Chronic aerobic exercise: targeting two birds with one stone

Islam, Torikul; Hall, Shelby A; Lesniewski, Lisa A.

doi:10.1113/jp280929

Cited by 2 publications

(7 citation statements)

References 5 publications

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“…Together, impaired EDD and elevated arterial stiffness are the major components of arterial dysfunction that predict and lead to clinical CVDs (Donato et al, 2018;Islam et al, 2021;Martens & Seals, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, dysfunction in endothelial cells may result in detrimental consequences across many organs and tissues (Bloom et al., 2022 ; Donato et al., 2018 ). Age‐related endothelial dysfunction is characterized by elevated markers of cellular senescence, inflammation, and oxidative stress (Bloom et al., 2023 ; Islam et al., 2021 ). Inflammation and oxidative stress attenuate the bioavailability of nitric oxide (NO), a key endothelial‐derived vasodilatory molecule, resulting in impairments in endothelial‐dependent dilation (EDD) (Donato et al., 2018 ; Islam et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Age‐related endothelial dysfunction is characterized by elevated markers of cellular senescence, inflammation, and oxidative stress (Bloom et al., 2023 ; Islam et al., 2021 ). Inflammation and oxidative stress attenuate the bioavailability of nitric oxide (NO), a key endothelial‐derived vasodilatory molecule, resulting in impairments in endothelial‐dependent dilation (EDD) (Donato et al., 2018 ; Islam et al., 2021 ). Furthermore, endothelial‐derived inflammatory cytokines, chemokines, extracellular matrix proteins, and reactive oxygen species modulate vascular smooth cell function contributing to arterial stiffness (Donato et al., 2018 ; Martens & Seals, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, endothelial‐derived inflammatory cytokines, chemokines, extracellular matrix proteins, and reactive oxygen species modulate vascular smooth cell function contributing to arterial stiffness (Donato et al., 2018 ; Martens & Seals, 2016 ). Together, impaired EDD and elevated arterial stiffness are the major components of arterial dysfunction that predict and lead to clinical CVDs (Donato et al., 2018 ; Islam et al., 2021 ; Martens & Seals, 2016 ). Emerging evidence also suggests that the vascular endothelium is a critical regulator of systemic metabolic function (Graupera & Claret, 2018 ; Pi et al., 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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Endothelial cell‐specific reduction in mTOR ameliorates age‐related arterial and metabolic dysfunction

Islam,

Hall,

Dutson

et al. 2023

Aging Cell

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Systemic inhibition of the mammalian target of rapamycin (mTOR) delays aging and many age‐related conditions including arterial and metabolic dysfunction. However, the mechanisms and tissues involved in these beneficial effects remain largely unknown. Here, we demonstrate that activation of S6K, a downstream target of mTOR, is increased in arteries with advancing age, and that this occurs preferentially in the endothelium compared with the vascular smooth muscle. Induced endothelial cell‐specific deletion of mTOR reduced protein expression by 60–70%. Although this did not significantly alter arterial and metabolic function in young mice, endothelial mTOR reduction reversed arterial stiffening and improved endothelium‐dependent dilation (EDD) in old mice, indicating an improvement in age‐related arterial dysfunction. Improvement in arterial function in old mice was concomitant with reductions in arterial cellular senescence, inflammation, and oxidative stress. The reduction in endothelial mTOR also improved glucose tolerance in old mice, and this was associated with attenuated hepatic gluconeogenesis and improved lipid tolerance, but was independent of alterations in peripheral insulin sensitivity, pancreatic beta cell function, or fasted plasma lipids in old mice. Lastly, we found that endothelial mTOR reduction suppressed gene expression of senescence and inflammatory markers in endothelial‐rich (i.e., lung) and metabolically active organs (i.e., liver and adipose tissue), which may have contributed to the improvement in metabolic function in old mice. This is the first evidence demonstrating that reducing endothelial mTOR in old age improves arterial and metabolic function. These findings have implications for future drug development.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Endothelial cell‐specific reduction in mTOR ameliorates age‐related arterial and metabolic dysfunction

Islam,

Hall,

Dutson

et al. 2023

Aging Cell

Self Cite

View full text Add to dashboard Cite

show abstract

“…While large plaques may lead to arterial occlusion and cardiovascular events; more commonly, plaque instability leads to plaque rupture or thrombotic events leading to myocardial infarction, stroke, and the associated morbidity and mortality [ 2 ]. Although, numerous hemodynamic and circulating factors contribute to disease progression, dyslipidemia, particularly elevated blood low-density lipoprotein (LDL), is a direct cause of atherosclerosis [ 1 , 2 , 4 , 5 ]. Much of the previous efforts targeting atherosclerotic diseases were focused on lowering cholesterol, resulting in the emergence of cholesterol lowering drugs such as statins [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Heterozygosity for ADP-ribosylation factor 6 suppresses the burden and severity of atherosclerosis

Gogulamudi,

Islam,

Durrant

et al. 2023

PLoS ONE

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Atherosclerosis is the root cause of major cardiovascular diseases (CVD) such as myocardial infarction and stroke. ADP-ribosylation factor 6 (Arf6) is a ubiquitously expressed GTPase known to be involved in inflammation, vascular permeability and is sensitive to changes in shear stress. Here, using atheroprone, ApoE-/- mice, with a single allele deletion of Arf6 (HET) or wildtype Arf6 (WT), we demonstrate that reduction in Arf6 attenuates atherosclerotic plaque burden and severity. We found that plaque burden in the descending aorta was lower in HET compared to WT mice (p˂0.001) after the consumption of an atherogenic Paigen diet for 5 weeks. Likewise, luminal occlusion, necrotic core size, plaque grade, elastic lamina breaks, and matrix deposition were lower in the aortic root atheromas of HET compared to WT mice (all p≤0.05). We also induced advanced human-like complex atherosclerotic plaque in the left carotid artery using partial carotid ligation surgery and found that atheroma area, plaque grade, intimal necrosis, intraplaque hemorrhage, thrombosis, and calcification were lower in HET compared to WT mice (all p≤0.04). Our findings suggest that the atheroprotection afforded by Arf6 heterozygosity may result from reduced immune cell migration (all p≤0.005) as well as endothelial and vascular smooth muscle cell proliferation (both p≤0.001) but independent of changes in circulating lipids (all p≥0.40). These findings demonstrate a critical role for Arf6 in the development and severity of atherosclerosis and suggest that Arf6 inhibition can be explored as a novel therapeutic strategy for the treatment of atherosclerotic CVD.

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Chronic aerobic exercise: targeting two birds with one stone

Cited by 2 publications

References 5 publications

Endothelial cell‐specific reduction in mTOR ameliorates age‐related arterial and metabolic dysfunction

Endothelial cell‐specific reduction in mTOR ameliorates age‐related arterial and metabolic dysfunction

Heterozygosity for ADP-ribosylation factor 6 suppresses the burden and severity of atherosclerosis

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