Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach
Abstract Background Diabetes mellitus (DM) accelerates the progression of aortic stenosis (AS), but how their underlying molecular mechanisms interact is not clear. Moreover, whether DM contributes to clinically relevant sex-differences in AS is unknown. In this work we aim to characterize the sex-s...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-10-01
|
| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-023-02009-w |
| _version_ | 1797454002265260032 |
|---|---|
| author | Ernesto Martín-Núñez Miriam Goñi-Olóriz Lara Matilla Mattie Garaikoetxea Laura Mourino-Alvarez Adela Navarro Amaya Fernández-Celis Ibai Tamayo Alicia Gainza Virginia Álvarez Rafael Sádaba María G. Barderas Eva Jover Natalia López-Andrés |
| author_facet | Ernesto Martín-Núñez Miriam Goñi-Olóriz Lara Matilla Mattie Garaikoetxea Laura Mourino-Alvarez Adela Navarro Amaya Fernández-Celis Ibai Tamayo Alicia Gainza Virginia Álvarez Rafael Sádaba María G. Barderas Eva Jover Natalia López-Andrés |
| author_sort | Ernesto Martín-Núñez |
| collection | DOAJ |
| description | Abstract Background Diabetes mellitus (DM) accelerates the progression of aortic stenosis (AS), but how their underlying molecular mechanisms interact is not clear. Moreover, whether DM contributes to clinically relevant sex-differences in AS is unknown. In this work we aim to characterize the sex-specific profile of major pathological mechanisms fundamental to aortic valve (AV) degeneration in AS patients with or without concomitant DM. Methods 283 patients with severe AS undergoing surgical valve replacement (27.6% DM, 59.4% men) were recruited. Expression of pathological markers related to AS were thoroughly assessed in AVs and valve interstitial cells (VICs) according to sex and presence of DM. Complementary in vitro experiments in VICs in the presence of high-glucose levels (25 mM) for 24, 48 and 72 h were performed. Results Oxidative stress and metabolic dysfunction markers were increased in AVs from diabetic AS patients compared to non-diabetic patients in both sexes. However, disbalanced oxidative stress and enhanced inflammation were more predominant in AVs from male AS diabetic patients. Osteogenic markers were exclusively increased in the AVs of diabetic women. Basal characterization of VICs confirmed that oxidative stress, inflammation, calcification, and metabolic alteration profiles were increased in diabetic VICs with sex-specific differences. VICs cultured in hyperglycemic-like conditions triggered inflammatory responses in men, whereas in women rapid and higher production of pro-osteogenic molecules. Conclusions DM produces sex-specific pathological phenotypes in AV of AS patients. Importantly, women with diabetes are more prone to develop AV calcification. DM should be considered as a risk factor in AS especially in women. |
| first_indexed | 2024-03-09T15:30:57Z |
| format | Article |
| id | doaj.art-2cd3d7f1dab649a9ad0cd270d6ed8337 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-03-09T15:30:57Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-2cd3d7f1dab649a9ad0cd270d6ed83372023-11-26T12:15:47ZengBMCCardiovascular Diabetology1475-28402023-10-0122111510.1186/s12933-023-02009-wInfluence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approachErnesto Martín-Núñez0Miriam Goñi-Olóriz1Lara Matilla2Mattie Garaikoetxea3Laura Mourino-Alvarez4Adela Navarro5Amaya Fernández-Celis6Ibai Tamayo7Alicia Gainza8Virginia Álvarez9Rafael Sádaba10María G. Barderas11Eva Jover12Natalia López-Andrés13Cardiovascular Translational Research, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA)Cardiovascular Translational Research, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA)Cardiovascular Translational Research, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA)Cardiovascular Translational Research, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA)Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM)Cardiovascular Translational Research, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA)Cardiovascular Translational Research, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA)Research Methodology Unit, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNACardiovascular Translational Research, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA)Cardiovascular Translational Research, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA)Cardiovascular Translational Research, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA)Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM)Cardiovascular Translational Research, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA)Cardiovascular Translational Research, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA)Abstract Background Diabetes mellitus (DM) accelerates the progression of aortic stenosis (AS), but how their underlying molecular mechanisms interact is not clear. Moreover, whether DM contributes to clinically relevant sex-differences in AS is unknown. In this work we aim to characterize the sex-specific profile of major pathological mechanisms fundamental to aortic valve (AV) degeneration in AS patients with or without concomitant DM. Methods 283 patients with severe AS undergoing surgical valve replacement (27.6% DM, 59.4% men) were recruited. Expression of pathological markers related to AS were thoroughly assessed in AVs and valve interstitial cells (VICs) according to sex and presence of DM. Complementary in vitro experiments in VICs in the presence of high-glucose levels (25 mM) for 24, 48 and 72 h were performed. Results Oxidative stress and metabolic dysfunction markers were increased in AVs from diabetic AS patients compared to non-diabetic patients in both sexes. However, disbalanced oxidative stress and enhanced inflammation were more predominant in AVs from male AS diabetic patients. Osteogenic markers were exclusively increased in the AVs of diabetic women. Basal characterization of VICs confirmed that oxidative stress, inflammation, calcification, and metabolic alteration profiles were increased in diabetic VICs with sex-specific differences. VICs cultured in hyperglycemic-like conditions triggered inflammatory responses in men, whereas in women rapid and higher production of pro-osteogenic molecules. Conclusions DM produces sex-specific pathological phenotypes in AV of AS patients. Importantly, women with diabetes are more prone to develop AV calcification. DM should be considered as a risk factor in AS especially in women.https://doi.org/10.1186/s12933-023-02009-wAortic stenosisSex-differenceHeart valve diseaseType 2 diabetesAortic valve disease |
| spellingShingle | Ernesto Martín-Núñez Miriam Goñi-Olóriz Lara Matilla Mattie Garaikoetxea Laura Mourino-Alvarez Adela Navarro Amaya Fernández-Celis Ibai Tamayo Alicia Gainza Virginia Álvarez Rafael Sádaba María G. Barderas Eva Jover Natalia López-Andrés Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach Cardiovascular Diabetology Aortic stenosis Sex-difference Heart valve disease Type 2 diabetes Aortic valve disease |
| title | Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach |
| title_full | Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach |
| title_fullStr | Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach |
| title_full_unstemmed | Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach |
| title_short | Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach |
| title_sort | influence of diabetes mellitus on the pathological profile of aortic stenosis a sex based approach |
| topic | Aortic stenosis Sex-difference Heart valve disease Type 2 diabetes Aortic valve disease |
| url | https://doi.org/10.1186/s12933-023-02009-w |
| work_keys_str_mv | AT ernestomartinnunez influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach AT miriamgonioloriz influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach AT laramatilla influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach AT mattiegaraikoetxea influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach AT lauramourinoalvarez influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach AT adelanavarro influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach AT amayafernandezcelis influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach AT ibaitamayo influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach AT aliciagainza influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach AT virginiaalvarez influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach AT rafaelsadaba influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach AT mariagbarderas influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach AT evajover influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach AT natalialopezandres influenceofdiabetesmellitusonthepathologicalprofileofaorticstenosisasexbasedapproach |