Ageing induced vascular smooth muscle cell senescence in atherosclerosis

Uryga, Anna; Bennett, Martin R.

doi:10.1113/jp270923

Cited by 119 publications

(85 citation statements)

References 82 publications

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“…1,38 For example, Sahin et al demonstrated that Tert -/-mice exhibit early aging and heart failure. 39 It was observed in our experiments that telomere length was not significantly different between cardiac tissues harvested from newborn, adult, and aged mice, which may have been caused by maintenance of telomerase activity in aged rodents.…”

Section: Discussionmentioning

confidence: 99%

Rejuvenation of Cardiac Tissue Developed from Reprogrammed Aged Somatic Cells

Cheng

Peng

Zhang

et al. 2017

Rejuvenation Research

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Induced pluripotent stem cells (iPSCs) derived via somatic cell reprogramming have been reported to reset aged somatic cells to a more youthful state, characterized by elongated telomeres, a rearranged mitochondrial network, reduced oxidative stress, and restored pluripotency. However, it is still unclear whether the reprogrammed aged somatic cells can function normally as embryonic stem cells (ESCs) during development and be rejuvenated. In the current study, we applied the aggregation technique to investigate whether iPSCs derived from aged somatic cells could develop normally and be rejuvenated. iPSCs derived from bone marrow myeloid cells of 2-month-old (2 M) and 18-month-old (18 M) C57BL/6-Tg (CAG-EGFP)1Osb/J mice were aggregated with embryos derived from wild-type ICR mice to produce chimeras (referred to as 2 M CA and 18 M CA, respectively). Our observations focused on comparing the ability of the iPSCs derived from 18 M and 2 M bone marrow cells to develop rejuvenated cardiac tissue (the heart is the most vital organ during aging). The results showed an absence of p16 and p53 upregulation, telomere length shortening, and mitochondrial gene expression and deletion in 18 M CA, whereas slight changes in mitochondrial ultrastructure, cytochrome C oxidase activity, ATP production, and reactive oxygen species production were observed in CA cardiac tissues. The data implied that all of the aging characteristics observed in the newborn cardiac tissue of 18 M CA were comparable with those of 2 M CA newborn cardiac tissue. This study provides the first direct evidence of the aging-related characteristics of cardiac tissue developed from aged iPSCs, and our observations demonstrate that partial rejuvenation can be achieved by reprogramming aged somatic cells to a pluripotent state.

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Section: Discussionmentioning

confidence: 99%

Rejuvenation of Cardiac Tissue Developed from Reprogrammed Aged Somatic Cells

Cheng

Peng

Zhang

et al. 2017

Rejuvenation Research

View full text Add to dashboard Cite

show abstract

“…For instance, advanced atherosclerotic plaques contain VSMCs which exhibit the classical SASP. The secretion of MMPs and inflammatory cytokines leads to plaque instability, with the risk of rupture and thrombosis (7,13). Nevertheless, besides SASP, senescent cells can sustain atherosclerosis with other mechanisms still not completely known.…”

Section: Vascular Smooth Muscle Cells (Vsmcs)mentioning

confidence: 99%

MicroRNAs orchestrating senescence of endothelial and vascular smooth muscle cells

Colpani

Spinetti

2019

Vascular Biology

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During organism aging, the process of cellular senescence is triggered by critical stressors such as DNA damage, oncogenes, oxidative stress, and telomere erosion, and vascular cells are not exempted. Senescent cells stop proliferating but remain metabolically active producing pro-inflammatory signals in the environment collectively named senescenceassociated secretory phenotype (SASP) that contribute to the amplification of the response to the neighbor and distant cells. Although the shift toward senescence is protective against tumors and needed during wound healing, the accumulation of senescent cells during aging due to an impairment of the immune system deputed to their clearance, can predispose to diseases of the cardiovascular system such as atherosclerosis. In this short review, we describe the main features of senescence of endothelial and smooth muscle cells and focus on the role non-coding RNAs of the microRNAs class in controlling this process. Finally, we discuss the potential of new strategies based on senescence removal in counteracting vascular disease burden.

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“…4 Most mature and healthy VSMCs are of the contractile phenotype and exhibit a relatively high contractile capability and a low proliferation ability. 5 However, different physiological and pathological stimuli may cause the VSMC phenotypic switch, which leads to the proliferation, migration, and synthesis of excessive extracellular matrices. 6 These effects result in pathological changes to tissues and organs.…”

Section: Introductionmentioning

confidence: 99%

Aortic dissection is associated with reduced polycystin-1 expression, an abnormality that leads to increased ERK phosphorylation in vascular smooth muscle cells

Feng

Zhang

et al. 2016

Eur J Histochem

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The vascular smooth muscle cell (VSMC) phenotypic switch is a key pathophysiological change in various cardiovascular diseases, such as aortic dissection (AD), with a high morbidity. Polycystin-1 (PC1) is significantly downregulated in the VSMCs of AD patients. PC1 is an integral membrane glycoprotein and kinase that regulates different biological processes, including cell proliferation, apoptosis, and cell polarity. However, the role of PC1 in intracellular signaling pathways remains poorly understood. In this study, PC1 downregulation in VSMCs promoted the expression of SM22, ACTA2 and calponin 1 (CNN1) proteins. Furthermore, PC1 downregulation in VSMCs upregulated phospho-MEK, phospho-ERK and myc, but did not change phospho-JNK and phospho-p38. These findings suggest that the MEK/ERK/myc signaling pathway is involved in PC1-mediated human VSMC phenotypic switch. Opposite results were observed when an ERK inhibitor was used in VSMCs downregulated by PC1. When the C-terminal domain of PC1 (PC1 C-tail) was overexpressed in VSMCs, the expression levels of phosphor-ERK, myc, SM22, ACTA2 and CNN1 proteins were downregulated. The group with the overexpressed mutant protein (S4166A) in the PC1 C-tail showed similar results to the group with the downregulated PC1 in VSMCs. These results suggest that the Ser at the 4166 site in PC1 is crucial in the PC1 mediated MEK/ERK/myc signaling pathway, which might be the key pathophysiological cause of AD.

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Ageing induced vascular smooth muscle cell senescence in atherosclerosis

Cited by 119 publications

References 82 publications

Rejuvenation of Cardiac Tissue Developed from Reprogrammed Aged Somatic Cells

Rejuvenation of Cardiac Tissue Developed from Reprogrammed Aged Somatic Cells

MicroRNAs orchestrating senescence of endothelial and vascular smooth muscle cells

Aortic dissection is associated with reduced polycystin-1 expression, an abnormality that leads to increased ERK phosphorylation in vascular smooth muscle cells

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