TRIM65 promotes vascular smooth muscle cell phenotypic transformation by activating PI3K/Akt/mTOR signaling during atherogenesis

Zhou, Zhi-Xiang; Ma, Xiao-Feng; Xiong, Wen-Hao; Ren, Zhong; Jiang, Miao; Deng, Nian-Hua; Zhou, Bo-Bin; Liu, Hui-Ting; Zhou, Kun; Hu, Heng-Jing; Tang, Hui-Fang; Zheng, He; Jiang, Zhi-Sheng

doi:10.1016/j.atherosclerosis.2023.117430

Cited by 3 publications

(2 citation statements)

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“…On the other hand, the high levels of IL-17 in vascular tissue activate NFκB-dependent pathways, raising the tissue levels of IL-6 and chemokines [ 26 ]. Beyond this specific form of cytokine-driven destabilization and inflammation of the endothelium, mTOR has several ways of producing local damage [ 27 ]. The activation of the mTORC1 complex can promote the production of IL-12 and IL-23 in dendritic cells, helping to recruit more activated T lymphocytes [ 27 ].…”

Section: Key Evidence Of the Pivotal Role Of Mtor Non-skin Manifestat...mentioning

confidence: 99%

“…Beyond this specific form of cytokine-driven destabilization and inflammation of the endothelium, mTOR has several ways of producing local damage [ 27 ]. The activation of the mTORC1 complex can promote the production of IL-12 and IL-23 in dendritic cells, helping to recruit more activated T lymphocytes [ 27 ]. Also, mTORC activation participates in the proliferation of smooth muscle cells and regulates oxidative stress, which is frequently enhanced by high levels of IL-6 and TNF-α [ 28 ].…”

Section: Key Evidence Of the Pivotal Role Of Mtor Non-skin Manifestat...mentioning

confidence: 99%

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Pivotal Role of mTOR in Non-Skin Manifestations of Psoriasis

Joo,

Karsulovic,

Sore

et al. 2024

IJMS

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Psoriasis is a chronic inflammatory condition affecting 2% of the Western population. It includes diverse manifestations influenced by genetic predisposition, environmental factors, and immune status. The sustained activation of mTOR is a key element in psoriasis pathogenesis, leading to an uncontrolled proliferation of cytokines. Furthermore, mTOR activation has been linked with the transition from psoriasis to non-skin manifestations such as psoriatic arthritis and cardiovascular events. While therapies targeting pro-inflammatory cytokines have shown efficacy, additional pathways may offer therapeutic potential. The PI3K/Akt/mTOR pathway, known for its role in cell growth, proliferation, and metabolism, has emerged as a potential therapeutic target in psoriasis. This review explores the relevance of mTOR in psoriasis pathophysiology, focusing on its involvement in cutaneous and atheromatous plaque proliferation, psoriatic arthritis, and cardiovascular disease. The activation of mTOR promotes keratinocyte and synovial cell proliferation, contributing to plaque formation and joint inflammation. Moreover, mTOR activation may exacerbate the cardiovascular risk by promoting pro-inflammatory cytokine production and dysregulation lipid and glucose metabolism. The inhibition of mTOR has shown promise in preclinical studies, reducing skin inflammation and plaque proliferation. Furthermore, mTOR inhibition may mitigate cardiovascular risk by modulating cholesterol metabolism and attenuating atherosclerosis progression. Understanding the role of mTOR in psoriasis, psoriatic arthritis, and cardiovascular disease provides insight into the potential treatment avenues and sheds light on the complex interplay of the immune and metabolic pathways in these conditions.

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Section: Key Evidence Of the Pivotal Role Of Mtor Non-skin Manifestat...mentioning

confidence: 99%