Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises

Lakatta, Edward G.; Levy, Daniel

doi:10.1161/01.cir.0000048892.83521.58

Cited by 2,228 publications

(2,208 citation statements)

References 61 publications

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“…Endothelial dysfunction is the major antecedent to atherosclerosis, a predictor of clinical CVD risk, and is linked to many common disorders of aging including cognitive impairments, Alzheimer's disease, motor dysfunction, insulin resistance, and sarcopenia (Heitzer et al ., 2001; Gokce et al ., 2002; Lakatta & Levy, 2003; Widlansky et al ., 2003; Seals et al ., 2011, 2014). We have previously demonstrated that arterial SIRT1 activity is reduced with aging and contributes to the age‐related impairment in endothelial function (Donato et al ., 2011; Gano et al ., 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in developed nations (Mortality & Causes of Death, 2014), and advancing age is the primary risk factor for CVD (Lakatta & Levy, 2003). The number of older adults in the developed world is expected to at least double by 2050 (Petsko, 2008), and this is associated with projections of marked increases in CVD burden (Heidenreich et al ., 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Two key antecedents and independent predictors of clinical CVD in older adults are vascular endothelial dysfunction, assessed by endothelium‐dependent dilation (EDD), and large elastic artery stiffness, measured by aortic pulse wave velocity (aPWV) (Lakatta & Levy, 2003; Deanfield et al ., 2007; Yeboah et al ., 2007; Mitchell et al ., 2010). A common mechanism that contributes to both vascular endothelial dysfunction and large elastic artery stiffness with aging is excessive superoxide‐associated vascular oxidative stress (Seals et al ., 2011; Fleenor et al ., 2012a; Bachschmid et al ., 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Increased vascular production of superoxide occurs with aging and reduces the bioavailability of the vasoprotective and vasodilatory molecule nitric oxide (NO), while also causing alterations in major structural proteins (collagen and elastin) in the large elastic arteries (i.e., the aorta and carotid arteries) (Deanfield et al ., 2007; Fleenor et al ., 2010; Seals et al ., 2014). These changes contribute directly to age‐related endothelial dysfunction and increased arterial stiffness (Lakatta & Levy, 2003; Seals et al ., 2011). As such, treatments that reduce the excessive superoxide production in aging arteries hold the potential for improving age‐associated vascular dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

et al. 2016

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SummaryWe tested the hypothesis that supplementation of nicotinamide mononucleotide (NMN), a key NAD + intermediate, increases arterial SIRT1 activity and reverses age‐associated arterial dysfunction and oxidative stress. Old control mice (OC) had impaired carotid artery endothelium‐dependent dilation (EDD) (60 ± 5% vs. 84 ± 2%), a measure of endothelial function, and nitric oxide (NO)‐mediated EDD (37 ± 4% vs. 66 ± 6%), compared with young mice (YC). This age‐associated impairment in EDD was restored in OC by the superoxide (O2−) scavenger TEMPOL (82 ± 7%). OC also had increased aortic pulse wave velocity (aPWV, 464 ± 31 cm s−1 vs. 337 ± 3 cm s−1) and elastic modulus (EM, 6407 ± 876 kPa vs. 3119 ± 471 kPa), measures of large elastic artery stiffness, compared with YC. OC had greater aortic O2− production (2.0 ± 0.1 vs. 1.0 ± 0.1 AU), nitrotyrosine abundance (a marker of oxidative stress), and collagen‐I, and reduced elastin and vascular SIRT1 activity, measured by the acetylation status of the p65 subunit of NFκB, compared with YC. Supplementation with NMN in old mice restored EDD (86 ± 2%) and NO‐mediated EDD (61 ± 5%), reduced aPWV (359 ± 14 cm s−1) and EM (3694 ± 315 kPa), normalized O2− production (0.9 ± 0.1 AU), decreased nitrotyrosine, reversed collagen‐I, increased elastin, and restored vascular SIRT1 activity. Acute NMN incubation in isolated aortas increased NAD + threefold and manganese superoxide dismutase (MnSOD) by 50%. NMN supplementation may represent a novel therapy to restore SIRT1 activity and reverse age‐related arterial dysfunction by decreasing oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

et al. 2016

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“…Aging of endothelial cells (ECs) alters their structure and/or function, and is a critical event resulting in deterioration of vascular integrity (Tian & Li, 2014). Indeed, vascular aging is an independent risk factor of cardiovascular diseases that impair vascular health (Lakatta & Levy, 2003) and is now recognized as a target for intervention to achieve a healthier old age (Wang & Bennett, 2012). For that reason, understanding of the significance of age‐associated changes in the vascular endothelium is essential for the development of a therapeutic strategy to maintain vascular integrity (Brunner et al ., 2005).…”

Section: Introductionmentioning

confidence: 99%

Age‐associated downregulation of vasohibin‐1 in vascular endothelial cells

2016

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SummaryVasohibin‐1 (VASH1) is an angiogenesis‐inhibiting factor synthesized by endothelial cells (ECs) and it also functions to increase stress tolerance of ECs, which function is critical for the maintenance of vascular integrity. Here, we examined whether the expression of VASH1 would be affected by aging. We passaged human umbilical vein endothelial cells (HUVECs) and observed that VASH1 was downregulated in old HUVECs. This decrease in VASH1 expression with aging was confirmed in mice. To explore the mechanism of this downregulation, we compared the expression of microRNAs between old and young HUVECs by performing microarray analysis. Among the top 20 microRNAs that were expressed at a higher level in old HUVECs, the third highest microRNA, namely miR‐22‐3p, had its binding site on the 3′ UTR of VASH1 mRNA. Experiments with microRNA mimic and anti‐miR revealed that miR‐22‐3p was involved at least in part in the downregulation of VASH1 in ECs during replicative senescence. We then clarified the significance of this defective expression of VASH1 in the vasculature. When a cuff was placed around the femoral arteries of wild‐type mice and VASH1‐null mice, neointimal formation was augmented in the VASH1‐null mice accompanied by an increase in adventitial angiogenesis, macrophage accumulation in the adventitia, and medial/neointimal proliferating cells. These results indicate that in replicative senescence, the downregulation of VASH1 expression in ECs was caused, at least in part, by the alteration of microRNA expression. Such downregulation of VASH1 might be involved in the acceleration of age‐associated vascular diseases.

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APOE ε4 Genotype and Longitudinal Changes in Cerebral Blood Flow in Normal Aging

Thambisetty¹,

Beason‐Held²,

An³

et al. 2010

Arch Neurol

187

162

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Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises

Cited by 2,228 publications

References 61 publications

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

Age‐associated downregulation of vasohibin‐1 in vascular endothelial cells

APOE ε4 Genotype and Longitudinal Changes in Cerebral Blood Flow in Normal Aging

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