWC3 and alpha-smooth muscle actin. This study indicates that hematopoietic cells of monocyte/macrophage lineage abundantly populate the neointima in the process of lesion formation and may be precursors of neointimal myofibroblasts after thermal vascular injury.

Analysis of Variance↗