Hydrogen-rich saline attenuates vascular smooth muscle cell proliferation and neointimal hyperplasia by inhibiting reactive oxygen species production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways

Chen, Yali; Jiang, Jinyao; Miao, Huibing; Chen, Xingjuan; Sun, Xuejun; Li, Yongjun

doi:10.3892/ijmm.2013.1256

Cited by 32 publications

(41 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Excessive ROS production by infiltrating leukocytes in the vascular wall contributes to SMC proliferation and arterial stenosis [34,38] and therapeutic attempts to scavenge excess ROS or interrupt ROS production have proven efficacious in preclinical models of neointima formation [39]. Superoxide production in leukocytes is largely mediated via NADPH oxidase 2 (NOX2), which is activated, in part, by the Ras-dependent kinases Erk and Akt [17,28,40].…”

Section: Resultsmentioning

confidence: 99%

Neurofibromin is a novel regulator of Ras-induced reactive oxygen species production in mice and humans

Bessler

Hudson

Zhang

et al. 2016

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Neurofibromatosis type 1 (NF1) predisposes individuals to early and debilitating cardiovascular disease. Loss of function mutations in the NF1 tumor suppressor gene, which encodes the protein neurofibromin, leads to accelerated p21Ras activity and phosphorylation of multiple downstream kinases, including Erk and Akt. Nf1 heterozygous (Nf1+/−) mice develop a robust neointima that mimics human disease. Monocytes/macrophages play a central role in NF1 arterial stenosis as Nf1 mutations in myeloid cells alone are sufficient to reproduce the enhanced neointima observed in Nf1+/− mice. Though the molecular mechanisms underlying NF1 arterial stenosis remain elusive, macrophages are important producers of reactive oxygen species (ROS) and Ras activity directly regulates ROS production. Here, we use compound mutant and lineage-restricted mice to demonstrate that Nf1+/− macrophages produce excessive ROS, which enhance Nf1+/− smooth muscle cell proliferation in vitro and in vivo. Further, use of a specific NADPH oxidase-2 inhibitor to limit ROS production prevents neointima formation in Nf1+/− mice. Finally, mononuclear cells from asymptomatic NF1 patients have increased oxidative DNA damage, an indicator of chronic exposure to oxidative stress. These data provide genetic and pharmacologic evidence that excessive exposure to oxidant species underlie NF1 arterial stenosis and provide a platform for designing novels therapies and interventions.

show abstract

Section: Resultsmentioning

confidence: 99%

Neurofibromin is a novel regulator of Ras-induced reactive oxygen species production in mice and humans

Bessler

Hudson

Zhang

et al. 2016

Free Radical Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…It has also been shown that molecular hydrogen is able to inhibit the TNF-α/NFκβ pathway as well as the Ras-ERK1/2-MEK1/2 and Akt pathways, these findings as well as possible gene regulatory effects are illustrated in Figure 3[15,16]. The suppression of these pathways by use of hydrogen was demonstrated in neointimal hyperplasia models in rats.…”

Section: Mechanismsmentioning

confidence: 95%

The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance

2013

View full text Add to dashboard Cite

Studies on molecular hydrogen have evolved tremendously from its humble beginnings and have continued to change throughout the years. Hydrogen is extremely unique since it has the capability to act at the cellular level. Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell. Hydrogen is most commonly applied as a gas, water, saline, and can be applied in a variety of other mediums. There are also few side effects involving hydrogen, thus making hydrogen a perfect medical gas candidate for the convention of novel therapeutic strategies against cardiovascular, cerebrovascular, cancer, metabolic, and respiratory diseases and disorders. Although hydrogen appears to be faultless at times, there still are several deficiencies or snares that need to be investigated by future studies. This review article seeks to delve and comprehensively analyze the research and experiments that alludes to molecular hydrogen being a novel therapeutic treatment that medicine desperately needs.

show abstract

“…Numerous studies have consistently shown that the contributors were significantly down regulated after applying hydrogen medicine therapy [10, 14,26,27,41]. Besides, with the deepening biological mechanism of hydrogen research being developed, scientists gradually found that hydrogen therapy can significantly suppress many pathological signal transduction channels such as NF-κβ, MAPK, Lyn-P, and MEK-1 as well as ERK1/2 pathways and ultimately achieve the goal of recovery from many diseases [44,45,[49][50][51][52][53]. In addition, it is worth noting that as H2 is moderate enough, it can selectively react with only hydroxyl radicals (•OH) and peroxynitrite(ONOO-), the main contributors of oxidative stress in vitro and in vivo without disturbing metabolic redox reactions …”

Section: Hypothesismentioning

confidence: 99%

Hydrogen Medicine Therapy: An Effective and Promising Novel Treatment for Multiple Organ Dysfunction Syndrome (MODS) Induced by Influenza and Other Viral Infections Diseases?

Hu¹

2017

SOJMID

View full text Add to dashboard Cite

Hydrogen, a non-cytotoxic molecule, is one of nature's most simple elements [1,2]. Recent studies revealed that intraperitoneal injection of hydrogen-rich saline has surprising anti-inflammation, anti-oxidant, anti-apoptosis effects and protected organism against polymicrobial sepsis injury, acute peritonitis injury both by reducing oxidative stress and via decreasing mass proinflammatory responses. It is also well known that the majority of viral -induced tissue damage and discomfort are mainly caused by an inflammatory cytokine storm and oxidative stress rather than by virus itself [3][4][5]. Studies have shown that suppressing the cytokine storm and reducing oxidative stress can significantly alleviate the symptoms of influenza and other severe viral infections diseases [3][4][5][6][7]. However, none of the studies have been focused on the solution as an anti-virus infection therapy yet. Therefore, we hypothesize that hydrogen-rich solution therapy may be a safe, reliable, and effective treatment for Multiple Organ Dysfunction Syndrome (MODS) induced by influenza and other viral infectious diseases.

show abstract

Hydrogen-rich saline attenuates vascular smooth muscle cell proliferation and neointimal hyperplasia by inhibiting reactive oxygen species production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways

Cited by 32 publications

References 57 publications

Neurofibromin is a novel regulator of Ras-induced reactive oxygen species production in mice and humans

Neurofibromin is a novel regulator of Ras-induced reactive oxygen species production in mice and humans

The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance

Hydrogen Medicine Therapy: An Effective and Promising Novel Treatment for Multiple Organ Dysfunction Syndrome (MODS) Induced by Influenza and Other Viral Infections Diseases?

Contact Info

Product

Resources

About