High-Intensity Statins Promote PCSK9 Secretion and aortic valve calcification in patients with severe aortic stenosis: In vitro and clinical evidence
Aortic stenosis (AS) is the most common valvular disease, characterized by progressive fibro-calcific remodeling of the aortic leaflets, leading to increased morbidity and mortality. It is now well known that statins influence the production of proprotein convertase subtilisin/kexin type 9 (PCSK9),...
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Elsevier
2025-05-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825001628 |
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| author | Veronika A. Myasoedova Matteo Franchi Donato De Giorgi Alice Bonomi Vincenza Valerio Sergio Pirola Niccolò Andreani Valentina Rusconi Francesca Bertolini Ilaria Massaiu Gianluca Pontone Paolo Poggio |
| author_facet | Veronika A. Myasoedova Matteo Franchi Donato De Giorgi Alice Bonomi Vincenza Valerio Sergio Pirola Niccolò Andreani Valentina Rusconi Francesca Bertolini Ilaria Massaiu Gianluca Pontone Paolo Poggio |
| author_sort | Veronika A. Myasoedova |
| collection | DOAJ |
| description | Aortic stenosis (AS) is the most common valvular disease, characterized by progressive fibro-calcific remodeling of the aortic leaflets, leading to increased morbidity and mortality. It is now well known that statins influence the production of proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn is linked to calcification. Here, we found that statins significantly increased, in a dose dependent manner, both PCSK9 secretion and valve interstitial cell (VIC) calcification, in vitro. These effects were blunted by PCSK9 genetic knock-down or by PCSK9 antibody neutralization. In AS patients, contrast-enhanced computed tomography evaluation showed a higher aortic valve calcium (AVC) content in patients on high-intensity statins compared to low-intensity ones, with no significant difference between low-intensity statin and non-users. At follow-up, high-intensity statin users exhibited a higher annual AVC accumulation compared to low-intensity statins and non-users. In a real-world scenario, high-intensity statin therapy was associated with a 30 % increased rate of hospitalization for non-rheumatic aortic valve disease. Our findings highlight the need for further investigation into the intricate relationship between statin therapy and aortic valve health to identify the optimal lipid-lowering strategy in the management of patients at risk of developing or afflicted by AS. |
| format | Article |
| id | doaj-art-8c771e5d2cb347ef9d435e1a2e8cbad7 |
| institution | OA Journals |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-8c771e5d2cb347ef9d435e1a2e8cbad72025-08-20T02:18:50ZengElsevierPharmacological Research1096-11862025-05-0121510773710.1016/j.phrs.2025.107737High-Intensity Statins Promote PCSK9 Secretion and aortic valve calcification in patients with severe aortic stenosis: In vitro and clinical evidenceVeronika A. Myasoedova0Matteo Franchi1Donato De Giorgi2Alice Bonomi3Vincenza Valerio4Sergio Pirola5Niccolò Andreani6Valentina Rusconi7Francesca Bertolini8Ilaria Massaiu9Gianluca Pontone10Paolo Poggio11Centro Cardiologico Monzino IRCCS, Milan 20138, ItalyCentro Cardiologico Monzino IRCCS, Milan 20138, Italy; Unit of Biostatistics, Epidemiology and Public Health, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan 20126, ItalyCentro Cardiologico Monzino IRCCS, Milan 20138, ItalyCentro Cardiologico Monzino IRCCS, Milan 20138, ItalyCentro Cardiologico Monzino IRCCS, Milan 20138, ItalyCentro Cardiologico Monzino IRCCS, Milan 20138, ItalyUnit of Biostatistics, Epidemiology and Public Health, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan 20126, ItalyCentro Cardiologico Monzino IRCCS, Milan 20138, ItalyCentro Cardiologico Monzino IRCCS, Milan 20138, ItalyCentro Cardiologico Monzino IRCCS, Milan 20138, ItalyCentro Cardiologico Monzino IRCCS, Milan 20138, Italy; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20122, ItalyCentro Cardiologico Monzino IRCCS, Milan 20138, Italy; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20122, Italy; Correspondence to: Head of Unit for the Study of Aortic, Valvular, and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, Milan 20138, Italy.Aortic stenosis (AS) is the most common valvular disease, characterized by progressive fibro-calcific remodeling of the aortic leaflets, leading to increased morbidity and mortality. It is now well known that statins influence the production of proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn is linked to calcification. Here, we found that statins significantly increased, in a dose dependent manner, both PCSK9 secretion and valve interstitial cell (VIC) calcification, in vitro. These effects were blunted by PCSK9 genetic knock-down or by PCSK9 antibody neutralization. In AS patients, contrast-enhanced computed tomography evaluation showed a higher aortic valve calcium (AVC) content in patients on high-intensity statins compared to low-intensity ones, with no significant difference between low-intensity statin and non-users. At follow-up, high-intensity statin users exhibited a higher annual AVC accumulation compared to low-intensity statins and non-users. In a real-world scenario, high-intensity statin therapy was associated with a 30 % increased rate of hospitalization for non-rheumatic aortic valve disease. Our findings highlight the need for further investigation into the intricate relationship between statin therapy and aortic valve health to identify the optimal lipid-lowering strategy in the management of patients at risk of developing or afflicted by AS.http://www.sciencedirect.com/science/article/pii/S1043661825001628Statin intensityPCSK9Aortic valve calcificationAortic valve disease hospitalization |
| spellingShingle | Veronika A. Myasoedova Matteo Franchi Donato De Giorgi Alice Bonomi Vincenza Valerio Sergio Pirola Niccolò Andreani Valentina Rusconi Francesca Bertolini Ilaria Massaiu Gianluca Pontone Paolo Poggio High-Intensity Statins Promote PCSK9 Secretion and aortic valve calcification in patients with severe aortic stenosis: In vitro and clinical evidence Pharmacological Research Statin intensity PCSK9 Aortic valve calcification Aortic valve disease hospitalization |
| title | High-Intensity Statins Promote PCSK9 Secretion and aortic valve calcification in patients with severe aortic stenosis: In vitro and clinical evidence |
| title_full | High-Intensity Statins Promote PCSK9 Secretion and aortic valve calcification in patients with severe aortic stenosis: In vitro and clinical evidence |
| title_fullStr | High-Intensity Statins Promote PCSK9 Secretion and aortic valve calcification in patients with severe aortic stenosis: In vitro and clinical evidence |
| title_full_unstemmed | High-Intensity Statins Promote PCSK9 Secretion and aortic valve calcification in patients with severe aortic stenosis: In vitro and clinical evidence |
| title_short | High-Intensity Statins Promote PCSK9 Secretion and aortic valve calcification in patients with severe aortic stenosis: In vitro and clinical evidence |
| title_sort | high intensity statins promote pcsk9 secretion and aortic valve calcification in patients with severe aortic stenosis in vitro and clinical evidence |
| topic | Statin intensity PCSK9 Aortic valve calcification Aortic valve disease hospitalization |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825001628 |
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