EMMA FORTUNATO | International University of Management (original) (raw)

Papers by EMMA FORTUNATO

Research paper thumbnail of A G +1 →A transversion at the 5' splice site of intron 69 of the dystrophin gene causing the absence of peripheral nerve Dp 116 and severe clinical involvement in a DMD patient

Human Molecular Genetics, 1995

Page 1. © 7995 Oxford University Press Human Molecular Genetics, 1995, Vol. 4, No. 11 2171-2174 A... more Page 1. © 7995 Oxford University Press Human Molecular Genetics, 1995, Vol. 4, No. 11 2171-2174 AG+1-^A transversion at the 5' splice site of intron 69 of the dystrophin gene causing the absence of peripheral nerve Dpi 16 and severe clinical involvement in a DMD patient ...

Research paper thumbnail of Prior Exercise Improves Age-Dependent Vascular Endothelial Growth Factor Downregulation and Angiogenesis Responses to Hind-Limb Ischemia in Old Rats

Research paper thumbnail of Exercise promotes angiogenesis and improves -adrenergic receptor signalling in the post-ischaemic failing rat heart

Cardiovascular Research, 2008

Aims We investigated whether exercise training could promote angiogenesis and improve blood perfu... more Aims We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated b-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise. Methods and results Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 + 5%), increased LV end diastolic pressure (20.9 + 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac b-adrenergic receptor downregulation and desensitization. Conclusions Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.

Research paper thumbnail of Exercise promotes angiogenesis and improves b-adrenergic receptor signalling in the post-ischaemic failing rat heart

Aims We investigated whether exercise training could promote angiogenesis and improve blood perfu... more Aims We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated b-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise. Methods and results Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 + 5%), increased LV end diastolic pressure (20.9 + 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac b-adrenergic receptor downregulation and desensitization. Conclusions Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.

Research paper thumbnail of Adverse Cardiovascular Effects of Acute Salt Loading in Young Normotensive Individuals

Research paper thumbnail of Lymphocyte G-protein-coupled receptor kinase-2 is upregulated in patients with Alzheimer's disease

Neuroscience Letters, 2007

Alterations in signal transduction pathway of G-protein-coupled receptors (GPCRs) have been found... more Alterations in signal transduction pathway of G-protein-coupled receptors (GPCRs) have been found in the cerebrocortex and in the peripheral cultured tissues of patients with Alzheimer's disease (AD). The G-protein-coupled receptor kinase-2 (GRK2) plays an important role in regulating the GPCRs signaling: its increased expression is associated with receptor desensitization. The aim of this study was to explore GRK2 levels in peripheral lymphocytes of AD patients and to establish a correlation between lymphocyte protein concentrations and the degree of cognitive impairment. GRK2 mRNA and protein expression were evaluated in the lymphocytes of AD patients with mild or moderate/severe cognitive impairment and in age-matched healthy subjects. Both GRK2 mRNA and protein expression were higher in AD patients lymphocytes compared to controls. Furthermore, lymphocyte GRK2 levels were significantly correlated to the degree of cognitive decline. Our preliminary data suggest that GRK2 is involved in GPCRs coupling dysfunction observed in AD patients. Further studies are needed in order to verify whether the lymphocyte GRK2 might be utilized as a novel biomarker in AD diagnosis and clinical monitoring. Experimental and clinical studies have shown that AD is associated with alterations in GPCRs coupling . In particular, a defective G-protein-enzyme coupling and a decreased GPCRdependent adenylyl cyclase activity are recognized as important mechanisms of GPCRs dysfunction in AD [8]. GRK2, a prototypic member of the GRK family, represents a key molecule in GPCRs regulation . This cytosolic enzyme translocates to the membrane through a specific physical interaction with the membrane-bound ␤␥ subunits of G-proteins inducing a receptor phosphorylation and desensitization. Interestingly, GRK2 is overexpressed in post-mortem hippocampal tissues in AD patients and in rats with chronic brain hypoperfusion . This finding precedes any amyloid deposition representing an *

Research paper thumbnail of Articoli originali

Research paper thumbnail of An intragenic deletion/inversion event in the DMD gene determines a novel exon creation and results in a BMD phenotype

Human Genetics, 2004

Duchenne and Becker Muscular Dystrophy (DMD and BMD) are caused, in the majority of cases, by del... more Duchenne and Becker Muscular Dystrophy (DMD and BMD) are caused, in the majority of cases, by deletions in the dystrophin gene (DMD). Here we describe the unprecedented case of a BMD patient carrying a large out-of-frame intragenic deletion, together with an inversion in the DMD gene, resulting in the inclusion of a novel exon in the transcript. Multiplex PCR amplification revealed the presence of a 48–52 exon deletion, but transcript analysis identified two unexpected products, neither of them including exon 53. The shorter mRNA derived from the juxtaposition of exons 47–54 (in-frame), while the longer one resulted from the inclusion of a novel 73-bp exon between exons 47 and 54. Sequence analysis revealed that the inserted sequence derived from an inverted portion of intron 53; its inclusion is predicted to determine protein truncation. The presence of a genomic inversion involving exon 53 and flanking regions was confirmed, and inversion/deletion breakpoints were sequenced. The inverted 73-bp sequence displays splicing signals at both ends and thus it is probably recognized as a novel exon when the partially inverted hnRNA is processed. These findings highlight the importance of mRNA analysis on patients that, based on routine DNA screenings, do not follow the reading-frame rule. This is the first reported patient carrying both an intragenic deletion and inversion in the DMD locus. This case might provide further insight into both the mechanisms that determine genomic rearrangements in the DMD locus and the molecular signals that drive exon inclusion.

Research paper thumbnail of A G +1 →A transversion at the 5' splice site of intron 69 of the dystrophin gene causing the absence of peripheral nerve Dp 116 and severe clinical involvement in a DMD patient

Human Molecular Genetics, 1995

Page 1. © 7995 Oxford University Press Human Molecular Genetics, 1995, Vol. 4, No. 11 2171-2174 A... more Page 1. © 7995 Oxford University Press Human Molecular Genetics, 1995, Vol. 4, No. 11 2171-2174 AG+1-^A transversion at the 5' splice site of intron 69 of the dystrophin gene causing the absence of peripheral nerve Dpi 16 and severe clinical involvement in a DMD patient ...

Research paper thumbnail of Prior Exercise Improves Age-Dependent Vascular Endothelial Growth Factor Downregulation and Angiogenesis Responses to Hind-Limb Ischemia in Old Rats

Research paper thumbnail of Exercise promotes angiogenesis and improves -adrenergic receptor signalling in the post-ischaemic failing rat heart

Cardiovascular Research, 2008

Aims We investigated whether exercise training could promote angiogenesis and improve blood perfu... more Aims We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated b-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise. Methods and results Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 + 5%), increased LV end diastolic pressure (20.9 + 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac b-adrenergic receptor downregulation and desensitization. Conclusions Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.

Research paper thumbnail of Exercise promotes angiogenesis and improves b-adrenergic receptor signalling in the post-ischaemic failing rat heart

Aims We investigated whether exercise training could promote angiogenesis and improve blood perfu... more Aims We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated b-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise. Methods and results Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 + 5%), increased LV end diastolic pressure (20.9 + 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac b-adrenergic receptor downregulation and desensitization. Conclusions Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.

Research paper thumbnail of Adverse Cardiovascular Effects of Acute Salt Loading in Young Normotensive Individuals

Research paper thumbnail of Lymphocyte G-protein-coupled receptor kinase-2 is upregulated in patients with Alzheimer's disease

Neuroscience Letters, 2007

Alterations in signal transduction pathway of G-protein-coupled receptors (GPCRs) have been found... more Alterations in signal transduction pathway of G-protein-coupled receptors (GPCRs) have been found in the cerebrocortex and in the peripheral cultured tissues of patients with Alzheimer's disease (AD). The G-protein-coupled receptor kinase-2 (GRK2) plays an important role in regulating the GPCRs signaling: its increased expression is associated with receptor desensitization. The aim of this study was to explore GRK2 levels in peripheral lymphocytes of AD patients and to establish a correlation between lymphocyte protein concentrations and the degree of cognitive impairment. GRK2 mRNA and protein expression were evaluated in the lymphocytes of AD patients with mild or moderate/severe cognitive impairment and in age-matched healthy subjects. Both GRK2 mRNA and protein expression were higher in AD patients lymphocytes compared to controls. Furthermore, lymphocyte GRK2 levels were significantly correlated to the degree of cognitive decline. Our preliminary data suggest that GRK2 is involved in GPCRs coupling dysfunction observed in AD patients. Further studies are needed in order to verify whether the lymphocyte GRK2 might be utilized as a novel biomarker in AD diagnosis and clinical monitoring. Experimental and clinical studies have shown that AD is associated with alterations in GPCRs coupling . In particular, a defective G-protein-enzyme coupling and a decreased GPCRdependent adenylyl cyclase activity are recognized as important mechanisms of GPCRs dysfunction in AD [8]. GRK2, a prototypic member of the GRK family, represents a key molecule in GPCRs regulation . This cytosolic enzyme translocates to the membrane through a specific physical interaction with the membrane-bound ␤␥ subunits of G-proteins inducing a receptor phosphorylation and desensitization. Interestingly, GRK2 is overexpressed in post-mortem hippocampal tissues in AD patients and in rats with chronic brain hypoperfusion . This finding precedes any amyloid deposition representing an *

Research paper thumbnail of Articoli originali

Research paper thumbnail of An intragenic deletion/inversion event in the DMD gene determines a novel exon creation and results in a BMD phenotype

Human Genetics, 2004

Duchenne and Becker Muscular Dystrophy (DMD and BMD) are caused, in the majority of cases, by del... more Duchenne and Becker Muscular Dystrophy (DMD and BMD) are caused, in the majority of cases, by deletions in the dystrophin gene (DMD). Here we describe the unprecedented case of a BMD patient carrying a large out-of-frame intragenic deletion, together with an inversion in the DMD gene, resulting in the inclusion of a novel exon in the transcript. Multiplex PCR amplification revealed the presence of a 48–52 exon deletion, but transcript analysis identified two unexpected products, neither of them including exon 53. The shorter mRNA derived from the juxtaposition of exons 47–54 (in-frame), while the longer one resulted from the inclusion of a novel 73-bp exon between exons 47 and 54. Sequence analysis revealed that the inserted sequence derived from an inverted portion of intron 53; its inclusion is predicted to determine protein truncation. The presence of a genomic inversion involving exon 53 and flanking regions was confirmed, and inversion/deletion breakpoints were sequenced. The inverted 73-bp sequence displays splicing signals at both ends and thus it is probably recognized as a novel exon when the partially inverted hnRNA is processed. These findings highlight the importance of mRNA analysis on patients that, based on routine DNA screenings, do not follow the reading-frame rule. This is the first reported patient carrying both an intragenic deletion and inversion in the DMD locus. This case might provide further insight into both the mechanisms that determine genomic rearrangements in the DMD locus and the molecular signals that drive exon inclusion.