Cardiovascular Disease and mTOR Signaling
Open accessAbstract
The cell signaling pathways of the mammalian target of rapamycin (mTOR) are broad in nature but are tightly integrated through the protein complexes of mTORC1 and mTORC2. Although both complexes share some similar subcomponents, mTORC1 is primarily associated with the regulatory protein Raptor, whereas mTORC2 relies on Rictor. Pathways of mTOR that partner with Wnt as well as growth factor signaling are vital for endothelial and cardiomyocyte growth. In mature differentiated endothelial cells and cardiac cells, mTOR activation regulates both apoptotic and autophagic pathways during oxidative stress that can be dependent on the activation of protein kinase B. These protective pathways of mTOR can promote angiogenesis and limit acute cell death to foster cardiac repair and tissue regeneration. However, under some conditions, blockade of mTOR pathways may be necessary to limit vasculopathy and promote microcirculatory flow. Future work that further elucidates the vital regulatory pathways of mTOR can offer new therapeutic insights for the treatment of cardiovascular diseases.
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The TSC1/TSC2 complex is a negative regulator of mTORC1 by controlling the activity of Rheb.
“The TSC1/TSC2 complex is a negative regulator of mTORC1 by controlling the activity of Ras homologue enriched in brain (Rheb).”
From Tuberous Sclerosis Protein 2 (TSC2) Modulates CCN4 Cytoprotection During Apoptotic Amyloid Toxicity in Microglia (2013) · cites this paper as [25]
The Stem cell proliferation section (page not provided) says that phosphorylation of TSC2 results in inhibition of mTOR activity, supporting a negative regulatory role for TSC2. It does not establish that the TSC1/TSC2 complex regulates mTORC1 by controlling Rheb activity. (LLM, conf=0.82)
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Research works printed but not linked: 40
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“One pathway that can modulate mTOR activity is the tuberous sclerosis complex (TSC1, hamartin/ TSC2, tuberin) complex [24, 25].”
BackgroundSelf-citation
- Authors
- Chong, Z. Z., Shang, Y. C., & Maiese, K.
- Affiliations
- Rutgers Cancer Institute (US)
- Corresponding author
- Maiese, Kenneth
- Venue
- Trends in Cardiovascular Medicine
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 21
- Issue
- 5
- Pages
- 151-155
- ISSN
- 1050-1738 (ISSN-L)
- PMC
- PMC3384484
- OpenAlex
- W2007871968
- Cited by
- 87
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 10 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 9 · 2016: 2 · 2015: 9 · 2014: 10 · 2013: 6 · 2012: 9
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Cardiovascular Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS053946)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- mTOR signaling, mTORC1, mTORC2, raptors, Rictor, cardiovascular disease, endothelial cells, cardiomyocytes, Wnt signaling, growth factor signaling, apoptosis, autophagy, oxidative stress, Akt, angiogenesis, cardiac repair, vasculopathy, microcirculation, rapamycin
- MeSH terms
- Cardiovascular Diseases, Humans, Signal Transduction, TOR Serine-Threonine Kinases
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