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Nitric Oxide Increases Arterial Endotheial Permeability through Mediating VE-Cadherin Expression during Arteriogenesis.

Yang B, Cai B, Deng P, Wu X, Guan Y, Zhang B, Cai W, Schaper J, Schaper W - PLoS ONE (2015)

Bottom Line: Induced iNOS was found mainly in smooth muscle cells, but also in other vascular cells and macrophages; 2) in NAV VE-cadherin was strongly expressed in EC.In CVs, VE-cadherin was significantly downregulated, with a discontinuous and punctate pattern.In conclusion, our data for the first time reveal the expression profile of VE-cadherin and alterations of vascular permeability in CVs, suggesting that NO-mediated VE-cadherin pathway may be one important mechanism responsible, at least in part, for macrophage invasion during arteriogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Histology & Embryology, School of Basic Medicine, Central South Univ., Changsha, 410078, Hunan, P.R. China; Department of Anatomy, School of Basic Medicine, Nanchang Univ., Nanchang, 330006, Jiangxi, P.R. China.

ABSTRACT
Macrophage invasion is an important event during arteriogenesis, but the underlying mechanism is still only partially understood. The present study tested the hypothesis that nitric oxide (NO) and VE-cadherin, two key mediators for vascular permeability, contribute to this event in a rat ischemic hindlimb model. In addition, the effect of NO on expression of VE-caherin and endothelial permeability was also studied in cultured HUVECs. We found that: 1) in normal arteriolar vessels (NAV), eNOS was moderately expressed in endothelial cells (EC) and iNOS was rarely detected. In contrast, in collateral vessels (CVs) induced by simple femoral artery ligation, both eNOS and iNOS were significantly upregulated (P<0.05). Induced iNOS was found mainly in smooth muscle cells, but also in other vascular cells and macrophages; 2) in NAV VE-cadherin was strongly expressed in EC. In CVs, VE-cadherin was significantly downregulated, with a discontinuous and punctate pattern. Administration of nitric oxide donor DETA NONOate (NONOate) further reduced the amounts of Ve-cadherin in CVs, whereas NO synthase inhibitor L-NAME inhibited downregulation of VE-cadherin in CVs; 3) in normal rats Evans blue extravasation (EBE) was low in the musculus gracilis, FITC-dextron leakage was not detected in the vascular wall and few macrophages were observed in perivascular space. In contrast, EBE was significantly increased in femoral artery ligation rats, FITC-dextron leakage and increased amounts of macrophages were detected in CVs, which were further enhanced by administration of NONOate, but inhibited by L-NAME supplement; 4) in vitro experiments confirmed that an increase in NO production reduced VE-cadherin expression, correlated with increases in the permeability of HUVECs. In conclusion, our data for the first time reveal the expression profile of VE-cadherin and alterations of vascular permeability in CVs, suggesting that NO-mediated VE-cadherin pathway may be one important mechanism responsible, at least in part, for macrophage invasion during arteriogenesis.

No MeSH data available.


Related in: MedlinePlus

Quantitative analysis of fluorescence density (AU/μm2) of FITC-dextran in the collaterals and capilaries of the musculus gracilis from sham, femoral artery ligation (FAL), NONOate treated (FAL + NONOate) and L-NAME treated (FAL + L-NAME) groups.*P < 0.05 vs sham., #P < 0.05 vs FAL.
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pone.0127931.g005: Quantitative analysis of fluorescence density (AU/μm2) of FITC-dextran in the collaterals and capilaries of the musculus gracilis from sham, femoral artery ligation (FAL), NONOate treated (FAL + NONOate) and L-NAME treated (FAL + L-NAME) groups.*P < 0.05 vs sham., #P < 0.05 vs FAL.

Mentions: In sham rats, VE-cadherin was strongly expressed in EC, the staining between EC was continuous, whereas in FAL rats, VE-cadherin staining was present as discontinuous and punctate pattern (Fig 2A and 2B). Quantitative analysis of fluorescence density showed that VE-cadherin protein was significantly reduced in FAL rats (P<0.05), 1.58 fold lower than that in sham rats (Fig 3A). In the permeability test, FITC-dextran was rarely detected in the vascular wall and was very low in the musculus gracilis in sham rats (Fig 4A and 4E and Fig 5). In contrast, in FAL rats, FITC-dextran was present in the vascular wall and FITC-dextran leakage in the musculus gracilis was significantly increased (Fig 4B and 4F and Fig 5). Similar to FITC-dextran examination, Evans blue extravasation (EBE) was significantly increased in the musculus gracilis in the FAL rats than that in sham rats (Fig 6). Correlated with the changes in FITC-dextran/ EBE leakage, few macrophages were detected in sham rats, but significantly increased (P<0.05) in FAL rats (Fig 2E and 2F and Fig 3B).


Nitric Oxide Increases Arterial Endotheial Permeability through Mediating VE-Cadherin Expression during Arteriogenesis.

Yang B, Cai B, Deng P, Wu X, Guan Y, Zhang B, Cai W, Schaper J, Schaper W - PLoS ONE (2015)

Quantitative analysis of fluorescence density (AU/μm2) of FITC-dextran in the collaterals and capilaries of the musculus gracilis from sham, femoral artery ligation (FAL), NONOate treated (FAL + NONOate) and L-NAME treated (FAL + L-NAME) groups.*P < 0.05 vs sham., #P < 0.05 vs FAL.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4489889&req=5

pone.0127931.g005: Quantitative analysis of fluorescence density (AU/μm2) of FITC-dextran in the collaterals and capilaries of the musculus gracilis from sham, femoral artery ligation (FAL), NONOate treated (FAL + NONOate) and L-NAME treated (FAL + L-NAME) groups.*P < 0.05 vs sham., #P < 0.05 vs FAL.
Mentions: In sham rats, VE-cadherin was strongly expressed in EC, the staining between EC was continuous, whereas in FAL rats, VE-cadherin staining was present as discontinuous and punctate pattern (Fig 2A and 2B). Quantitative analysis of fluorescence density showed that VE-cadherin protein was significantly reduced in FAL rats (P<0.05), 1.58 fold lower than that in sham rats (Fig 3A). In the permeability test, FITC-dextran was rarely detected in the vascular wall and was very low in the musculus gracilis in sham rats (Fig 4A and 4E and Fig 5). In contrast, in FAL rats, FITC-dextran was present in the vascular wall and FITC-dextran leakage in the musculus gracilis was significantly increased (Fig 4B and 4F and Fig 5). Similar to FITC-dextran examination, Evans blue extravasation (EBE) was significantly increased in the musculus gracilis in the FAL rats than that in sham rats (Fig 6). Correlated with the changes in FITC-dextran/ EBE leakage, few macrophages were detected in sham rats, but significantly increased (P<0.05) in FAL rats (Fig 2E and 2F and Fig 3B).

Bottom Line: Induced iNOS was found mainly in smooth muscle cells, but also in other vascular cells and macrophages; 2) in NAV VE-cadherin was strongly expressed in EC.In CVs, VE-cadherin was significantly downregulated, with a discontinuous and punctate pattern.In conclusion, our data for the first time reveal the expression profile of VE-cadherin and alterations of vascular permeability in CVs, suggesting that NO-mediated VE-cadherin pathway may be one important mechanism responsible, at least in part, for macrophage invasion during arteriogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Histology & Embryology, School of Basic Medicine, Central South Univ., Changsha, 410078, Hunan, P.R. China; Department of Anatomy, School of Basic Medicine, Nanchang Univ., Nanchang, 330006, Jiangxi, P.R. China.

ABSTRACT
Macrophage invasion is an important event during arteriogenesis, but the underlying mechanism is still only partially understood. The present study tested the hypothesis that nitric oxide (NO) and VE-cadherin, two key mediators for vascular permeability, contribute to this event in a rat ischemic hindlimb model. In addition, the effect of NO on expression of VE-caherin and endothelial permeability was also studied in cultured HUVECs. We found that: 1) in normal arteriolar vessels (NAV), eNOS was moderately expressed in endothelial cells (EC) and iNOS was rarely detected. In contrast, in collateral vessels (CVs) induced by simple femoral artery ligation, both eNOS and iNOS were significantly upregulated (P<0.05). Induced iNOS was found mainly in smooth muscle cells, but also in other vascular cells and macrophages; 2) in NAV VE-cadherin was strongly expressed in EC. In CVs, VE-cadherin was significantly downregulated, with a discontinuous and punctate pattern. Administration of nitric oxide donor DETA NONOate (NONOate) further reduced the amounts of Ve-cadherin in CVs, whereas NO synthase inhibitor L-NAME inhibited downregulation of VE-cadherin in CVs; 3) in normal rats Evans blue extravasation (EBE) was low in the musculus gracilis, FITC-dextron leakage was not detected in the vascular wall and few macrophages were observed in perivascular space. In contrast, EBE was significantly increased in femoral artery ligation rats, FITC-dextron leakage and increased amounts of macrophages were detected in CVs, which were further enhanced by administration of NONOate, but inhibited by L-NAME supplement; 4) in vitro experiments confirmed that an increase in NO production reduced VE-cadherin expression, correlated with increases in the permeability of HUVECs. In conclusion, our data for the first time reveal the expression profile of VE-cadherin and alterations of vascular permeability in CVs, suggesting that NO-mediated VE-cadherin pathway may be one important mechanism responsible, at least in part, for macrophage invasion during arteriogenesis.

No MeSH data available.


Related in: MedlinePlus