Downregulation of Pin1 in human atherosclerosis and its association with vascular smooth muscle cell senescence

Ye, Meng; Duan, Rundan; Yuan, Kai; Chen, Jiaquan; Liang, Wei; Zhou, Zhaoxiong; Zhang, Lan

doi:10.1016/j.jvs.2017.09.006

Cited by 17 publications

(11 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Atherosclerosis is recognized as a chronic inflammatory condition ( 339 ) and atherosclerotic plaques show cellular senescence ( 340 , 341 ). Cytokines are involved in all stages of the pathogenesis of atherosclerosis, having both pro- or anti-atherogenic effects ( 342 , 343 ).…”

Section: Age-related Diseasesmentioning

confidence: 99%

Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

et al. 2018

View full text Add to dashboard Cite

Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called “inflamm-aging.” Despite research there is no clear understanding about the causes of “inflamm-aging” that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer’s disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with “inflammageing” or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis.

show abstract

Section: Age-related Diseasesmentioning

confidence: 99%

Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Klotho inhibits the expression of lectin-like oxidized LDL receptor-1 (LOX-1) via the PI3K/AKT/eNOS pathway [81], and the Klotho-induced inhibition of insulin/ IGF-1 signaling increases the resistance to oxidative stress, potentially improving the anti-senescence properties of Klotho [82]. The level of Pin1 protein is decreased in human atherosclerotic tissues, and adenoviral-mediated Pin1 overexpression rescued cellular senescence in atherosclerotic HVSMCs, with the concurrent downregulation of P53, P21, phosphorylated retinoblastoma (p-pRB), and P65, and the upregulation of cyclin subfamilies (cyclin B, D, and E) and cyclin-dependent kinase subfamilies (CDK2, 4, and 6), whereas Pin1 knockdown has the opposite effects [83], indicating that these factors can be potent modulators of HVSMCs senescence. Similarly, FGF21 [84], SIRT1 and SIRT6 [85,86], and CoQ10H2 [87] protected cells from oxidative stressinduced cell damage, including premature cell senescence, intracellular accumulation of ROS, and increased DNA damage.…”

Section: Potential Therapeutic Targets Of Cell Senescencementioning

confidence: 99%

The emerging role of cell senescence in atherosclerosis

Zheng

Wang

et al. 2020

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

Cell senescence is a fundamental mechanism of aging and appears to play vital roles in the onset and prognosis of cardiovascular disease, fibrotic pulmonary disease, liver disease and tumor. Moreover, an increasing body of evidence shows that cell senescence plays an indispensable role in the formation and development of atherosclerosis. Multiple senescent cell types are associated with atherosclerosis, senescent human vascular endothelial cells participated in atherosclerosis via regulating the level of endothelin-1 (ET-1), nitric oxide (NO), angiotensin II and monocyte chemoattractant protein-1 (MCP-1), senescent human vascular smooth muscle cells-mediated plaque instability and vascular calcification via regulating the expression level of BMP-2, OPN, Runx-2 and inflammatory molecules, and senescent macrophages impaired cholesterol efflux and promoted the development of senescent-related cardiovascular diseases. This review summarizes the characteristics of cell senescence and updates the molecular mechanisms underlying cell senescence. Moreover, we also discuss the recent advances on the molecular mechanisms that can potentially regulate the development and progression of atherosclerosis.

show abstract

“…Since the identification of the importance of human peptidyl-prolyl cis/trans isomerase Pin1 in Alzheimer’s disease [104] through the modulation of Tau protein [45], Pin1 and juglone have gained considerable attention. As a result, and largely through studies using juglone, Pin1 has also been implicated in a wide variety of clinical conditions including immune response [105], allergy [106], cancer [107,108], hyperparathyroidism [109], rheumatoid arthritis [110], vascular pathology [111,112,113,114,115], diabetes [116], Parkinson’s disease [117], and cardiac fibrosis [118,119,120]. There are numerous review articles already available on Pin1, and thus interested readers should refer to these articles that are found in PubMed and other sources.…”

Section: Role Of Juglone As An Inhibitor Of Peptidyl-prolyl Cis/trmentioning

confidence: 99%

Juglone in Oxidative Stress and Cell Signaling

2019

View full text Add to dashboard Cite

Juglone (5-hydroxyl-1,4-naphthoquinone) is a phenolic compound found in walnuts. Because of the antioxidant capacities of phenolic compounds, juglone may serve to combat oxidative stress, thereby protecting against the development of various diseases and aging processes. However, being a quinone molecule, juglone could also act as a redox cycling agent and produce reactive oxygen species. Such prooxidant properties of juglone may confer health effects, such as by killing cancer cells. Further, recent studies revealed that juglone influences cell signaling. Notably, juglone is an inhibitor of Pin1 (peptidyl-prolyl cis/trans isomerase) that could regulate phosphorylation of Tau, implicating potential effects of juglone in Alzheimer’s disease. Juglone also activates mitogen-activated protein kinases that could promote cell survival, thereby protecting against conditions such as cardiac injury. This review describes recent advances in the understanding of the effects and roles of juglone in oxidative stress and cell signaling.

show abstract

Downregulation of Pin1 in human atherosclerosis and its association with vascular smooth muscle cell senescence

Abstract: Altogether this work supports a role for Pin1 as a vital modulator of VSMC senescence, thereby providing a novel target for regulation and control of atherosclerosis.

Cited by 17 publications

References 32 publications

Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

The emerging role of cell senescence in atherosclerosis

Juglone in Oxidative Stress and Cell Signaling

Contact Info

Product

Resources

About