Nitric oxide protects endothelium from cadmium mediated leakiness

Nagarajan, Sankari; Rajendran, Saranya; Saran, Uttara; Priya, Mani Krishna; Swaminathan, Akila; Siamwala, Jamila H.; Sinha, Swaraj; Veeriah, Vimal; Sonar, Punam; Jadhav, Vivek; Ali, B. M. Jaffar; Chatterjee, Suvro

doi:10.1002/cbin.10070

Cited by 20 publications

(20 citation statements)

References 53 publications

(88 reference statements)

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“…Results also demonstrated that sFRP4 decreased NO production in EC irrespective of cell origin (micro-vs. macro-vascular EC) and that this inhibition remained effective up to 24 h post treatment. Our data parallels previous studies that have similarly shown altered endothelial actin cytoskeleton and increased vascular permeability following inhibition of NO synthesis [26,27,35].…”

Section: Discussionsupporting

confidence: 92%

“…DAF-FM was performed on EAhy926 cells treated with sFRP4 (250 pg/ml), Bradykinin (BK; 5 μM), SP (10 μM), 8-Br (50 μM), CAT (30 U), MnTBAP (10 μM) and their combinations with sFRP4 for 4 h as per the protocol described elsewhere [26]. L-Arg was used as positive control.…”

Section: Daf-fm Fluorimetric Assaymentioning

confidence: 99%

“…Fertilized four day incubated eggs were obtained from Poultry Research Station, Potheri, Chennai. Texas red permeability assays were performed on CAM treated with control (1X PBS), sFRP4 , SP and sFRP4 + SP for 4 h as per protocol described elsewhere [26].…”

Section: Texas Red Permeability Assay In Chorionic-allantoic Membranementioning

confidence: 99%

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sFRP4 signalling of apoptosis and angiostasis uses nitric oxide-cGMP-permeability axis of endothelium

et al. 2017

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Nitric oxide (NO) plays a critical role in endothelial functions such as cellular migration, vascular permeability and angiogenesis. Angiogenesis, the formation of new blood vessels from "pre-existing" ones is a carefully regulated process and essential during reproduction, development and wound healing. Previously our lab group reported that Secreted Frizzled-Related Protein 4 (sFRP4) could inhibit angiogenesis in both in vitro and in vivo conditions. sFRP4 belongs to a family of secreted glycoproteins that function as antagonists of the canonical Wnt signalling pathway. Although the pro-apoptotic role of sFRP4 is well discussed in literature, little is known in regards to its anti-angiogenic property. The objective of this study was to elucidate sFRP4 implications in NO biology of the endothelium. Results demonstrate that sFRP4 causes endothelial dysfunction by suppressing NO-cGMP signaling and elevating corresponding ROS levels. The imbalance between NO and ROS levels results in apoptosis and subsequent leakiness of endothelium as confirmed in vivo (Texas red/Annxin - CAM assay) and in vitro (Monolayer permeability assay) conditions. Furthermore utilizing peptides synthesized from the CRD domain of sFRP4, our results showed that while these peptides were able to cause endothelial dysfunctions, they did not cause apoptosis of the endothelial cells. Thereby confirming that sFRP4 can mediate its anti-angiogenic effect independent of its pro-apoptotic property. In conclusion, the current study reports that sFRP4-mediated anti-angiogenesis occurs as a result of impaired NO-cGMP signaling which in turn allow for elevation of redox levels and promotion of apoptosis of endothelial cells.

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Section: Discussionsupporting

confidence: 92%

Section: Daf-fm Fluorimetric Assaymentioning

confidence: 99%

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sFRP4 signalling of apoptosis and angiostasis uses nitric oxide-cGMP-permeability axis of endothelium

et al. 2017

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“…The HUVECs were then incubated with EHNs (5 μg mL −1 ), catalase (1200 units per mL) and MnTBAP (10 μM) for 4 h. Subsequently the media were replaced with 5 µM DAF-FM and incubated in the dark for 30 min at room temperature. The DAF-FM solution from each of the treatments was transferred to a 96 well microtitre plate and the fluorescence was measured using a fluorescence spectrophotometer 22,23 with λ ex : 495 nm and λ em : 515 nm.…”

Section: Methodsmentioning

confidence: 99%

Investigation of molecular mechanisms and regulatory pathways of pro-angiogenic nanorods

et al. 2015

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Angiogenesis, a process involving the growth of new blood vessels from the pre-existing vasculature, plays a crucial role in various pathophysiological conditions. We have previously demonstrated that europium hydroxide [EuIII(OH)3] nanorods (EHNs) exhibit pro-angiogenic properties through the generation of reactive oxygen species (ROS) and mitogen activated protein kinase (MAPK) activation. Considering the enormous implication of angiogenesis in cardiovascular diseases (CVDs) and cancer, it is essential to understand in-depth molecular mechanisms and signaling pathways in order to develop the most efficient and effective alternative treatment strategy for CVDs. However, the exact underlying mechanism and cascade signaling pathways behind the pro-angiogenic properties exhibited by EHNs still remain unclear. Herein, we report for the first time that the hydrogen peroxide (H2O2), a redox signaling molecule, generated by these EHNs activates the endothelial nitric oxide synthase (eNOS) that promotes the nitric oxide (NO) production in a PI3K (phosphoinositide 3-kinase)/Akt dependent manner, eventually triggering angiogenesis. We intensely believe that the investigation and understanding of the in-depth molecular mechanism and signaling pathways of EHNs induced angiogenesis will help us in developing an effective alternative treatment strategy for cardiovascular related and ischemic diseases where angiogenesis plays an important role.

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“…Increasing reports have reviewed the importance of the integrity of endothelial structure for viable vascular function (Kolluru et al 2006;Messner et al 2009;Knoflach et al 2011;Oliveira et al 2011). Additionally, there is a growing volume of evidence implicating the endothelium as a primary target of Cd toxicity (Prozialeck et al 2008;Nagarajan et al 2013). The components of the medial layer of the aorta-the smooth muscle cell (SMC) and connective tissue like elastin and collagen-contribute to the elasticity of the aorta (Shirwany and Zou 2010).…”

Section: Discussionmentioning

confidence: 99%

Cadmium-induced endothelial dysfunction mediated by asymmetric dimethylarginine

Al‐Naemi

Das

2020

Environ Sci Pollut Res

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Cadmium (Cd) is a naturally occurring toxic heavy metal with no known essential biological functions. Exposure to Cd increases the risk of cardiovascular disease by disrupting vascular homeostasis at the endothelium. The aim of the study was to evaluate the effect of chronic low-dose Cd on vascular structure and function. Fifty adult male Sprague Dawley rats were grouped and assigned to one of two treatments for 14 weeks. The control group received normal water for 14 weeks while the Cd-treated group received 15 mg Cd/kg B.W. as CdCl 2 in water for 10 weeks. A subset of the Cd-treated group received 15 mg Cd/kg B.W. as CdCl 2 in water for 10 weeks followed by 4 weeks of normal water. Results show an overall decline in vascular function and structure. Withdrawal of Cd treatment showed a considerable restoration of vascular structure and vasorelaxation function. Additionally, asymmetric dimethylarginine (ADMA) bioavailability was found to be lowered over time. Interestingly, the expression of eNOS in the Cd-treated group was found to be significantly elevated during the exposure by more than 3-fold in comparison with that in the control group. This protein expression was similar to the control group after the withdrawal of Cd treatment. Taken together, the results suggest that ADMA, an eNOS inhibitor, may play a role in altering endothelial function in the presence of cadmium. In conclusion, the findings indicate that even at low doses, Cd leads to endothelial dysfunction mediated by ADMA.

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Nitric oxide protects endothelium from cadmium mediated leakiness

Cited by 20 publications

References 53 publications

sFRP4 signalling of apoptosis and angiostasis uses nitric oxide-cGMP-permeability axis of endothelium

sFRP4 signalling of apoptosis and angiostasis uses nitric oxide-cGMP-permeability axis of endothelium

Investigation of molecular mechanisms and regulatory pathways of pro-angiogenic nanorods

Cadmium-induced endothelial dysfunction mediated by asymmetric dimethylarginine

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