Cells in Atherosclerosis: Focus on Cellular Senescence from Basic Science to Clinical Practice

Molnár, Andrea Ágnes; Pásztor, Dorottya Tímea; Tarcza, Zsófia; Merkely, Béla

doi:10.3390/ijms242417129

Cited by 2 publications

(2 citation statements)

References 178 publications

(341 reference statements)

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“…Network overlaps between these functions are shown in Table 2 . The results indicate that vitamin D's genomic signaling regulates protein–protein interactions involved in atherosclerosis, efferocytosis (B) ( 86 , 87 ), macro-autophagy (C) ( 88 ), macrophage autophagy (D) ( 89 , 90 ), macrophage polarization (E) ( 91 , 92 ), cellular senescence (F) ( 93 ), ER stress response (G) ( 94 ), tissue homeostasis (H) ( 95 ), innate immunity (I) ( 96 ). caveola-mediated endocytosis (J) ( 97 ), and apoptosis (K) ( 98 ).…”

Section: Resultsmentioning

confidence: 99%

Effects of vitamin D signaling in cardiovascular disease: centrality of macrophage polarization

Fliri,

Kajiji

2024

Front. Cardiovasc. Med.

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Among the leading causes of natural death are cardiovascular diseases, cancer, and respiratory diseases. Factors causing illness include genetic predisposition, aging, stress, chronic inflammation, environmental factors, declining autophagy, and endocrine abnormalities including insufficient vitamin D levels. Inconclusive clinical outcomes of vitamin D supplements in cardiovascular diseases demonstrate the need to identify cause-effect relationships without bias. We employed a spectral clustering methodology capable of analyzing large diverse datasets for examining the role of vitamin D's genomic and non-genomic signaling in disease in this study. The results of this investigation showed the following: (1) vitamin D regulates multiple reciprocal feedback loops including p53, macrophage autophagy, nitric oxide, and redox-signaling; (2) these regulatory schemes are involved in over 2,000 diseases. Furthermore, the balance between genomic and non-genomic signaling by vitamin D affects autophagy regulation of macrophage polarization in tissue homeostasis. These findings provide a deeper understanding of how interactions between genomic and non-genomic signaling affect vitamin D pharmacology and offer opportunities for increasing the efficacy of vitamin D-centered treatment of cardiovascular disease and healthy lifespans.

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Section: Resultsmentioning

confidence: 99%

Effects of vitamin D signaling in cardiovascular disease: centrality of macrophage polarization

Fliri,

Kajiji

2024

Front. Cardiovasc. Med.

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“…The age-related diseases are progressive disorders which commonly involve both inflammatory changes and fibrotic degeneration. Typically, these diseases also are associated with the accumulation of senescent cells with inflammatory and degenerative changes, such as in atherosclerosis, chronic obstructive lung disease (COPD), coronary artery disease (CAD), and Alzheimer’s disease (AD) [ 70 – 73 ] as well as in fibrotic diseases, e.g., in idiopathic pulmonary disease (IPF), cardiac fibrosis, and systemic sclerosis [ 70 , 74 , 75 ]. There exists a significant crosstalk between senescent cells and inflammatory cells in the pathogenesis of many age-related diseases, e.g., via the control of the expression of inhibitory checkpoint proteins.…”

Section: Pd-1/pd-l1 Signaling Is Augmented In Many Age-related Diseasesmentioning

confidence: 99%

The role of the immunosuppressive PD-1/PD-L1 checkpoint pathway in the aging process and age-related diseases

Salminen

2024

J Mol Med

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The accumulation of senescent cells within tissues is a hallmark of the aging process. Senescent cells are also commonly present in many age-related diseases and in the cancer microenvironment. The escape of abnormal cells from immune surveillance indicates that there is some defect in the function of cytotoxic immune cells, e.g., CD8+ T cells and natural killer (NK) cells. Recent studies have revealed that the expression of programmed death-ligand 1 (PD-L1) protein is abundantly increased in senescent cells. An increase in the amount of PD-L1 protein protects senescent cells from clearance by the PD-1 checkpoint receptor in cytotoxic immune cells. In fact, the activation of the PD-1 receptor suppresses the cytotoxic properties of CD8+ T and NK cells, promoting a state of immunosenescence. The inhibitory PD-1/PD-L1 checkpoint pathway acts in cooperation with immunosuppressive cells; for example, activation of PD-1 receptor can enhance the differentiation of regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC), and M2 macrophages, whereas the cytokines secreted by immunosuppressive cells stimulate the expression of the immunosuppressive PD-L1 protein. Interestingly, many signaling pathways known to promote cellular senescence and the aging process are crucial stimulators of the expression of PD-L1 protein, e.g., epigenetic regulation, inflammatory mediators, mTOR-related signaling, cGAS-STING pathway, and AhR signaling. It seems that the inhibitory PD-1/PD-L1 immune checkpoint axis has a crucial role in the accumulation of senescent cells and thus it promotes the aging process in tissues. Thus, the blockade of the PD-1/PD-L1 checkpoint signaling might be a potential anti-aging senolytic therapy. Key messages Senescent cells accumulate within tissues during aging and age-related diseases. Senescent cells are able to escape immune surveillance by cytotoxic immune cells. Expression of programmed death-ligand 1 (PD-L1) markedly increases in senescent cells. Age-related signaling stimulates the expression of PD-L1 protein in senescent cells. Inhibitory PD-1/PD-L1 checkpoint pathway suppresses clearance of senescent cells.

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Cells in Atherosclerosis: Focus on Cellular Senescence from Basic Science to Clinical Practice

Cited by 2 publications

References 178 publications

Effects of vitamin D signaling in cardiovascular disease: centrality of macrophage polarization

Effects of vitamin D signaling in cardiovascular disease: centrality of macrophage polarization

The role of the immunosuppressive PD-1/PD-L1 checkpoint pathway in the aging process and age-related diseases

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