ArticleCirculation research2013
AKT2 confers protection against aortic aneurysms and dissections.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 93 citations in OpenAlex.
- Mouse models of aortic dissection induced by β-aminopropionitrile combined with angiotensin II and the changes in their gut microbiota.BMC microbiology · 2025Article
- Risk of artery dissection during systemic exposure to vascular endothelial growth factor pathway inhibitors.Clinical and translational science · 2024Article
- Enhancing Exosomal Delivery to Abdominal Aortic Aneurysms using Magnetically Responsive Chemotactic Nanomotors for Elastic Matrix Regenerative Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Acute aortic catastrophe caused by cardiovascular oncological manipulation by tyrosine kinase inhibitors with immune checkpoint blockades: a case report and literature review.European heart journal. Case reports · 2024Article
- Vascular Endothelial Growth Factor Inhibitors and the Risk of Aortic Aneurysm and Aortic Dissection.JAMA network open · 2024Article
- The prognostic value of preoperative systemic inflammatory response index in predicting outcomes of acute type A aortic dissection patients underwent surgical treatment.Frontiers in immunology · 2024Article
- CRP deposition in human abdominal aortic aneurysm is associated with transcriptome alterations toward aneurysmal pathogenesis: insights fromFrontiers in immunology · 2024Article
- Promising Novel Therapies in the Treatment of Aortic and Visceral Aneurysms.Journal of clinical medicine · 2023Review
- Progression of Thoracic Aortic Dissection Is Aggravated by the hsa_circ_0007386/miR-1271-5P/IGF1R/AKT Axis via Induction of Arterial Smooth Muscle Cell Apoptosis.Biomedicines · 2023Article
- Aortic Stress Activates an Adaptive Program in Thoracic Aortic Smooth Muscle Cells That Maintains Aortic Strength and Protects Against Aneurysm and Dissection in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Acute aortic dissection caused by fruquintinib for metastatic colorectal cancer-a case report and literature review.Translational cancer research · 2023Article
- Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.International journal of molecular sciences · 2023Review
- Review
- mRNA, lncRNA, and circRNA expression profiles in a new aortic dissection murine model induced by hypoxia and Ang II.Frontiers in cardiovascular medicine · 2022Article
- Role of PCK2 in the proliferation of vascular smooth muscle cells in neointimal hyperplasia.International journal of biological sciences · 2022Article
- Targeting Ferroptosis as a Novel Approach to Alleviate Aortic Dissection.International journal of biological sciences · 2022Article
- Article
- MiR-126-5p promotes contractile switching of aortic smooth muscle cells by targeting VEPH1 and alleviates Ang II-induced abdominal aortic aneurysm in mice.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- AKT2 regulates endothelial-mediated coagulation homeostasis and promotes intrathrombotic recanalization and thrombus resolution in a mouse model of venous thrombosis.Journal of thrombosis and thrombolysis · 2020Article
- Therapeutic Effect of Rapamycin on Aortic Dissection in Mice.International journal of molecular sciences · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
rationaleAortic aneurysm and dissection (AAD) are major diseases of the adult aorta caused by progressive medial degeneration of the aortic wall. Although the overproduction of destructive factors promotes tissue damage and disease progression, the role of protective pathways is unknown.
objectiveIn this study, we examined the role of AKT2 in protecting the aorta from developing AAD. METHODS AND
resultsAKT2 and phospho-AKT levels were significantly downregulated in human thoracic AAD tissues, especially within the degenerative medial layer. Akt2-deficient mice showed abnormal elastic fibers and reduced medial thickness in the aortic wall. When challenged with angiotensin II, these mice developed aortic aneurysm, dissection, and rupture with features similar to those in humans, in both thoracic and abdominal segments. Aortas from Akt2-deficient mice displayed profound tissue destruction, apoptotic cell death, and inflammatory cell infiltration that were not observed in aortas from wild-type mice. In addition, angiotensin II-infused Akt2-deficient mice showed significantly elevated expression of matrix metalloproteinase-9 (MMP-9) and reduced expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). In cultured human aortic vascular smooth muscle cells, AKT2 inhibited the expression of MMP-9 and stimulated the expression of TIMP-1 by preventing the binding of transcription factor forkhead box protein O1 to the MMP-9 and TIMP-1 promoters.
conclusionsImpaired AKT2 signaling may contribute to increased susceptibility to the development of AAD. Our findings provide evidence of a mechanism that underlies the protective effects of AKT2 on the aortic wall and that may serve as a therapeutic target in the prevention of AAD.
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