NecroX-5 exerts anti-inflammatory and anti-fibrotic effects via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway in hypoxia/reoxygenation-treated rat hearts

Thu, Vũ Thị; Kim, Hyoung Kyu; Long, Lê Thanh; Thuy, To Thanh; Huy, Nguyễn Quang; Kim, Soon Ha; Kim, Nari; Ko, Kyung Soo; Rhee, Byoung Doo; Han, Jin

doi:10.4196/kjpp.2016.20.3.305

Cited by 16 publications

(19 citation statements)

References 67 publications

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“…The SNPs in certain genes, for example, IRS1 , endothelin receptor type A ( EDNRA ), DCN , and ZFHX3 , are frequently associated with CVD or related traits, including our study. Insulin signaling and function was shown to reduce atherosclerosis through the endothelin receptors, whereas downregulation of DCN and ZFHX3 were associated with anti‐inflammatory/antiapoptotic and perturbed Ca2 + homeostasis, respectively . Functional studies are available for a few but future research is needed to ascertain the separate or combined effects of these genes that have been consistently associated with CVEs.…”

Section: Discussionmentioning

confidence: 99%

Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study

Shendre

Irvin

Wiener

et al. 2017

JAHA

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BackgroundLocal ancestry in relation to clinical cardiovascular events (CVEs) among African Americans can provide insight into their genetic susceptibility to the disease.Methods and ResultsWe examined local European ancestry (LEA) association with CVEs among 3000 African Americans from the Atherosclerosis Risk in Communities Study (ARIC). We estimated LEA using Local Ancestry Inference in adMixed Populations using Linkage Disequilibrium (LAMP‐LD) and examined its association with myocardial infarction, stroke, coronary heart disease and its composite and cardiovascular disease composite using logistic regression. Genome‐wide significance was achieved by 121 LEA regions in relation to myocardial infarction and 2 in relation to the cardiovascular disease composite. The LEA region downstream of 4q32.1 was significantly associated with 2 times higher odds of myocardial infarction (P=1.45×10−6). The LEA region upstream of 6q11.1 was associated with 0.37 times lower odds of fatal coronary heart disease (P=7.34×10−4), whereas the LEA region downstream of 21q21.1 was associated with 1.55 times higher odds of composite coronary heart disease (P=3.45×10−4). Association of LEA with stroke was observed in the region upstream of 6p22.3 with a 1.57 times higher odds of stroke (P=9.69×10−4). Likewise, the LEA region on 4q32.3 was associated with a 1.53 times higher odds of composite cardiovascular disease (P=3.04×10−4). We also found 20 of the LEA regions at previously significant cardiovascular disease single‐nucleotide polymorphisms to be associated with CVE in our study.ConclusionsFuture studies are needed to replicate and/or determine the causal variants driving our associations and explore clinical applications for those consistently associated with CVEs.

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Section: Discussionmentioning

confidence: 99%

Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study

Shendre

Irvin

Wiener

et al. 2017

JAHA

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“…Moreover, antioxidants and anti-inflammatory agents have been applied to suppress the cellular effects of ischemia [20]. Recently, anti-necrotic effects of NecroX-5 on IRI have been evaluated in the murine heart and canine liver IRI models [8]. NecroX-5 strongly prevented myocardial damage in ischemic heart disorders by preventing mitochondrial dysfunction [8].…”

Section: Discussionmentioning

confidence: 99%

“…Significant improvement in the protection of cell and tissue has been showed against various injury factors, such as neomycin, nitroprusside, oxidative stress, and gentamicin [5][6][7]. Recently, the fundamental role of NecroX-5 in IRI in the heart and liver has been described, however, there has been no research to determine the molecular mechanisms underlying the inhibition of NecroX-5 in IRI [8,9]. The goal of this research was to investigate the therapeutic efficiency and its underlying mechanism of NecroX-5 on the IRI in rat flap model.…”

Section: Original Articlementioning

confidence: 99%

The Protective Effect of NecroX-5 on Flap Survival and Ischemic Reperfusion Injury Inflammation in Rat Model

Nam

Shin

Jeong

et al. 2018

J Wound Management Res

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Background: NecroX-5 has been evaluated to have anti-necrotic potential on ischemia reperfusion injury (IRI) in skin flaps. Nevertheless, there is no study focusing on the underlying mechanism involved in this protective effect. We used NecroX-5 to assess the preventive effect and regulatory mechanisms on flap survival in rat model. Methods: Twenty male Sprague-Dawley rats were allocated into two groups with 10 each: control IRI group and IRI with 30 mg/kg of NecroX-5-treated group. On postoperative day 7, viable area of the skin flap was measured and specimens were used for immunohistochemical analysis. Results: The necrotic area of NecroX-5 group was significantly lower than those of control group (NecroX-5 group: 6 ± 0.019%; control group: 38 ± 0.11%; P < 0.05). Furthermore, levels of interleukin-1β and tumor necrosis factor-α were markedly lower in NecroX-5 groups than in control groups and NecroX-5 groups resulted in an apparent decrease of infiltrating immune cells. Conclusion: We suggest that NecroX-5 acts as a protective factor during IRI of skin flaps by inducing a negligible amount of proinflammatory cytokines.

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“…TGFβ1 is of great significance in various pathological processes, including infarction, myocardial remodeling and interstitial fibrosis (30). An analysis of TGFβ1 and SMAD2 levels and their correlation with CHD risk factors indicated that TGFβ1 is associated with the expression of lipoprotein A and uric acid (31,32). Increased levels of lipoprotein A and uric acid are considered as markers of atherosclerosis, which indicates that TGFβ1 may regulate atherosclerosis, thereby accelerating the establishment of CHD.…”

Section: Discussionmentioning

confidence: 99%

Rutin inhibits coronary heart disease through ERK1/2 and Akt signaling in a porcine model

Yao

Zhao

et al. 2017

Exp Ther Med

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Abstract.Rutin has a variety of pharmacological actions, including radical reactivity, and protective activity against lipid peroxidation, viruses and acute pancreatitis; thus, it may be used as a treatment for many diseases. The present study aimed to investigate whether rutin inhibits coronary heart disease through extracellular signal-regulated kinase (ERK) 1/2 and Akt signaling in a porcine model. Male Chinese miniature pigs were randomly divided into four groups: A sham group, a coronary heart disease (CHD) model group, a group receiving 15 mg/kg rutin for 8 weeks following CHD modeling and a group receiving 45 mg/kg rutin for 8 weeks following CHD modeling. The results suggested that treatment with rutin suppressed the reduction in left ventricular ejection fraction and increase in systolic internal diameter that occurred in CHD model pigs. Rutin administration reduced the infarct size of the myocardium, attenuated LVEF, increased LVID and inhibited urine protein concentration, BUN and Scr expression levels in CHD model pigs. Results from western blot analysis demonstrated that in CHD pigs treated with 45 mg/kg rutin, the CHD-associated increases in transforming growth factor β1 and SMAD2 expression and reductions in phosphorylated (p)-ERK1/2 and p-Akt expression were attenuated. The present study suggests that rutin inhibits coronary heart disease through ERK1/2 and Akt signaling pathways in a porcine model.

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NecroX-5 exerts anti-inflammatory and anti-fibrotic effects via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway in hypoxia/reoxygenation-treated rat hearts

Cited by 16 publications

References 67 publications

Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study

Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study

The Protective Effect of NecroX-5 on Flap Survival and Ischemic Reperfusion Injury Inflammation in Rat Model

Rutin inhibits coronary heart disease through ERK1/2 and Akt signaling in a porcine model

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