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3. Role of HLA matching and donor specific antibody development in long-term survival, acute rejection and cardiac allograft vasculopathy

Author

Costa, Dario, Picascia, Antonietta, Grimaldi, Vincenzo, Amarelli, Cristiano, Petraio, Andrea, Levi, Anna, Di Donato, Mario, Pirozzi, Anna Virginia Adriana, Fiorito, Carmela, Moccia, Giusi, Gallo, Aurora, Strozziero, Mariagrazia, Marra, Claudio, De Feo, Marisa, Cacciatore, Francesco, Maiello, Ciro, and Napoli, Claudio

Published
2024
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6. Sodium/glucose cotransporter 2 (SGLT2) inhibitors improve cardiac function by reducing JunD expression in human diabetic hearts

Author

Marfella, Raffaele, D'Onofrio, Nunzia, Trotta, Maria Consiglia, Sardu, Celestino, Scisciola, Lucia, Amarelli, Cristiano, Balestrieri, Maria Luisa, Grimaldi, Vincenzo, Mansueto, Gelsomina, Esposito, Salvatore, D'Amico, Michele, Golino, Paolo, Signoriello, Giuseppe, De Feo, Marisa, Maiello, Ciro, Napoli, Claudio, and Paolisso, Giuseppe

Published
2022
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7. Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts

Author

Marfella, Raffaele, D’Onofrio, Nunzia, Mansueto, Gelsomina, Grimaldi, Vincenzo, Trotta, Maria Consiglia, Sardu, Celestino, Sasso, Ferdinando Carlo, Scisciola, Lucia, Amarelli, Cristiano, Esposito, Salvatore, D’Amico, Michele, Golino, Paolo, De Feo, Marisa, Signoriello, Giuseppe, Paolisso, Pasquale, Gallinoro, Emanuele, Vanderheyden, Marc, Maiello, Ciro, Balestrieri, Maria Luisa, Barbato, Emanuele, Napoli, Claudio, and Paolisso, Giuseppe

Published
2022
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11. Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte

Author

D’Onofrio, Nunzia, Scisciola, Lucia, Sardu, Celestino, Trotta, Maria Consiglia, De Feo, Marisa, Maiello, Ciro, Mascolo, Pasquale, De Micco, Francesco, Turriziani, Fabrizio, Municinò, Emilia, Monetti, Pasquale, Lombardi, Antonio, Napolitano, Maria Gaetana, Marino, Federica Zito, Ronchi, Andrea, Grimaldi, Vincenzo, Hermenean, Anca, Rizzo, Maria Rosaria, Barbieri, Michelangela, Franco, Renato, Campobasso, Carlo Pietro, Napoli, Claudio, Municinò, Maurizio, Paolisso, Giuseppe, Balestrieri, Maria Luisa, and Marfella, Raffaele

Published
2021
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26. Detrimental Effects of Bartonella henselae Are Counteracted by L-Arginine and Nitric Oxide in Human Endothelial Progenitor Cells

Author

Salvatore, Paola, Casamassimi, Amelia, Sommese, Linda, Fiorito, Carmela, Ciccodicola, Alfredo, Rossiello, Raffaele, Avallone, Bice, Grimaldi, Vincenzo, Costa, Valerio, Rienzo, Monica, Colicchio, Roberta, Williams-Ignarro, Sharon, Pagliarulo, Caterina, Prudente, Maria Evelina, Abbondanza, Ciro, Lamberti, Florentia, Baroni, Adone, Buommino, Elisabetta, Farzati, Bartolomeo, Tufano, Maria Antonietta, Ignarro, Louis Joseph, and Napoli, Claudio

Published
2008
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28. Additional file 1 of Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts

Author

Marfella, Raffaele, D’Onofrio, Nunzia, Mansueto, Gelsomina, Grimaldi, Vincenzo, Trotta, Maria Consiglia, Sardu, Celestino, Sasso, Ferdinando Carlo, Scisciola, Lucia, Amarelli, Cristiano, Esposito, Salvatore, D’Amico, Michele, Golino, Paolo, De Feo, Marisa, Signoriello, Giuseppe, Paolisso, Pasquale, Gallinoro, Emanuele, Vanderheyden, Marc, Maiello, Ciro, Balestrieri, Maria Luisa, Barbato, Emanuele, Napoli, Claudio, and Paolisso, Giuseppe

Abstract

Additional file 1: Figure S1. Western blot analysis of GlycACE2. Representative immunoblotting of recombinant hACE2 protein (ab151852, Abcam) after in vitro long-term exposure to glucose 120 mM was separated on SDS-PAGE by using 7% gels in reducing and non-reducing conditions and then transferred on nitrocellulose membrane. Membrane was incubated with specific primary antibody against GlycACE2 (1:1000) (#4355, Cell Signaling Technology). Molecular weight indicators are displayed at the center. Figure S2. Ejection fraction, TAPSE, and the E/e′ at week 1 (Basal) and week 48 (follow-up) in nondiabetic and diabetic patients treated with ACE-inhibitors (ACE-I) and angiotensin receptor blocker (ARB). Data are mean ± SD. *P < 0.05 vs non-diabetics, §P < 0.05 vs basal values. Figure S3. GlycACE2 at week 1 (Basal) and week 48 (Follow-up) in the diabetic patients with good glycemic control (HbA1c < 7%) and diabetic patients with poor glycemic control (HbA1c ≥ 7%) treated with ACE-inhibitors (ACE-I) and angiotensin receptor blocker (ARB). Data are mean ± SD. *P < 0.05 vs non-diabetics, §P < 0.05 vs basal values. Figure S4. A Angiotensin-1–9 (Ang-1–9), Ang 1–7, Mas receptor (MasR), Nuclear factor of activated T-cells (NFAT), in explanted hearts (HTX) at week 1 (Basal) and week 48 (Follow-up) from HTX, in nondiabetic and diabetic patients, treated with ACE-inhibitors (ACE-I) and angiotensin receptor blocker (ARB). B Ang-1–9, Ang 1–7, MasR, and NFAT, in explanted hearts (HTX) at week 1 (Basal) and week 48 (Follow-up) from HTX,in the diabetic patients with good glycemic control (HbA1c < 7%) and diabetic patients with poor glycemic control (HbA1c ≥ 7%) treated with ACE-inhibitors (ACE-I) and angiotensin receptor blocker (ARB). Data are mean ± SD. *P < 0.05 vs non-diabetics, §P < 0.05 vs basal values. Figure S5. Fibrosis percentage in explanted hearts (HTX), at week 1 (Basal) and week 48 (follow-up) from HTX, in the diabetic patients with good glycemic control (HbA1c < 7%) and diabetic patients with poor glycemic control (HbA1c ≥ 7%) treated with ACE-inhibitors (ACE-I) and angiotensin receptor blocker (ARB). Data are mean ± SD. *P < 0.05 vs non-diabetics, §P < 0.05 vs basal values. Table S1. Multivariate linear regression analysis with GlycACE2 as dependent variable.

Published
2022
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33. DNA Methylation Profile of the SREBF2 Gene in Human Fetal Aortas

Author

Schiano, Concetta, primary, D’Armiento, Maria, additional, Franzese, Monica, additional, Castaldo, Rossana, additional, Saccone, Gabriele, additional, de Nigris, Filomena, additional, Grimaldi, Vincenzo, additional, Soricelli, Andrea, additional, D’Armiento, Francesco Paolo, additional, Zullo, Fulvio, additional, and Napoli, Claudio, additional

Published
2021
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36. Additional file 2 of Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte

Author

D’Onofrio, Nunzia, Scisciola, Lucia, Sardu, Celestino, Trotta, Maria Consiglia, De Feo, Marisa, Maiello, Ciro, Mascolo, Pasquale, De Micco, Francesco, Turriziani, Fabrizio, Municinò, Emilia, Monetti, Pasquale, Lombardi, Antonio, Napolitano, Maria Gaetana, Marino, Federica Zito, Ronchi, Andrea, Grimaldi, Vincenzo, Hermenean, Anca, Rizzo, Maria Rosaria, Barbieri, Michelangela, Franco, Renato, Campobasso, Carlo Pietro, Napoli, Claudio, Municinò, Maurizio, Paolisso, Giuseppe, Balestrieri, Maria Luisa, and Marfella, Raffaele

Abstract

Additional file 2: Figure S2. Mass spectra of the triply charged hACE2 tryptic peptide 342-357 in the glycated (panel A) and non-glycated (panel B) form. hACE2 is for human Angiotensin Converting enzyme 2 type.

Published
2021
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37. ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis

Author

Infante, Teresa, primary, Franzese, Monica, additional, Ruocco, Antonio, additional, Schiano, Concetta, additional, Affinito, Ornella, additional, Pane, Katia, additional, Memoli, Domenico, additional, Rizzo, Francesca, additional, Weisz, Alessandro, additional, Bontempo, Paola, additional, Grimaldi, Vincenzo, additional, Berrino, Liberato, additional, Soricelli, Andrea, additional, Mauro, Ciro, additional, and Napoli, Claudio, additional

Published
2021
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38. ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis.

Author

Infante, Teresa, Franzese, Monica, Ruocco, Antonio, Schiano, Concetta, Affinito, Ornella, Pane, Katia, Memoli, Domenico, Rizzo, Francesca, Weisz, Alessandro, Bontempo, Paola, Grimaldi, Vincenzo, Berrino, Liberato, Soricelli, Andrea, Mauro, Ciro, and Napoli, Claudio

Subjects
ACUTE coronary syndrome, DNA methylation, METHYLATION, CORONARY disease, T cells, HISTONE methylation, HISTONES, GENE expression
Abstract

Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease. We performed an epigenome-wide analysis of circulating CD4+ and CD8+ T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4+ T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients vs HS. In CD8+ T cells, we identified 613 DMRs associated with 569 annotated genes (28% hyper- and 72% hypo-methylated) in ACS patients as compared to HS. In CD4+vs CD8+ T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes (NFATC1, TCF7, PDGFA, PRKCB, PRKCZ, ABCA1) and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients vs HS (P < 0.001). ABCA1, TCF7, PDGFA, and PRKCZ gene expression was positively associated with CK-MB serum concentrations (r = 0.75, P = 0.03; r = 0.760, P = 0.029; r = 0.72, P = 0.044; r = 0.74, P = 0.035, respectively). This pilot study is the first single-base resolution map of DNA methylome by RRBS in CD4+ and CD8+ T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology. [ABSTRACT FROM AUTHOR]

Published
2022
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42. Integrated analysis of DNA methylation profile of HLA-G gene and imaging in coronary heart disease: Pilot study

Author

Schiano, Concetta, primary, Benincasa, Giuditta, additional, Infante, Teresa, additional, Franzese, Monica, additional, Castaldo, Rossana, additional, Fiorito, Carmela, additional, Mansueto, Gelsomina, additional, Grimaldi, Vincenzo, additional, Della Valle, Giovanni, additional, Fatone, Gerardo, additional, Soricelli, Andrea, additional, Nicoletti, Giovanni Francesco, additional, Ruocco, Antonio, additional, Mauro, Ciro, additional, Salvatore, Marco, additional, and Napoli, Claudio, additional

Published
2020
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46. DNA Methylation Profile of the SREBF2 Gene in Human Fetal Aortas.

Author

Schiano, Concetta, D'Armiento, Maria, Franzese, Monica, Castaldo, Rossana, Saccone, Gabriele, de Nigris, Filomena, Grimaldi, Vincenzo, Soricelli, Andrea, D'Armiento, Francesco Paolo, Zullo, Fulvio, and Napoli, Claudio

Subjects
DNA methylation, AORTA, HUMAN genes, MANN Whitney U Test, DISEASE risk factors, MATERNAL age, EPIGENOMICS
Abstract

Increasing evidence suggests that maternal cholesterol represents an important risk factor for atherosclerotic disease in offspring already during pregnancy, although the underlying mechanisms have not yet been elucidated. Eighteen human fetal aorta samples were collected from the spontaneously aborted fetuses of normal cholesterolemic and hypercholesterolemic mothers. Maternal total cholesterol levels were assessed during hospitalization. DNA methylation profiling of the whole SREBF2 gene CpG island was performed (p value <0.05). The Mann-Whitney U test was used for comparison between the 2 groups. For the first time, our study revealed that in fetal aortas obtained from hypercholesterolemic mothers, the SREBF2 gene shows 4 significant differentially hypermethylated sites in the 5′UTR-CpG island. This finding indicates that more effective long-term primary cardiovascular prevention programs need to be designed for the offspring of mothers with hypercholesterolemia. Further studies should be conducted to clarify the epigenetic mechanisms underlying the association between early atherogenesis and maternal hypercholesterolemia during pregnancy. [ABSTRACT FROM AUTHOR]

Published
2022
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47. ABCA1, TCF7, NFATC1, PRKCZ,and PDGFADNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome vianetwork analysis

Author

Infante, Teresa, Franzese, Monica, Ruocco, Antonio, Schiano, Concetta, Affinito, Ornella, Pane, Katia, Memoli, Domenico, Rizzo, Francesca, Weisz, Alessandro, Bontempo, Paola, Grimaldi, Vincenzo, Berrino, Liberato, Soricelli, Andrea, Mauro, Ciro, and Napoli, Claudio

Abstract

ABSTRACTAcute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease.We performed an epigenome-wide analysis of circulating CD4+and CD8+T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4+T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients vsHS. In CD8+T cells, we identified 613 DMRs associated with 569 annotated genes (28% hyper- and 72% hypo-methylated) in ACS patients as compared to HS. In CD4+vsCD8+T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes (NFATC1, TCF7, PDGFA, PRKCB, PRKCZ, ABCA1) and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients vsHS (P< 0.001). ABCA1, TCF7, PDGFA,and PRKCZgene expression was positively associated with CK-MB serum concentrations (r= 0.75, P= 0.03; r= 0.760, P= 0.029; r= 0.72, P= 0.044; r= 0.74, P= 0.035, respectively).This pilot study is the first single-base resolution map of DNA methylome by RRBS in CD4+and CD8+T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology.

Published
2022
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48. Genetic and epigenetic-sensitive regulatory network in immune response: a putative link between HLA-G and diabetes

Author

Sommese, Linda, primary, Benincasa, Giuditta, additional, Schiano, Concetta, additional, Marfella, Raffaele, additional, Grimaldi, Vincenzo, additional, Sorriento, Antonio, additional, Lucchese, Roberta, additional, Fiorito, Carmela, additional, Sardu, Celestino, additional, Nicoletti, Giovanni Francesco, additional, and Napoli, Claudio, additional

Published
2019
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50. Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte.

Author

D'Onofrio, Nunzia, Scisciola, Lucia, Sardu, Celestino, Trotta, Maria Consiglia, De Feo, Marisa, Maiello, Ciro, Mascolo, Pasquale, De Micco, Francesco, Turriziani, Fabrizio, Municinò, Emilia, Monetti, Pasquale, Lombardi, Antonio, Napolitano, Maria Gaetana, Marino, Federica Zito, Ronchi, Andrea, Grimaldi, Vincenzo, Hermenean, Anca, Rizzo, Maria Rosaria, Barbieri, Michelangela, and Franco, Renato

Subjects
COVID-19, ANGIOTENSIN converting enzyme, SARS-CoV-2, COVID-19 pandemic, PROTEIN domains
Abstract

Rationale: About 50% of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) developed myocardial damage. The mechanisms of direct SARS-CoV-2 cardiomyocyte infection include viral invasion via ACE2-Spike glycoprotein-binding. In DM patients, the impact of glycation of ACE2 on cardiomyocyte invasion by SARS-CoV-2 can be of high importance. Objective: To evaluate the presence of SARS-CoV-2 in cardiomyocytes from heart autopsy of DM cases compared to Non-DM; to investigate the role of DM in SARS-COV-2 entry in cardiomyocytes. Methods and results: We evaluated consecutive autopsy cases, deceased for COVID-19, from Italy between Apr 30, 2020 and Jan 18, 2021. We evaluated SARS-CoV-2 in cardiomyocytes, expression of ACE2 (total and glycosylated form), and transmembrane protease serine protease-2 (TMPRSS2) protein. In order to study the role of diabetes on cardiomyocyte alterations, independently of COVID-19, we investigated ACE2, glycosylated ACE2, and TMPRSS2 proteins in cardiomyocytes from DM and Non-DM explanted-hearts. Finally, to investigate the effects of DM on ACE2 protein modification, an in vitro glycation study of recombinant human ACE2 (hACE2) was performed to evaluate the effects on binding to SARS-CoV-2 Spike protein. The authors included cardiac tissue from 97 autopsies. DM was diagnosed in 37 patients (38%). Fourth-seven out of 97 autopsies (48%) had SARS-CoV-2 RNA in cardiomyocytes. Thirty out of 37 DM autopsy cases (81%) and 17 out of 60 Non-DM autopsy cases (28%) had SARS-CoV-2 RNA in cardiomyocytes. Total ACE2, glycosylated ACE2, and TMPRSS2 protein expressions were higher in cardiomyocytes from autopsied and explanted hearts of DM than Non-DM. In vitro exposure of monomeric hACE2 to 120 mM glucose for 12 days led to non-enzymatic glycation of four lysine residues in the neck domain affecting the protein oligomerization. Conclusions: The upregulation of ACE2 expression (total and glycosylated forms) in DM cardiomyocytes, along with non-enzymatic glycation, could increase the susceptibility to COVID-19 infection in DM patients by favouring the cellular entry of SARS-CoV2. [ABSTRACT FROM AUTHOR]

Published
2021
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