prikaz prve stranice dokumenta Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice
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Scientific paper - Original scientific paper
Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice
Cardiovascular Diabetology, 22 (2023), 1; 327. https://doi.org/10.1186/s12933-023-02064-3
Amor, Melina; Bianco, Valentina; Buerger, Martin; Lechleitner, Margarete; Vujić, Nemanja; Dobrijević, Anja; Akhmetshina, Alena; Pirchheim, Anita; Schwarz, Birgit; Pessentheiner, Ariane R.; Baumgartner, Franziska; Rampitsch, Katharina; Schauer, Silvia; Klobučar, Iva; Degoricija, Vesna; Pregartner, Gudrun; Kummer, Daniel; Svecla, Monika; Sommer, Gerhard; Kolb, Dagmar; Holzapfel, Gerhard A.; Hoefler, Gerald; Frank, Saša; Norata, Giuseppe Danilo; Kratky, Dagmar More authors...

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Amor, M., Bianco, V., Buerger, M., Lechleitner, M., Vujić, N., Dobrijević, A. ... Kratky, D. (2023). Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice. Cardiovascular Diabetology, 22. (1). doi: 10.1186/s12933-023-02064-3

Amor, Melina, et al. "Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice." Cardiovascular Diabetology, vol. 22, no. 1, 2023. https://doi.org/10.1186/s12933-023-02064-3

Amor, Melina, Valentina Bianco, Martin Buerger, Margarete Lechleitner, Nemanja Vujić, Anja Dobrijević, Alena Akhmetshina, et al. "Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice." Cardiovascular Diabetology 22, no. 1 (2023). https://doi.org/10.1186/s12933-023-02064-3

Amor, M., et al. (2023) 'Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice', Cardiovascular Diabetology, 22(1). doi: 10.1186/s12933-023-02064-3

Amor M, Bianco V, Buerger M, Lechleitner M, Vujić N, Dobrijević A, and sur.. Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice. Cardiovascular Diabetology [Internet]. 2023 November 28 [cited 2024 September 09];22(1). doi: 10.1186/s12933-023-02064-3

M. Amor, et al., "Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice", Cardiovascular Diabetology, vol. 22, no. 1, November 2023. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:105:552054. [Accessed: 09 September 2024]

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Metadata
Title (english)Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice
AuthorMelina Amor
AuthorValentina Bianco
AuthorMartin Buerger
AuthorMargarete Lechleitner
AuthorNemanja Vujić
AuthorAnja Dobrijević
AuthorAlena Akhmetshina
AuthorAnita Pirchheim
AuthorBirgit Schwarz
AuthorAriane R. Pessentheiner
AuthorFranziska Baumgartner
AuthorKatharina Rampitsch
AuthorSilvia Schauer
AuthorIva Klobučar
AuthorVesna Degoricija
AuthorGudrun Pregartner
AuthorDaniel Kummer
AuthorMonika Svecla
AuthorGerhard Sommer
AuthorDagmar Kolb
AuthorGerhard A. Holzapfel
AuthorGerald Hoefler
AuthorSaša Frank
AuthorGiuseppe Danilo Norata
AuthorDagmar Kratky
Author's institutionUniversity of Zagreb
School of Medicine
(Department of Internal Medicine)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Internal Medicine
Abstract (english)
Background: Matrix metalloproteinase 12 (MMP12) is a macrophage-secreted protein that is massively upregulated as a pro-inflammatory factor in metabolic and vascular tissues of mice and humans suffering from cardiometabolic diseases (CMDs). However, the molecular mechanisms explaining the contributions of MMP12 to CMDs are still unclear. Methods: We investigated the impact of MMP12 deficiency on CMDs in a mouse model that mimics human disease by simultaneously developing adipose tissue inflammation, insulin resistance, and atherosclerosis. To this end, we generated and characterized low-density lipoprotein receptor (Ldlr)/Mmp12-double knockout (DKO) mice fed a high-fat sucrose- and cholesterol-enriched diet for 16-20 weeks. Results: DKO mice showed lower cholesterol and plasma glucose concentrations and improved insulin sensitivity compared with LdlrKO mice. Untargeted proteomic analyses of epididymal white adipose tissue revealed that inflammation- and fibrosis-related pathways were downregulated in DKO mice. In addition, genetic deletion of MMP12 led to alterations in immune cell composition and a reduction in plasma monocyte chemoattractant protein-1 in peripheral blood which indicated decreased low-grade systemic inflammation. Aortic en face analyses and staining of aortic valve sections demonstrated reduced atherosclerotic plaque size and collagen content, which was paralleled by an improved relaxation pattern and endothelial function of the aortic rings and more elastic aortic sections in DKO compared to LdlrKO mice. Shotgun proteomics revealed upregulation of anti-inflammatory and atheroprotective markers in the aortas of DKO mice, further supporting our data. In humans, MMP12 serum concentrations were only weakly associated with clinical and laboratory indicators of CMDs. Conclusion: We conclude that the genetic deletion of MMP12 ameliorates obesity-induced low-grade inflammation, white adipose tissue dysfunction, biomechanical properties of the aorta, and the development of atherosclerosis. Therefore, therapeutic strategies targeting MMP12 may represent a promising approach to combat CMDs.
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review
Publication versionPublished version
Journal titleCardiovascular Diabetology
Numberingvol. 22, no. 1, 327
e-ISSN1475-2840
DOIhttps://doi.org/10.1186/s12933-023-02064-3
URN:NBNurn:nbn:hr:105:552054
Publication2023-11-28
Document URLhttps://cardiab.biomedcentral.com/articles/10.1186/s12933-023-02064-3
Type of resourceText
Access conditionsOpen access
Terms of useLicence Attribution 4.0 International (CC BY 4.0) icon
Created on2024-04-09 08:11:30