ArticleThe Journal of clinical investigation2020
Chronic mTOR activation induces a degradative smooth muscle cell phenotype.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 100 citations in OpenAlex.
- Phenotypic switching of gastrointestinal smooth muscle cells and the regulatory role of macrophages: a literature review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- REDD1 Silencing Aggravates Aortic Dissection and Promotes VSMC Apoptosis with Autophagy-Related Changes.Biomedicines · 2026Article
- The aorta in Marfan syndrome: from molecular mechanisms to mechanobiological dysfunction.Cardiovascular research · 2026Review
- Targeting mTOR to Mitigate Sequelae of Chronic Hypoxia on the Carotid Artery and Cerebral Circulation.Comprehensive Physiology · 2026Article
- Growth arrest of thoracic aortic aneurysms in aging Marfan mice.American journal of physiology. Heart and circulatory physiology · 2026Article
- Mechanics and mechanobiology of arterial development.Biomechanics and modeling in mechanobiology · 2026Review
- Steroid hormone antagonism affords vascular protection in a mouse model of vascular Ehlers-Danlos syndrome.JCI insight · 2026Article
- Transcriptional control of PPP2CB by YAP1 and TEAD1 mediates AMPK inhibition and mTORC1 activation in vascular smooth muscle cells.iScience · 2026Article
- Article
- Integrin-mediated mTOR signaling drives TGF-β overactivity and myxomatous mitral valve degeneration in hypomorphic fibrillin-1 mice.The Journal of clinical investigation · 2025Article
- GSDMD Deficiency Attenuates the Development of Ascending Aortic Dissections in a Novel Mouse Model.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- PP2A Attenuates Thoracic Aneurysm and Dissection in Mouse Models of Marfan Syndrome.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Short-term disruption of TGF-β signaling in adult mice renders the aorta vulnerable to hypertension-induced dissection.JCI insight · 2025Article
- TRPM7 channel activity promotes the pathogenesis of abdominal aortic aneurysms.Nature cardiovascular research · 2025Article
- Heterogeneous Cardiac-Derived and Neural Crest-Derived Aortic Smooth Muscle Cells Exhibit Similar Transcriptional Changes After TGFβ Signaling Disruption.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Hemodynamic disturbance and mTORC1 activation: Unveiling the biomechanical pathogenesis of thoracic aortic aneurysms in Marfan syndrome.Journal of pharmaceutical analysis · 2025Article
- Deficiency of ATF3 facilitates both angiotensin II-induced and spontaneously formed aortic aneurysm and dissection development by activating cGAS-STING pathway.Clinical and translational medicine · 2025Article
- Therapeutic Opportunities of Marfan Syndrome: Current Perspectives.Drug design, development and therapy · 2025Review
- Olfactory Receptors and Aortic Aneurysm: Review of Disease Pathways.Journal of clinical medicine · 2024Review
- Transcriptional regulation of postnatal aortic development.Cells & development · 2024Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 3 institutions in 4 countries.
Funding
Abstract
Smooth muscle cell (SMC) proliferation has been thought to limit the progression of thoracic aortic aneurysm and dissection (TAAD) because loss of medial cells associates with advanced disease. We investigated effects of SMC proliferation in the aortic media by conditional disruption of Tsc1, which hyperactivates mTOR complex 1. Consequent SMC hyperplasia led to progressive medial degeneration and TAAD. In addition to diminished contractile and synthetic functions, fate-mapped SMCs displayed increased proteolysis, endocytosis, phagocytosis, and lysosomal clearance of extracellular matrix and apoptotic cells. SMCs acquired a limited repertoire of macrophage markers and functions via biogenesis of degradative organelles through an mTOR/β-catenin/MITF-dependent pathway, but were distinguishable from conventional macrophages by an absence of hematopoietic lineage markers and certain immune effectors even in the context of hyperlipidemia. Similar mTOR activation and induction of a degradative SMC phenotype in a model of mild TAAD due to Fbn1 mutation greatly worsened disease with near-uniform lethality. The finding of increased lysosomal markers in medial SMCs from clinical TAAD specimens with hyperplasia and matrix degradation further supports the concept that proliferation of degradative SMCs within the media causes aortic disease, thus identifying mTOR-dependent phenotypic modulation as a therapeutic target for combating TAAD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.