Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach

Cardiovascular Diabetology

Research

Virginia Álvarez¹  Lara Matilla¹  Adela Navarro¹  Eva Jover¹  Mattie Garaikoetxea¹  Alicia Gainza¹  Amaya Fernández-Celis¹  Rafael Sádaba¹  Miriam Goñi-Olóriz¹  Ernesto Martín-Núñez¹  Natalia López-Andrés¹  Laura Mourino-Alvarez²  María G. Barderas²  Ibai Tamayo³ 

[1] Cardiovascular Translational Research, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), C/Irunlarrea 3, 31008, Pamplona, Spain;Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo, Spain;Hospital Nacional de Paraplejicos, Servicio de Salud de Castilla-La Mancha (SESCAM), Toledo, Spain;Research Methodology Unit, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain;

关键词: Aortic stenosis;    Sex-difference;    Heart valve disease;    Type 2 diabetes;    Aortic valve disease;   

DOI  :  10.1186/s12933-023-02009-w

 received in 2023-05-29, accepted in 2023-09-26,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundDiabetes 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.Methods283 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.ResultsOxidative 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.ConclusionsDM 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.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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