Endothelial Dysfunction May Link Interatrial Septal Abnormalities and MTHFR-Inherited Defects to Cryptogenic Stroke Predisposition
We explored the significance of the L-Arginine/asymmetric dimethylarginine (L-Arg/ADMA) ratio as a biomarker of endothelial dysfunction in stroke patients. To this aim, we evaluated the correlation, in terms of severity, between the degree of endothelial dysfunction (by L-Arg/ADMA ratio), the methyl...
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MDPI AG
2020-06-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/6/861 |
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| author | Luca Sgarra Alessandro Santo Bortone Maria Assunta Potenza Carmela Nacci Maria Antonietta De Salvia Tommaso Acquaviva Emanuela De Cillis Marco Matteo Ciccone Massimo Grimaldi Monica Montagnani |
| author_facet | Luca Sgarra Alessandro Santo Bortone Maria Assunta Potenza Carmela Nacci Maria Antonietta De Salvia Tommaso Acquaviva Emanuela De Cillis Marco Matteo Ciccone Massimo Grimaldi Monica Montagnani |
| author_sort | Luca Sgarra |
| collection | DOAJ |
| description | We explored the significance of the L-Arginine/asymmetric dimethylarginine (L-Arg/ADMA) ratio as a biomarker of endothelial dysfunction in stroke patients. To this aim, we evaluated the correlation, in terms of severity, between the degree of endothelial dysfunction (by L-Arg/ADMA ratio), the methylene tetrahydrofolate reductase (MTHFR) genotype, and the interatrial septum (IAS) phenotype in subject with a history of stroke. <b>Methods and Results:</b> L-Arg, ADMA, and MTHFR genotypes were evaluated; the IAS phenotype was assessed by transesophageal echocardiography. Patients were grouped according to the severity of IAS defects and the residual enzymatic activity of MTHFR-mutated variants, and values of L-Arg/ADMA ratio were measured in each subgroup. Of 57 patients, 10 had a septum integrum (SI), 38 a patent foramen ovale (PFO), and 9 an ostium secundum (OS). The L-Arg/ADMA ratio differed across septum phenotypes (<i>p</i> ≤ 0.01), and was higher in SI than in PFO or OS patients (<i>p</i> ≤ 0.05, <i>p</i> ≤ 0.01, respectively). In the PFO subgroup a negative correlation was found between the L-Arg/ADMA ratio and PFO tunnel length/height ratio (<i>p</i> ≤ 0.05; r = − 0.37; R2 = 0.14). Interestingly, the L-Arg/ADMA ratio varied across MTHFR genotypes (<i>p</i> ≤ 0.0001) and was lower in subgroups carrying the most impaired enzyme with respect to patients carrying the conservative MTHFR (<i>p</i> ≤ 0.0001, <i>p</i> ≤ 0.05, respectively). Consistently, OS patients carried the most dysfunctional MTHFR genotypes, whereas SI patients the least ones. <b>Conclusions:</b> A low L-Arg/ADMA ratio correlates with impaired activity of MTHFR and with the jeopardized IAS phenotype along a severity spectrum encompassing OS, PFO with long/tight tunnel, PFO with short/large tunnel, and SI. This infers that genetic MTHFR defects may underlie endothelial dysfunction-related IAS abnormalities, and predispose to a cryptogenic stroke. Our findings emphasize the role of the L-Arg/ADMA ratio as a reliable marker of stroke susceptibility in carriers of IAS abnormalities, and suggest its potential use both as a diagnostic tool and as a decision aid for therapy. |
| first_indexed | 2024-03-10T19:21:25Z |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T19:21:25Z |
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| spelling | doaj.art-00a830fb4423418287feda93bd66f2112023-11-20T02:53:36ZengMDPI AGBiomolecules2218-273X2020-06-0110686110.3390/biom10060861Endothelial Dysfunction May Link Interatrial Septal Abnormalities and MTHFR-Inherited Defects to Cryptogenic Stroke PredispositionLuca Sgarra0Alessandro Santo Bortone1Maria Assunta Potenza2Carmela Nacci3Maria Antonietta De Salvia4Tommaso Acquaviva5Emanuela De Cillis6Marco Matteo Ciccone7Massimo Grimaldi8Monica Montagnani9Department of Biomedical Sciences and Human Oncology—Section of Pharmacology, Medical School, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation—Section of Cardiovascular Diseases, Medical School, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Biomedical Sciences and Human Oncology—Section of Pharmacology, Medical School, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Biomedical Sciences and Human Oncology—Section of Pharmacology, Medical School, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Biomedical Sciences and Human Oncology—Section of Pharmacology, Medical School, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation—Section of Cardiovascular Diseases, Medical School, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation—Section of Cardiovascular Diseases, Medical School, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation—Section of Cardiovascular Diseases, Medical School, University of Bari “Aldo Moro”, 70124 Bari, ItalyGeneral Hospital “F. Miulli” Acquaviva delle Fonti, 70021 Bari, ItalyDepartment of Biomedical Sciences and Human Oncology—Section of Pharmacology, Medical School, University of Bari “Aldo Moro”, 70124 Bari, ItalyWe explored the significance of the L-Arginine/asymmetric dimethylarginine (L-Arg/ADMA) ratio as a biomarker of endothelial dysfunction in stroke patients. To this aim, we evaluated the correlation, in terms of severity, between the degree of endothelial dysfunction (by L-Arg/ADMA ratio), the methylene tetrahydrofolate reductase (MTHFR) genotype, and the interatrial septum (IAS) phenotype in subject with a history of stroke. <b>Methods and Results:</b> L-Arg, ADMA, and MTHFR genotypes were evaluated; the IAS phenotype was assessed by transesophageal echocardiography. Patients were grouped according to the severity of IAS defects and the residual enzymatic activity of MTHFR-mutated variants, and values of L-Arg/ADMA ratio were measured in each subgroup. Of 57 patients, 10 had a septum integrum (SI), 38 a patent foramen ovale (PFO), and 9 an ostium secundum (OS). The L-Arg/ADMA ratio differed across septum phenotypes (<i>p</i> ≤ 0.01), and was higher in SI than in PFO or OS patients (<i>p</i> ≤ 0.05, <i>p</i> ≤ 0.01, respectively). In the PFO subgroup a negative correlation was found between the L-Arg/ADMA ratio and PFO tunnel length/height ratio (<i>p</i> ≤ 0.05; r = − 0.37; R2 = 0.14). Interestingly, the L-Arg/ADMA ratio varied across MTHFR genotypes (<i>p</i> ≤ 0.0001) and was lower in subgroups carrying the most impaired enzyme with respect to patients carrying the conservative MTHFR (<i>p</i> ≤ 0.0001, <i>p</i> ≤ 0.05, respectively). Consistently, OS patients carried the most dysfunctional MTHFR genotypes, whereas SI patients the least ones. <b>Conclusions:</b> A low L-Arg/ADMA ratio correlates with impaired activity of MTHFR and with the jeopardized IAS phenotype along a severity spectrum encompassing OS, PFO with long/tight tunnel, PFO with short/large tunnel, and SI. This infers that genetic MTHFR defects may underlie endothelial dysfunction-related IAS abnormalities, and predispose to a cryptogenic stroke. Our findings emphasize the role of the L-Arg/ADMA ratio as a reliable marker of stroke susceptibility in carriers of IAS abnormalities, and suggest its potential use both as a diagnostic tool and as a decision aid for therapy.https://www.mdpi.com/2218-273X/10/6/861endothelial dysfunctionL-Arg/ADMAPFOMTHFRcryptogenic stroke |
| spellingShingle | Luca Sgarra Alessandro Santo Bortone Maria Assunta Potenza Carmela Nacci Maria Antonietta De Salvia Tommaso Acquaviva Emanuela De Cillis Marco Matteo Ciccone Massimo Grimaldi Monica Montagnani Endothelial Dysfunction May Link Interatrial Septal Abnormalities and MTHFR-Inherited Defects to Cryptogenic Stroke Predisposition Biomolecules endothelial dysfunction L-Arg/ADMA PFO MTHFR cryptogenic stroke |
| title | Endothelial Dysfunction May Link Interatrial Septal Abnormalities and MTHFR-Inherited Defects to Cryptogenic Stroke Predisposition |
| title_full | Endothelial Dysfunction May Link Interatrial Septal Abnormalities and MTHFR-Inherited Defects to Cryptogenic Stroke Predisposition |
| title_fullStr | Endothelial Dysfunction May Link Interatrial Septal Abnormalities and MTHFR-Inherited Defects to Cryptogenic Stroke Predisposition |
| title_full_unstemmed | Endothelial Dysfunction May Link Interatrial Septal Abnormalities and MTHFR-Inherited Defects to Cryptogenic Stroke Predisposition |
| title_short | Endothelial Dysfunction May Link Interatrial Septal Abnormalities and MTHFR-Inherited Defects to Cryptogenic Stroke Predisposition |
| title_sort | endothelial dysfunction may link interatrial septal abnormalities and mthfr inherited defects to cryptogenic stroke predisposition |
| topic | endothelial dysfunction L-Arg/ADMA PFO MTHFR cryptogenic stroke |
| url | https://www.mdpi.com/2218-273X/10/6/861 |
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