Emerging roles of extracellular vesicles in cardiac repair and rejuvenation

Alibhai, Faisal J.; Tobin, Stephanie; Yeganeh, Azadeh; Weisel, Richard D.; Li, Ren‐Ke

doi:10.1152/ajpheart.00100.2018

Cited by 32 publications

(28 citation statements)

References 115 publications

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“…Extracellular vesicle (EV) is a broad term used to describe membrane encapsulated vesicles that range in size from 30 to 1,000 nm and arise from different modes of secretion. Extracellular vesicles are secreted by cell types throughout the body into the extracellular environment or bodily fluids such as the blood and urine where they carry a number of factors including microRNAs (miRNAs) and proteins (Alibhai, Tobin, Yeganeh, Weisel, & Li, ; Yanez‐Mo et al, ). Changes in plasma EV content reflect changes in cellular function in a number of disease states.…”

Section: Introductionmentioning

confidence: 99%

Cellular senescence contributes to age‐dependent changes in circulating extracellular vesicle cargo and function

et al. 2020

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Extracellular vesicles (EVs) have emerged as important regulators of inter‐cellular and inter‐organ communication, in part via the transfer of their cargo to recipient cells. Although circulating EVs have been previously studied as biomarkers of aging, how circulating EVs change with age and the underlying mechanisms that contribute to these changes are poorly understood. Here, we demonstrate that aging has a profound effect on the circulating EV pool, as evidenced by changes in concentration, size, and cargo. Aging also alters particle function; treatment of cells with EV fractions isolated from old plasma reduces macrophage responses to lipopolysaccharide, increases phagocytosis, and reduces endothelial cell responses to vascular endothelial growth factor compared to cells treated with young EV fractions. Depletion studies indicate that CD63+ particles mediate these effects. Treatment of macrophages with EV‐like particles revealed that old particles increased the expression of EV miRNAs in recipient cells. Transfection of cells with microRNA mimics recapitulated some of the effects seen with old EV‐like particles. Investigation into the underlying mechanisms using bone marrow transplant studies revealed circulating cell age does not substantially affect the expression of aging‐associated circulating EV miRNAs in old mice. Instead, we show that cellular senescence contributes to changes in particle cargo and function. Notably, senolytic treatment of old mice shifted plasma particle cargo and function toward that of a younger phenotype. Collectively, these results demonstrate that senescent cells contribute to changes in plasma EVs with age and suggest a new mechanism by which senescent cells can affect cellular functions throughout the body.

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Section: Introductionmentioning

confidence: 99%

Cellular senescence contributes to age‐dependent changes in circulating extracellular vesicle cargo and function

et al. 2020

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“…EVs are attracting considerable interest in the cardiovascular field and have been shown to play an important role in improving cardiac function and promoting recovery after ischemic insult. 61 However, one of the major challenges for the therapeutic translation of EVs is the introduction of unwanted contaminants by widely used recovery techniques. 7 Here, we demonstrated a reproducible and standardisable EV isolation technique based on SEC that allowed efficient purification of intact EVs from homogenous population of human CMs.…”

Section: Discussionmentioning

confidence: 99%

Highly purified extracellular vesicles from human cardiomyocytes demonstrate preferential uptake by human endothelial cells

et al. 2020

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“…More directed therapies may improve clinical outcomes. In addition to the secretion of cytokines and chemokines, immune cells also secrete extracellular vesicles (EVs) which can, in turn, influence cardiac viability post-MI [188]. For example, EVs isolated from M1 activated macrophages induced neonatal rat cardiomyocyte death in-vitro in an NF-κB-dependent manner, suggesting that the adverse effects of M1 cells on cardiac viability may in-part be mediated through EVs [189].…”

Section: Anti-inflammatoriesmentioning

confidence: 99%

Considering Cause and Effect of Immune Cell Aging on Cardiac Repair after Myocardial Infarction

Tobin

Alibhai

Weisel

et al. 2020

Cells

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The importance of the immune system for cardiac repair following myocardial infarction is undeniable; however, the complex nature of immune cell behavior has limited the ability to develop effective therapeutics. This limitation highlights the need for a better understanding of the function of each immune cell population during the inflammatory and resolution phases of cardiac repair. The development of reliable therapies is further complicated by aging, which is associated with a decline in cell and organ function and the onset of cardiovascular and immunological diseases. Aging of the immune system has important consequences on heart function as both chronic cardiac inflammation and an impaired immune response to cardiac injury are observed in older individuals. Several studies have suggested that rejuvenating the aged immune system may be a valid therapeutic candidate to prevent or treat heart disease. Here, we review the basic patterns of immune cell behavior after myocardial infarction and discuss the autonomous and nonautonomous manners of hematopoietic stem cell and immune cell aging. Lastly, we identify prospective therapies that may rejuvenate the aged immune system to improve heart function such as anti-inflammatory and senolytic therapies, bone marrow transplant, niche remodeling and regulation of immune cell differentiation.

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Emerging roles of extracellular vesicles in cardiac repair and rejuvenation

Cited by 32 publications

References 115 publications

Cellular senescence contributes to age‐dependent changes in circulating extracellular vesicle cargo and function

Cellular senescence contributes to age‐dependent changes in circulating extracellular vesicle cargo and function

Highly purified extracellular vesicles from human cardiomyocytes demonstrate preferential uptake by human endothelial cells

Considering Cause and Effect of Immune Cell Aging on Cardiac Repair after Myocardial Infarction

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