Biotech
Study Shows Silencing of AnxA8 Protein Reduces Atherosclerosis Progression in Mice
A study by CIBER, IIS-FJD, and IIB Sant Pau highlights annexin A8 (AnxA8) as a key player in atherosclerosis progression. AnxA8 upregulation in human and murine plaques promotes leukocyte and platelet adhesion. Its inhibition reduces plaque burden, suggesting a potential therapeutic target to slow disease progression and prevent cardiovascular events.
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Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids and leukocytes in the arterial wall. In addition, this disease and its complications are one of the main causes of mortality in the adult population.
In this context, several teams from the Centro de Investigación Biomédica en Red (CIBER), the Fundación Jiménez Díaz Health Research Institute (IIS-FJD) and the Institut d’Investigacions Biomèdiques (IIB) Sant Pau in Barcelona have carried out a study on the role of the annexin A8 protein (AnxA8) in the development and progression of atherosclerotic lesions. The work, published in Clinical and Translational Medicine, highlights the role of AnxA8 in the recruitment of circulating cells to the vascular wall.
“This pathology consists of the progressive accumulation of cholesterol and inflammatory cells in the arterial wall, giving rise to atherosclerotic plaque, which in advanced stages can cause death due to a myocardial infarction or stroke,” explained Luis M. Blanco Colio, researcher at the CIBER of Cardiovascular Diseases (CIBERCV) and the Vascular Pathology Laboratory of the IIS-FJD, who directed the study.
The work has revealed an increase in the expression of annexin A8 (AnxA8) in both human and murine atherosclerotic plaques, highlighting this protein as a key mediator in the progression of atherosclerosis. “Our results demonstrate that AnxA8 participates in the regulation of leukocyte and platelet adhesion in the arterial wall, which favors the development and progression of atherosclerotic lesions,” added the researcher.
“Our results demonstrate that AnxA8 participates in the regulation of leukocyte and platelet adhesion in the arterial wall, which favors the development and progression of atherosclerotic lesions.”
“The specific inhibition of AnxA8 expression in endothelial cells decreases the atherosclerotic burden in animal models, which could indicate that therapeutic interventions aimed at reducing AnxA8 expression could delay the progression of atherosclerosis towards future cardiovascular events,” said Nerea Méndez Barbero, from IIS-FJD.
“The results obtained in human samples and animal models, together with those obtained in endothelial cell cultures, have allowed us to understand the mechanism by which AnxA8 is involved in the development and progression of atherosclerosis,” they highlighted.
The study was carried out at the Jiménez Díaz Foundation Health Research Institute in Madrid, the Sant Pau Biomedical Research Institute in Barcelona, the National Centre for Cardiovascular Research (CNIC), in collaboration with international institutions such as INSERM in Paris and the University of Muenster in Germany.
Atherosclerosis study key results
RNA-Seq revealed that annexin A8 (AnxA8) is one of the most significantly upregulated genes in atherosclerotic aortas from ApoE −/− mice compared with wild-type mice. Furthermore, AnxA8 is also upregulated in human atherosclerotic plaques. Germline deletion of AnxA8 decreased atherosclerotic burden, size, and volume of atherosclerotic plaques in the aortic root . Plaques from ApoE −/− AnxA8 −/− mice were characterized by lower lipid and inflammatory content, smaller necrotic core, thicker fibrous cap, and lower apoptosis compared with those from ApoE −/− AnxA8 +/+ mice.
On the other hand, bone marrow transplantation analysis showed that hematopoietic AnxA8 deficiency had no effect on atherosclerotic progression. Oxidized low-density lipoprotein (ox-LDL) increased AnxA8 expression in murine aortic endothelial cells (MAECs), and in vitro experiments revealed that AnxA8 deficiency in MAECs suppressed ox-LDL-induced expression and secretion of P/E-selectin and CD31, with a concomitant reduction in platelet and leukocyte adhesion.
The study findings demonstrate that annexin A8 (AnxA8) plays a crucial role in the progression of atherosclerosis by modulating endothelial-leukocyte interactions. Thus, it reveals that AnxA8 is upregulated in the aorta of atherosclerosis-prone mice and in human atherosclerotic plaques . Germline AnxA8 deficiency reduces platelet and leukocyte recruitment to activated endothelium, as well as atherosclerotic burden, plaque size, and macrophage accumulation in mice.
Furthermore, AnxA8 regulates the expression of oxLDL-induced adhesion molecules in aortic endothelial cells, suggesting that this protein promotes disease progression through regulating adhesion and immune cell influx into the arterial intima. Endothelial-specific silencing of AnxA8 significantly reduced atherosclerosis progression, implying that therapeutic interventions aimed at decreasing AnxA8 expression could be effective in delaying disease progression.
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(Featured image by Testalize.me via Unsplash)
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First published in GACETA MEDICA. A third-party contributor translated and adapted the article from the original. In case of discrepancy, the original will prevail.
Although we made reasonable efforts to provide accurate translations, some parts may be incorrect. Born2Invest assumes no responsibility for errors, omissions or ambiguities in the translations provided on this website. Any person or entity relying on translated content does so at their own risk. Born2Invest is not responsible for losses caused by such reliance on the accuracy or reliability of translated information. If you wish to report an error or inaccuracy in the translation, we encourage you to contact us
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