Mammalian Target of Rapamycin as the Therapeutic Target of Vascular Proliferative Diseases: Past, Present, and Future

Huang, Wei; Zou, Yan; Tian, Ying; Ma, Xiaofeng; Zhou, Qianxiang; Li, Zhenyu; Gong, Shaohua; Wang, Aiping

doi:10.1097/fjc.0000000000001208

Cited by 5 publications

(4 citation statements)

References 145 publications

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“…Together, these data clearly indicate that EP4 indirectly promotes S6 phosphorylation (Ser235/236) via the PKA/mTORC1 pathway rather than through PKA directly. Since mTOR as a serine/threonine protein kinase plays an important role in cell proliferation and migration [ 42 , 43 ], its inhibitor rapamycin has been used in clinic to prevent restenosis [ 44 , 45 , 46 , 47 ]. The present study provides a novel insight into the mechanism by which rapamycin attenuates vascular neointimal hyperplasia through downregulation of TN-C.…”

Section: Discussionmentioning

confidence: 99%

The Prostaglandin E2 Receptor EP4 Promotes Vascular Neointimal Hyperplasia through Translational Control of Tenascin C via the cAMP/PKA/mTORC1/rpS6 Pathway

Fang

Bao

et al. 2022

Cells

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Prostaglandin E2 (PGE2) is an important metabolite of arachidonic acid which plays a crucial role in vascular physiology and pathophysiology via its four receptors (EP1-4). However, the role of vascular smooth muscle cell (VSMC) EP4 in neointimal hyperplasia is largely unknown. Here we showed that VSMC-specific deletion of EP4 (VSMC-EP4) ameliorated, while VSMC-specific overexpression of human EP4 promoted, neointimal hyperplasia in mice subjected to femoral artery wire injury or carotid artery ligation. In vitro studies revealed that pharmacological activation of EP4 promoted, whereas inhibition of EP4 suppressed, proliferation and migration of primary-cultured VSMCs. Mechanically, EP4 significantly increased the protein expression of tenascin C (TN-C), a pro-proliferative and pro-migratory extracellular matrix protein, at the translational level. Knockdown of TN-C markedly suppressed EP4 agonist-induced VSMC proliferation and migration. Further studies uncovered that EP4 upregulated TN-C protein expression via the PKA/mTORC1/Ribosomal protein S6 (rpS6) pathway. Together, our findings demonstrate that VSMC EP4 increases TN-C protein expression to promote neointimal hyperplasia via the PKA-mTORC1-rpS6 pathway. Therefore, VSMC EP4 may represent a potential therapeutic target for vascular restenosis.

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Section: Discussionmentioning

confidence: 99%

The Prostaglandin E2 Receptor EP4 Promotes Vascular Neointimal Hyperplasia through Translational Control of Tenascin C via the cAMP/PKA/mTORC1/rpS6 Pathway

Fang

Bao

et al. 2022

Cells

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“…Rapamycin, also known as sirolimus, is an inhibitor of the mTOR complex 1 (mTORC1), which can suppress downstream signaling and the associated protein synthesis, thereby reducing angiogenesis [ 115 ]. Propranolol, a first-line medicine for treating hemangiomas with great effectiveness, mainly involves the interaction between adrenergic and VEGF pathways [ 116 ].…”

Section: Nanotechnology Applying In Therapy Of Vascular Anomaliesmentioning

confidence: 99%

Recent advances in nanomaterial-driven strategies for diagnosis and therapy of vascular anomalies

Geng,

Zou,

et al. 2024

J Nanobiotechnol

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Nanotechnology has demonstrated immense potential in various fields, especially in biomedical field. Among these domains, the development of nanotechnology for diagnosing and treating vascular anomalies has garnered significant attention. Vascular anomalies refer to structural and functional anomalies within the vascular system, which can result in conditions such as vascular malformations and tumors. These anomalies can significantly impact the quality of life of patients and pose significant health concerns. Nanoscale contrast agents have been developed for targeted imaging of blood vessels, enabling more precise identification and characterization of vascular anomalies. These contrast agents can be designed to bind specifically to abnormal blood vessels, providing healthcare professionals with a clearer view of the affected areas. More importantly, nanotechnology also offers promising solutions for targeted therapeutic interventions. Nanoparticles can be engineered to deliver drugs directly to the site of vascular anomalies, maximizing therapeutic effects while minimizing side effects on healthy tissues. Meanwhile, by incorporating functional components into nanoparticles, such as photosensitizers, nanotechnology enables innovative treatment modalities such as photothermal therapy and photodynamic therapy. This review focuses on the applications and potential of nanotechnology in the imaging and therapy of vascular anomalies, as well as discusses the present challenges and future directions. Graphical Abstract

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“…Mammalian target of rapamycin complex 1 (mTORC1) is an evolutionarily conserved serine/threonine protein kinase responsible for the regulation of cell proliferation and metabolism ( Battaglioni et al, 2022 ; Huang et al, 2022 ). The activity of mTORC1 is regulated or feedback-regulated by a variety of intracellular signaling factors, such as growth factors, protein levels, energy levels, and intracellular oxygen partial pressure ( Wang et al, 2021 ; Li et al, 2022 ).…”

Section: Primary Targets or Signalling Pathways Mediated By Lsd1mentioning

confidence: 99%

Mechanisms of carcinogenic activity triggered by lysine-specific demethylase 1A

Yang

Zang

et al. 2022

Front. Pharmacol.

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Epigenetics has emerged as a prime focus area in the field of cancer research. Lysine-specific demethylase 1A (LSD1), the first discovered histone demethylase, is mainly responsible for catalysing demethylation of histone 3 lysine 4 (H3K4) and H3K9 to activate or inhibit gene transcription. LSD1 is abnormally expressed in various cancers and participates in cancer proliferation, apoptosis, metastasis, invasion, drug resistance and other processes by interacting with regulatory factors. Therefore, it may serve as a potential therapeutic target for cancer. This review summarises the major oncogenic mechanisms mediated by LSD1 and provides a reference for developing novel and efficient anticancer strategies targeting LSD1.

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Mammalian Target of Rapamycin as the Therapeutic Target of Vascular Proliferative Diseases: Past, Present, and Future

Cited by 5 publications

References 145 publications

The Prostaglandin E2 Receptor EP4 Promotes Vascular Neointimal Hyperplasia through Translational Control of Tenascin C via the cAMP/PKA/mTORC1/rpS6 Pathway

The Prostaglandin E2 Receptor EP4 Promotes Vascular Neointimal Hyperplasia through Translational Control of Tenascin C via the cAMP/PKA/mTORC1/rpS6 Pathway

Recent advances in nanomaterial-driven strategies for diagnosis and therapy of vascular anomalies

Mechanisms of carcinogenic activity triggered by lysine-specific demethylase 1A

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