Endothelial Extracellular Vesicles Produced by Senescent Cells: Pathophysiological Role in the Cardiovascular Disease Associated with all Types of Diabetes Mellitus

Carracedo, Julia; Alique, Matilde; Ramírez-Carracedo, Rafael; Bodega, Guillermo; Ramı́rez, Rafael

doi:10.2174/1570161116666180820115726

Cited by 30 publications

(21 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…p53 plays a vital role in the endothelium environment and contributes to the maintenance of endothelial homeostasis. However, senescent endothelial cells change their morphological and functional characteristics and cannot correctly regulate repairing and regenerative activities of endothelial progenitor cells (EPCs) [110]. The p53-p21 cip1 pathway appears to be more responsive than the p16-Rb pathway for the induction of endothelial cell senescence.…”

Section: Metabolic Disordersmentioning

confidence: 99%

Role of p53 in the Regulation of Cellular Senescence

et al. 2020

View full text Add to dashboard Cite

The p53 transcription factor plays a critical role in cellular responses to stress. Its activation in response to DNA damage leads to cell growth arrest, allowing for DNA repair, or directs cellular senescence or apoptosis, thereby maintaining genome integrity. Senescence is a permanent cell-cycle arrest that has a crucial role in aging, and it also represents a robust physiological antitumor response, which counteracts oncogenic insults. In addition, senescent cells can also negatively impact the surrounding tissue microenvironment and the neighboring cells by secreting pro-inflammatory cytokines, ultimately triggering tissue dysfunction and/or unfavorable outcomes. This review focuses on the characteristics of senescence and on the recent advances in the contribution of p53 to cellular senescence. Moreover, we also discuss the p53-mediated regulation of several pathophysiological microenvironments that could be associated with senescence and its development.Biomolecules 2020, 10, 420 2 of 16 focus on the p53-dependent senescence signaling pathways involved with different stages of senescence and with a consideration for the associated key biomarkers. We also provide an overview on the regulation of p53-mediated cellular senescence in the context of different pathophysiological conditions. Senescence as Cellular Response to StressCellular senescence is defined as a cell state characterized by prolonged and generally irreversible cell-cycle arrest [14] and the acquisition of different phenotypic alterations, including morphological changes, chromatin remodeling, metabolic reprogramming, and secretion of pro-inflammatory factors or SASP (senescence associated secretory phenotypes). These latter count cytokines, growth factors, proteases, and non-soluble extracellular matrix proteins [15]. All these features ultimately limit the replication of both old and damaged cells. Upon physiological conditions, proliferating cells commit to a regular cell cycle [15,16]. On the other hand, both physiological aging, characterized by telomere shortening, and long-term chronic stress, which impairs genomic integrity and stability, could lead to the activation of the senescence pathway [17]. In this sense, the senescence can be viewed as an adaptative response of cells and organisms when exposed to certain unfavorable environmental conditions.Stressors include both intrinsic factors, such as oxidative damage, telomere attrition, hyperproliferation, oncogene activation, and environmental sources, including UV-light, γ-irradiation, and chemotherapeutic drugs [18,19]. Regardless of their origin, the stress factors trigger DNA damage responses (DDR) in the affected cells, which can result in different outcomes, depending on the cell type and the extent of the damage [20]. Mild DNA damage normally induces cell cycle arrest, while severe injury can activate the senescence program or the death programs; the latter includes apoptosis, mitotic catastrophe, autophagy, and necrosis [21].p53 plays a pivotal role in determining the fate of th...

show abstract

Section: Metabolic Disordersmentioning

confidence: 99%

Role of p53 in the Regulation of Cellular Senescence

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Angiotensin-converting enzyme (ACE), KLF-4, myocardin Maegdefessel et al, 2013;Maegdefessel et al, 2015;Metzinger-Le Meuth et al, 2017;Ballantyne et al, 2019;Vacante et al, 2019 EVs induce numerous injury-associated responses in other vascular cells, leading to the development of CVDs (Carracedo et al, 2018a). MiRNAs are essential to the homeostasis and maintenance of EC activity (Ballantyne et al, 2019).…”

Section: Vsmcs Contractility and Proliferationmentioning

confidence: 99%

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

Carracedo

Alique

Vida

et al. 2020

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

Cardiovascular diseases (CVDs), especially those involving a systemic inflammatory process such as atherosclerosis, remain the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is a systemic condition affecting approximately 10% of the general population. The prevalence of CKD has increased over the past decades because of the aging of the population worldwide. Indeed, CVDs in patients with CKD constitute a premature form of CVD observed in the general population. Multiple studies indicate that patients with renal disease undergo accelerated aging, which precipitates the appearance of pathologies, including CVDs, usually associated with advanced age. In this review, we discuss several aspects that characterize CKD-associated CVDs, such as etiopathogenic elements that CKD patients share with the general population, changes in the cellular balance of reactive oxygen species (ROS), and the associated process of cellular senescence. Uremiaassociated aging is linked with numerous changes at the cellular and molecular level. These changes are similar to those observed in the normal process of physiologic aging. We also discuss new perspectives in the study of CKD-associated CVDs and epigenetic alterations in intercellular signaling, mediated by microRNAs and/or extracellular vesicles (EVs), which promote vascular damage and subsequent development of CVD. Understanding the processes and factors involved in accelerated senescence and other abnormal intercellular signaling will identify new therapeutic targets and lead to improved methods of diagnosis and monitoring for patients with CKD-associated CVDs.

show abstract

“…On the contrary, injecting senescent cells could drive age-related diseases, indicating the critical role played by these cells in determining the physical condition [ 38 ]. Senescent cells have been reported to release more EVs than normal cells, and they exhibit a totally different composition [ 39 ]. These EVs could also be considered part of the SASPs and could play role in senescent cell-induced premature aging.…”

Section: Senescence and Its Effect On Stem Cell Biology Transplanmentioning

confidence: 99%

Nano-Vesicle (Mis)Communication in Senescence-Related Pathologies

Saheera

Potnuri²,

Krishnamurthy

2020

Cells

View full text Add to dashboard Cite

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising of exosomes, apoptotic bodies, and microvesicles. Of the extracellular vesicles, exosomes are the most widely sorted and extensively explored for their contents and function. The size of the nanovesicular structures (exosomes) range from 30 to 140 nm and are present in various biological fluids such as saliva, plasma, urine etc. These cargo-laden extracellular vesicles arise from endosome-derived multivesicular bodies and are known to carry proteins and nucleic acids. Exosomes are involved in multiple physiological and pathological processes, including cellular senescence. Exosomes mediate signaling crosstalk and play a critical role in cell–cell communications. Exosomes have evolved as potential biomarkers for aging-related diseases. Aging, a physiological process, involves a progressive decline of function of organs with a loss of homeostasis and increasing probability of illness and death. The review focuses on the classic view of exosome biogenesis, biology, and age-associated changes. Owing to their ability to transport biological information among cells, the review also discusses the interplay of senescent cell-derived exosomes with the aging process, including the susceptibility of the aging population to COVID-19 infections.

show abstract

Endothelial Extracellular Vesicles Produced by Senescent Cells: Pathophysiological Role in the Cardiovascular Disease Associated with all Types of Diabetes Mellitus

Cited by 30 publications

References 98 publications

Role of p53 in the Regulation of Cellular Senescence

Role of p53 in the Regulation of Cellular Senescence

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

Nano-Vesicle (Mis)Communication in Senescence-Related Pathologies

Contact Info

Product

Resources

About