Endothelial nitric oxide synthase induces heat shock protein HSPA6 (HSP70B′) in human arterial smooth muscle cells

McCullagh, Karl J. A.; Cooney, Ronan; O’Brien, Timothy

doi:10.1016/j.niox.2015.11.002

Cited by 18 publications

(13 citation statements)

References 44 publications

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“…NO is an important neurotransmitter secreted by vascular endothelial cells and has numerous functions, including inhibiting monocyte-macrophage and platelet adhesion, decreasing the monolayer permeability of vascular endothelial cells and reducing vascular endothelial cell and smooth muscle cell proliferation (33). A total of 30% NO in the blood is derived from endothelial nitric oxide synthase genes expressed by vascular endothelial cells (34). The present study detected NO level and NOS activity under high glucose conditions.…”

Section: Discussionmentioning

confidence: 50%

Effects of reduced β2 glycoprotein I on high glucose-induced cell death in HUVECs

Zhang

et al. 2017

Molecular Medicine Reports

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Reduced β2 glycoprotein I (β2GPI) has been demonstrated to exhibit a beneficial effect in diabetic atherosclerosis and retinal neovascularization. However, the effect of reduced β2GPI on vascular disorders in diabetic mellitus (DM) remains to be elucidated. The present study established a high glucose‑induced injury model using human umbilical cords veins (HUVECs) and evaluated the protective effects of reduced β2GPI against the injury. The data demonstrated that a low concentration of reduced β2GPI (0.5 µM) mitigated high glucose‑induced cell loss, decreased nitric oxide (NO) production and resulted in calcium overloading. Mechanically, reduced β2GPI additionally reversed high glucose‑induced phosphatase and tensin homolog (PTEN) accumulation, decrease of protein kinase B phosphorylation and nitric oxide synthase activity, and increase of cyclooxygenase‑2 activity. It was further confirmed that PTEN inhibitor‑bpV (1 µM) exhibited similar effects to those resulting from reduced β2GPI. Overall, the data revealed that reduced β2GPI exerts protective effects from glucose‑induced injury in HUVECs, potentially via decreasing PTEN levels. The present study suggests reduced β2GPI may act as a novel therapeutic strategy for the treatment of vascular disorders in DM.

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Section: Discussionmentioning

confidence: 50%

Effects of reduced β2 glycoprotein I on high glucose-induced cell death in HUVECs

Zhang

et al. 2017

Molecular Medicine Reports

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“…G894T polymorphism results in reduced eNOS enzymatic activity and decreased production of NO by endothelial cells [ 30 ]. Reduced eNOS activity causes an increase in smooth muscle cell proliferation after vascular injury, and inhibition of the endothelial NO pathway are present in atherosclerosis [ 31 – 32 ]. Zhang et al reported eNOS G894T polymorphism may play an important role in CAD development among Asia population [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

An association between the endothelial nitric oxide synthase gene G894T polymorphism and premature coronary artery disease: a meta-analysis

Zhu

Gong

et al. 2017

Oncotarget

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Previous epidemiological studies have suggested that genetic factors are more likely to influence the development of premature coronary artery disease (CAD) than disease in older patients. Several studies have evaluated the association between the G894T polymorphism located in an exon of endothelial nitric oxide synthase (eNOS) and the risk of premature CAD. However, the findings were inconsistent. Thus, we performed a meta-analysis to clarify the association; we conducted both overall and subgroup analyses. Odds ratios and 95% confidence interval were calculated to evaluate the association between the G894T polymorphism and the risk of premature CAD. Overall analysis revealed a significant association. Subgroup analysis in terms of ethnicity revealed a significant association, in all models evaluated, between the G894T polymorphism and susceptibility to premature CAD in mixed population. In contrast, no such association was evident in Caucasians and Asians. On further subgroup analysis based on the premature CAD subtypes, we found that the G894T polymorphism was correlated with premature myocardial infarction (MI) but not with premature CAD without MI. In conclusion, we confirmed that the eNOS G894T polymorphism is a risk factor for premature CAD, particularly in those suffering premature MI.

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“…Noticeably, a cluster of heat shock protein member A (HSP70) gene family members including HSPA1A (also named HSP70A), HSPA1B (also named HSP70B), HSPA5 and HSPA8 was amongst the genes up-regulated, which were associated with endothelial function (Fig. 5E ) 27 , 28 . Moreover, we identified growth arrest and DNA-damage-inducible protein (GADD45) genes including GADD45A, GADD45B and GADD45G were also significantly up-regulated, which have been implicated in stress signaling to activate several stress response kinase such as P38 MAPK, thus resulting in apoptosis (Fig.…”

Section: Resultsmentioning

confidence: 99%

Modeling cadmium-induced endothelial toxicity using human pluripotent stem cell-derived endothelial cells

Tang

Liang

2017

Sci Rep

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Cadmium (Cd) is a harmful heavy metal that results in vascular diseases such as atherosclerosis. Prior evidence revealed that Cd induced endothelial cell (EC) death and dysfunction, supporting that ECs are a primary target of Cd-induced toxicity, and can cause severe pathologies of vascular diseases. However, the underlying mechanisms remain unclear. In this study, we investigated the mechanisms of Cd-induced endothelial toxicity in a human model system of H9 human pluripotent stem cell-derived endothelial cells (H9-ECs). We showed that H9-ECs were susceptible to CdCl2 induction, leading to detrimental changes of cell structure and significantly elevated level of apoptosis. We demonstrated that CdCl2-treated H9-ECs gave rise to a clear EC dysfunction phenotype and significantly differential transcriptomic profile. Signaling pathway analysis revealed that P38 or ERK signaling pathway is critical to cadmium-induced EC apoptosis and dysfunction, and inhibition of P38 or ERK effectively rescued CdCl2-induced endothelial toxicity in H9-ECs. Conclusively, hPSC-ECs can be a reliable model to recapitulate the EC pathological features and transcriptomic profile, which may provide a unique platform for understanding the cellular and molecular mechanisms of Cd-induced endothelial toxicity and for identifying therapeutic drugs for Cd-induced vascular diseases.

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Endothelial nitric oxide synthase induces heat shock protein HSPA6 (HSP70B′) in human arterial smooth muscle cells

Cited by 18 publications

References 44 publications

Effects of reduced β2 glycoprotein I on high glucose-induced cell death in HUVECs

Effects of reduced β2 glycoprotein I on high glucose-induced cell death in HUVECs

An association between the endothelial nitric oxide synthase gene G894T polymorphism and premature coronary artery disease: a meta-analysis

Modeling cadmium-induced endothelial toxicity using human pluripotent stem cell-derived endothelial cells

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