Vasculoprotective Effects of Anti-Tumor Necrosis Factor-α Treatment in Aging

Csiszár, Anna; Labinskyy, Nazar; Smith, Kira; Rivera, Aracelie; Orosz, Zsuzsanna; Ungvári, Zoltán

doi:10.2353/ajpath.2007.060708

Cited by 192 publications

(192 citation statements)

References 45 publications

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“…(56,57) Moreover, patients who have metabolic diseases such as diabetes and chronic cardiac disease also show high TNF-a levels in the blood serum. (58)(59)(60) Although the TNF-a level itself in this animal study might not be able to extrapolate to the human subject, bone formation and osteogenesis would be decreased in such patients because of the continuously high TNF-a level. In the future, targeting of TNF-a inhibition might be a useful therapeutic strategy to accelerate bone formation/osteogenesis in such patients.…”

Section: Discussionmentioning

confidence: 90%

LPS-Induced Inhibition of Osteogenesis Is TNF-α Dependent in a Murine Tooth Extraction Model

Tomomatsu

Aoki

Alles

et al. 2009

Journal of Bone and Mineral Research

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TNF-a is a major etiologic factor of inflammatory bone diseases such as periodontitis and rheumatoid arthritis. In addition, patients with metabolic diseases such as chronic heart disease and diabetes have significantly increased plasma levels of TNF-a. Several lines of evidence show inhibition of osteoblastogenesis by TNF-a in vitro. Therefore, bone formation and osteogenesis in these patients might be inhibited because of TNF-a. However, little is known about the inhibitory role of TNF-a in bone formation/ osteogenesis in vivo. The purpose of this study was to investigate the role of TNF-a in osteogenesis using a murine tooth extraction model. Lipopolysaccharide (LPS) was injected subcutaneously into the calvariae of either wildtype (WT) or TNF-a-deficient (KO) mice. The left incisor was extracted 4 days after LPS injection. The measuring area was established as the tooth socket under the mesial root of the first molar. A significant increase in serum TNF-a levels after LPS injection was observed in WT mice. The BMD of the tooth socket was significantly decreased by LPS injection 21 days after extraction in WT but not in KO mice. Histomorphometric analysis showed a significant decrease in the mineral apposition rate after LPS injection, which appeared at an early stage in WT but not in KO mice. Injection of a peptide that blocked the TNF-a signaling pathway by preventing transmission of the NF-kB signal recovered the inhibition of osteogenesis observed after LPS injection. In conclusion, TNF-a might play a major role in LPS-induced inhibition of osteogenesis under inflammatory conditions.

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Section: Discussionmentioning

confidence: 90%

LPS-Induced Inhibition of Osteogenesis Is TNF-α Dependent in a Murine Tooth Extraction Model

Tomomatsu

Aoki

Alles

et al. 2009

Journal of Bone and Mineral Research

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“…The goal should therefore be to prevent the ceramide cascade by decreasing the exposure of the endothelium to inflammatory cytokines. Several authors have been able to show reductions in TNF-α during ischemia with several different drugs including benazapril and amlodipine [36][37][38][39]. Furthermore, myocardial injury was actually shown to be smaller when there had been significant reductions in TNF-α [36].…”

Section: Tumor Necrosis Factor-α and Ceramidementioning

confidence: 99%

Ceramide: A common pathway for atherosclerosis?

et al. 2008

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Plasma sphingomyelin concentration is correlated with the development of atherosclerosis. It has been found to exist in significantly higher concentrations in aortic plaque. This appears to have clinical relevance as well as it has been shown to be an independent predictor of coronary artery disease. Ceramide, the backbone of sphingolipids, is the key component which affects atherosclerotic changes through its important second-messenger role. This paper sheds light on some of the current literature supporting the significance of ceramide with respect to its interactions with lipids, inflammatory cytokines, homocysteine and matrix metalloproteinases. Furthermore, the potential therapeutic implications of modulating ceramide concentrations are also discussed.

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“…One source of increased reactive oxygen species within arteries with age is NADPH oxidase (Csiszar et al 2007b;Durrant et al 2009;Rippe et al 2010). Cerebral arteries have greater NADPH oxidase activity compared with conduit arteries and this contributes to their greater production of superoxide (Miller et al 2005(Miller et al , 2009.…”

Section: Nadph Oxidasementioning

confidence: 99%

Beneficial effects of lifelong caloric restriction on endothelial function are greater in conduit arteries compared to cerebral resistance arteries

Walker

Henson

Reihl

et al. 2013

AGE

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Endothelial dysfunction occurs in conduit and cerebral resistance arteries with advancing age. Lifelong caloric restriction (CR) can prevent the onset of age-related dysfunction in many tissues, but its effects on cerebral resistance artery function, as compared with conduit artery function, have not been determined. We measured endothelium-dependent dilation (EDD) in the carotid artery and middle cerebral artery (MCA) from young (5-7 months), old ad libitum fed (AL, 29-32 months), and old lifelong CR (CR, 40 % CR, 29-32 months) B6D2F1 mice. Compared with young, EDD for old AL was 24 % lower in the carotid and 47 % lower in the MCA (p<0.05). For old CR, EDD was not different from young in the carotid artery (p>0.05), but was 25 % lower than young in the MCA (p<0.05). EDD was not different between groups after NO synthase inhibition with N ω -nitro-L-arginine methyl ester in the carotid artery or MCA. Superoxide production by the carotid artery and MCA was greater in old AL compared with young and old CR (p<0.05). In the carotid, incubation with the superoxide scavenger TEMPOL improved EDD for old AL (p>0.05), with no effect in young or old CR (p>0.05). In the MCA, incubation with TEMPOL or the NADPH oxidase inhibitor apocynin augmented EDD in old AL (p<0.05), but reduced EDD in young and old CR (p<0.05). Thus, age-related endothelial dysfunction is prevented by lifelong CR completely in conduit arteries, but only partially in cerebral resistance arteries. These benefits of lifelong CR on EDD result from lower oxidative stress and greater NO bioavailability.

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Vasculoprotective Effects of Anti-Tumor Necrosis Factor-α Treatment in Aging

Cited by 192 publications

References 45 publications

LPS-Induced Inhibition of Osteogenesis Is TNF-α Dependent in a Murine Tooth Extraction Model

LPS-Induced Inhibition of Osteogenesis Is TNF-α Dependent in a Murine Tooth Extraction Model

Ceramide: A common pathway for atherosclerosis?

Beneficial effects of lifelong caloric restriction on endothelial function are greater in conduit arteries compared to cerebral resistance arteries

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