HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm
BackgroundThe etiopathogenesis of abdominal aortic aneurysm (AAA) is still unclarified, but vascular inflammation and matrix metalloproteases activation have a recognized role in AAA development and progression. Circulating lipoproteins are involved in tissue inflammation and repair, particularly th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.935241/full |
| _version_ | 1798002882873655296 |
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| author | Maria Pia Adorni Marcella Palumbo Cinzia Marchi Francesca Zimetti Alice Ossoli Marta Turri Franco Bernini Ivana Hollan Jiří Moláček Vladislav Treska Nicoletta Ronda |
| author_facet | Maria Pia Adorni Marcella Palumbo Cinzia Marchi Francesca Zimetti Alice Ossoli Marta Turri Franco Bernini Ivana Hollan Jiří Moláček Vladislav Treska Nicoletta Ronda |
| author_sort | Maria Pia Adorni |
| collection | DOAJ |
| description | BackgroundThe etiopathogenesis of abdominal aortic aneurysm (AAA) is still unclarified, but vascular inflammation and matrix metalloproteases activation have a recognized role in AAA development and progression. Circulating lipoproteins are involved in tissue inflammation and repair, particularly through the regulation of intracellular cholesterol, whose excess is associated to cell damage and proinflammatory activation. We analyzed lipoprotein metabolism and function in AAA and in control vasculopathic patients, to highlight possible non-atherosclerosis-related, specific abnormalities.MethodsWe measured fluorometrically serum esterified/total cholesterol ratio, as an index of lecithin-cholesterol acyltransferase (LCAT) activity, and cholesteryl ester transfer protein (CETP) activity in patients referred to vascular surgery either for AAA (n=30) or stenotic aortic/peripheral atherosclerosis (n=21) having similar burden of cardiovascular risk factors and disease. We measured high-density lipoprotein (HDL)-cholesterol efflux capacity (CEC), through the ATP-binding cassette G1 (ABCG1) and A1 (ABCA1) pathways and serum cell cholesterol loading capacity (CLC), by radioisotopic and fluorimetric methods, respectively.ResultsWe found higher LCAT (+23%; p < 0.0001) and CETP (+49%; p < 0.0001) activity in AAA sera. HDL ABCG1-CEC was lower (−16%; p < 0.001) and ABCA1-CEC was higher (+31.7%; p < 0.0001) in AAA. Stratification suggests that smoking may partly contribute to these modifications. CEC and CETP activity correlated with CLC only in AAA.ConclusionsWe demonstrated that compared to patients with stenotic atherosclerosis, patients with AAA had altered HDL metabolism and functions involved in their anti-inflammatory and tissue repair activity, particularly through the ABCG1-related intracellular signaling. Clarifying the relevance of this mechanism for AAA evolution might help in developing new diagnostic parameters and therapeutic targets for the early management of this condition. |
| first_indexed | 2024-04-11T12:00:25Z |
| format | Article |
| id | doaj.art-13b20e860bbb483795431d4c285fcdfc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T12:00:25Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-13b20e860bbb483795431d4c285fcdfc2022-12-22T04:24:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.935241935241HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysmMaria Pia Adorni0Marcella Palumbo1Cinzia Marchi2Francesca Zimetti3Alice Ossoli4Marta Turri5Franco Bernini6Ivana Hollan7Jiří Moláček8Vladislav Treska9Nicoletta Ronda10Department of Medicine and Surgery, Unit of Neuroscience, University of Parma, Via Volturno 39/F, Parma, ItalyDepartment of Food and Drug, University of Parma, Parco Area delle Scienze 27/A, Parma, ItalyDepartment of Food and Drug, University of Parma, Parco Area delle Scienze 27/A, Parma, ItalyDepartment of Food and Drug, University of Parma, Parco Area delle Scienze 27/A, Parma, ItalyCentro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, ItalyCentro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, ItalyDepartment of Food and Drug, University of Parma, Parco Area delle Scienze 27/A, Parma, ItalyLillehammer Hospital for Rheumatic Diseases, M. Grundtvigs veg 6, Lillehammer, Norway and Brigham and Women’s Hospital, Cardiology Division, Boston, United StatesDepartment of Vascular Surgery, Faculty of Medicine and University Hospital in Plzen, Charles University Ovocný trh 5 Prague 1, Plzen, CzechiaDepartment of Vascular Surgery, Faculty of Medicine and University Hospital in Plzen, Charles University Ovocný trh 5 Prague 1, Plzen, CzechiaDepartment of Food and Drug, University of Parma, Parco Area delle Scienze 27/A, Parma, ItalyBackgroundThe etiopathogenesis of abdominal aortic aneurysm (AAA) is still unclarified, but vascular inflammation and matrix metalloproteases activation have a recognized role in AAA development and progression. Circulating lipoproteins are involved in tissue inflammation and repair, particularly through the regulation of intracellular cholesterol, whose excess is associated to cell damage and proinflammatory activation. We analyzed lipoprotein metabolism and function in AAA and in control vasculopathic patients, to highlight possible non-atherosclerosis-related, specific abnormalities.MethodsWe measured fluorometrically serum esterified/total cholesterol ratio, as an index of lecithin-cholesterol acyltransferase (LCAT) activity, and cholesteryl ester transfer protein (CETP) activity in patients referred to vascular surgery either for AAA (n=30) or stenotic aortic/peripheral atherosclerosis (n=21) having similar burden of cardiovascular risk factors and disease. We measured high-density lipoprotein (HDL)-cholesterol efflux capacity (CEC), through the ATP-binding cassette G1 (ABCG1) and A1 (ABCA1) pathways and serum cell cholesterol loading capacity (CLC), by radioisotopic and fluorimetric methods, respectively.ResultsWe found higher LCAT (+23%; p < 0.0001) and CETP (+49%; p < 0.0001) activity in AAA sera. HDL ABCG1-CEC was lower (−16%; p < 0.001) and ABCA1-CEC was higher (+31.7%; p < 0.0001) in AAA. Stratification suggests that smoking may partly contribute to these modifications. CEC and CETP activity correlated with CLC only in AAA.ConclusionsWe demonstrated that compared to patients with stenotic atherosclerosis, patients with AAA had altered HDL metabolism and functions involved in their anti-inflammatory and tissue repair activity, particularly through the ABCG1-related intracellular signaling. Clarifying the relevance of this mechanism for AAA evolution might help in developing new diagnostic parameters and therapeutic targets for the early management of this condition.https://www.frontiersin.org/articles/10.3389/fimmu.2022.935241/fullvascular biologyarterial aneurysminflammationlecithin cholesterol acyltransferasecholesteryl ester transfer proteincholesterol efflux |
| spellingShingle | Maria Pia Adorni Marcella Palumbo Cinzia Marchi Francesca Zimetti Alice Ossoli Marta Turri Franco Bernini Ivana Hollan Jiří Moláček Vladislav Treska Nicoletta Ronda HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm Frontiers in Immunology vascular biology arterial aneurysm inflammation lecithin cholesterol acyltransferase cholesteryl ester transfer protein cholesterol efflux |
| title | HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm |
| title_full | HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm |
| title_fullStr | HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm |
| title_full_unstemmed | HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm |
| title_short | HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm |
| title_sort | hdl metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm |
| topic | vascular biology arterial aneurysm inflammation lecithin cholesterol acyltransferase cholesteryl ester transfer protein cholesterol efflux |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.935241/full |
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