Orsini, Roberta Clara (2021) Plasma phospholipid dysregulation in patients with cystathionine β- synthase deficiency. [Tesi di dottorato]
Anteprima |
Testo
Orsini_RobertaClara_33.pdf Download (1MB) | Anteprima |
| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Plasma phospholipid dysregulation in patients with cystathionine β- synthase deficiency |
| Autori: | Autore Email Orsini, Roberta Clara roberta.orsini@alice.it |
| Data: | 11 Febbraio 2021 |
| Numero di pagine: | 43 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Medicina Clinica e Chirurgia |
| Dottorato: | Terapie avanzate biomediche e chirurgiche |
| Ciclo di dottorato: | 33 |
| Coordinatore del Corso di dottorato: | nome email Di Minno, Giovanni diminno@unina.it |
| Tutor: | nome email Di Minno, Matteo Nicola Dario [non definito] |
| Data: | 11 Febbraio 2021 |
| Numero di pagine: | 43 |
| Parole chiave: | Homocystinuria, plasma untargeted lipidomics, S-adenosylmethionine, Sadenosylhomocysteine, phosphatidylethanolamine-N-methyltransferase |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/10 - Biochimica Area 03 - Scienze chimiche > CHIM/03 - Chimica generale e inorganica Area 03 - Scienze chimiche > CHIM/06 - Chimica organica Area 06 - Scienze mediche > MED/09 - Medicina interna |
| Depositato il: | 24 Feb 2021 09:46 |
| Ultima modifica: | 07 Giu 2023 10:29 |
| URI: | http://www.fedoa.unina.it/id/eprint/13986 |
Abstract
Patients with cystathionine β-synthase deficiency (CBSD) exhibit extremely high circulating levels of homocysteine (Hcy) and clinical signs and symptoms whose pathophysiological understanding is poorly elucidated. The aberrant Hcy metabolism could lead to the redox imbalance and oxidative stress resulting in elevated lipid peroxidation. Although phospholipid metabolism is key for a variety of cell functions, no information is available about lipidomic profile in CBSD patients. We have characterized plasma lipidome in CBSD patients and related lipid abnormalities with reactions underlying enhanced homocysteine levels. Using an untargeted lipidomic approach, changes in phospholipid metabolism were determined by comparing the plasma of 11 CBSD patients with that of 11 healthy subjects (CTRL). CBSD patients had a higher medium and long-chain polyunsaturated fatty acids (PUFA) content in phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) species (p=0.02), and depletion of phosphatidylcholine (PC; p=0.02) and of lysophosphatidylcholine (LPC; p=0.003) species containing docosahexaenoic acid (DHA), suggesting impaired phosphatidylethanolamine-N-methyltransferase (PEMT) activity. PEMT converts PE into PC using methyl group by S-adenosylmethionine (SAM) thus converted in S-adenosylhomocysteine (SAH). Whole blood SAM and SAH concentrations by liquid chromatography tandem mass spectrometry were 1.4-fold (p=0.015) and 5.3-fold (p=0.003) higher in CBSD patients than in CTRL. A positive correlation between SAM/SAH and PC/PE ratios (r=0.520; p=0.019) was found. Our findings reveals e novel biochemical alteration in CBSD patients consisting in depletion of PC and LPC species containing DHA and accumulation of PUFA in PE and LPE. Variations in plasma SAM and SAH concentration are associated with such phospholipid dysregulation. Given the key role of DHA in thrombosis prevention, reduction of PC species containing DHA in CBSD patients provides a new direction to understand the poor cardiovascular outcome of patients with CBSD.
Downloads
Downloads per month over past year
Actions (login required)
 |
Modifica documento |
