Reduction of Nitric Oxide Producing Activity Associated with in Vitro Aging in Cultured Human Umbilical Vein Endothelial Cell

Sato, Ikuko; Morita, Ikuo; Kaji, Koichi; Ikeda, Masa Aki; Nagao, Masanori; Murota, Sei‐itsu

doi:10.1006/bbrc.1993.2153

Cited by 116 publications

(63 citation statements)

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“…In aging and in replicative senescence, nitric oxide (NO) levels tend to deteriorate, 42 and NO is an important factor in preventing or delaying the onset of endothelial senescence. 43,44 We therefore also considered the role of NO.…”

Section: Discussionmentioning

confidence: 99%

Glucagon-Like Peptide 1 Prevents Reactive Oxygen Species–Induced Endothelial Cell Senescence Through the Activation of Protein Kinase A

Oeseburg

Boer²,

Buikema

et al. 2010

ATVB

219

175

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Objective-Endothelial cell senescence is an important contributor to vascular aging and is increased under diabetic conditions. Here we investigated whether the antidiabetic hormone glucagon-like peptide 1 (GLP-1) could prevent oxidative stress-induced cellular senescence in endothelial cells. Methods and Results-In Zucker diabetic fatty rats, a significant 2-fold higher level of vascular senescence was observed compared with control lean rats. Dipeptidyl-peptidase 4 (DPP-4) inhibition significantly increased GLP-1 levels in these animals and reduced senescence almost to lean animal levels. In vitro studies with human umbilical vein endothelial cells showed that GLP-1 had a direct protective effect on oxidative stress (H 2 O 2 )-induced senescence and was able to attenuate oxidative stress-induced DNA damage and cellular senescence. The GLP-1 analogue exendin-4 provided similar results, whereas exendin fragment 9 -39, a GLP-1 receptor antagonist, abolished this effect. Intracellular signaling by the phosphoinositide 3-kinase (PI3K)/Akt survival pathway did not appear to be involved. Further analysis revealed that GLP-1 activates the cAMP response element-binding (CREB) transcription factor in a cAMP/protein kinase A (PKA)-dependent manner, and inhibition of the cAMP/PKA pathway abolished the GLP-1 protective effect. Expression analysis revealed that GLP-1 can induce the oxidative defense genes HO-1 and NQO1. Conclusion-Dipeptidyl-peptidase 4 inhibition protects against vascular senescence in a diabetic rat model. In vitro studies with human umbilical vein endothelial cells showed that reactive oxygen species-induced senescence was attenuated by GLP-1 in a receptor-dependent manner involving downstream PKA signaling and induction of antioxidant genes.

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Section: Discussionmentioning

confidence: 99%

Glucagon-Like Peptide 1 Prevents Reactive Oxygen Species–Induced Endothelial Cell Senescence Through the Activation of Protein Kinase A

Oeseburg

Boer²,

Buikema

et al. 2010

ATVB

219

175

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“…127,128 Decreases in both NO production and eNOS activity in human umbilical vein endothelial cells and human aortic endothelial cells (HAECs) are associated with aging. 129,130 Matsushita et al 130 demonstrated that shear stress-induced increase in NO production was diminished in senescent HAECs and that stable expression of TERT restored the decreased eNOS expression and NO production associated with aging. Minamino et al 131 reported that HAECs from human atherosclerotic lesions presented phenotypes of senescent cells and decreases in eNOS expression and eNOS activity.…”

Section: Endothelial Cell Senescencementioning

confidence: 99%

Endothelial dysfunction and hypertension in aging

2012

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Hypertension is one of the common diseases in the elderly. The prevalence of hypertension markedly increases with advancing age. Both aging and hypertension have a critical role in cardiovascular and cerebrovascular complications. Although aging and hypertension, either independently or collectively, impair endothelial function, aging and hypertension may have similar cascades for the pathogenesis and development of endothelial dysfunction. Nitric oxide (NO) has an important role in regulation of vascular tone. Decrease in NO bioavailability by endothelial dysfunction would lead to elevation of blood pressure. An imbalance of reduced production of NO or increased production of reactive oxygen species, mainly superoxide, may promote endothelial dysfunction. One possible mechanism by which the prevalence of hypertension is increased in relation to aging may be advancing endothelial dysfunction associated with aging through an increase in oxidative stress. In addition, endothelial cell senescence is also involved in aging-related endothelial dysfunction. In this review, we focus on recent findings and interactions between endothelial function, oxidative stress and hypertension in aging.

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“…Senescent ECs show attenuated endothelial NO production 144 and increased endothelin-1 release. 145 Latepassage ECs also show reduced expression of the adhesion molecules VCAM-1 and intracellular adhesion molecule-1 (ICAM-1), increased activation of nuclear factor (NF)-B, and increased susceptibility to apoptosis.…”

Section: Endothelial Cellsmentioning

confidence: 99%

Aging and Atherosclerosis

Wang

Bennett

2012

Circulation Research

721

323

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Atherosclerosis is classed as a disease of aging, such that increasing age is an independent risk factor for the development of atherosclerosis. Atherosclerosis is also associated with premature biological aging, as atherosclerotic plaques show evidence of cellular senescence characterized by reduced cell proliferation, irreversible growth arrest and apoptosis, elevated DNA damage, epigenetic modifications, and telomere shortening and dysfunction. Not only is cellular senescence associated with atherosclerosis, there is growing evidence that cellular senescence promotes atherosclerosis. This review examines the pathology of normal vascular aging, the evidence for cellular senescence in atherosclerosis, the mechanisms underlying cellular senescence including reactive oxygen species, replication exhaustion and DNA damage, the functional consequences of vascular cell senescence, and the possibility that preventing accelerated cellular senescence is a therapeutic target in atherosclerosis.

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Reduction of Nitric Oxide Producing Activity Associated with in Vitro Aging in Cultured Human Umbilical Vein Endothelial Cell

Cited by 116 publications

References 0 publications

Glucagon-Like Peptide 1 Prevents Reactive Oxygen Species–Induced Endothelial Cell Senescence Through the Activation of Protein Kinase A

Glucagon-Like Peptide 1 Prevents Reactive Oxygen Species–Induced Endothelial Cell Senescence Through the Activation of Protein Kinase A

Endothelial dysfunction and hypertension in aging

Aging and Atherosclerosis

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