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High soluble endoglin levels do not induce endothelial dysfunction in mouse aorta.

Nemeckova I, Serwadczak A, Oujo B, Jezkova K, Rathouska J, Fikrova P, Varejckova M, Bernabeu C, Lopez-Novoa JM, Chlopicki S, Nachtigal P - PLoS ONE (2015)

Bottom Line: Increased levels of a soluble form of endoglin (sEng) circulating in plasma have been detected in various pathological conditions related to cardiovascular system.As expected, male and female Sol-Eng+ transgenic mice showed higher levels of plasma concentrations of human sEng as well as increased blood arterial pressure, as compared to control animals.However, these data do not rule out the possibility that soluble endoglin might contribute to alteration of endothelial function in combination with other risk factors related to cardiovascular disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove, 500 05, Czech Republic.

ABSTRACT
Increased levels of a soluble form of endoglin (sEng) circulating in plasma have been detected in various pathological conditions related to cardiovascular system. High concentration of sEng was also proposed to contribute to the development of endothelial dysfunction, but there is no direct evidence to support this hypothesis. Therefore, in the present work we analyzed whether high sEng levels induce endothelial dysfunction in aorta by using transgenic mice with high expression of human sEng. Transgenic mice with high expression of human sEng on CBAxC57Bl/6J background (Sol-Eng+) and age-matched transgenic littermates that do not develop high levels of human soluble endoglin (control animals in this study) on chow diet were used. As expected, male and female Sol-Eng+ transgenic mice showed higher levels of plasma concentrations of human sEng as well as increased blood arterial pressure, as compared to control animals. Functional analysis either in vivo or ex vivo in isolated aorta demonstrated that the endothelium-dependent vascular function was similar in Sol-Eng+ and control mice. In addition, Western blot analysis showed no differences between Sol-Eng+ and control mice in the protein expression levels of endoglin, endothelial NO-synthase (eNOS) and pro-inflammatory ICAM-1 and VCAM-1 from aorta. Our results demonstrate that high levels of soluble endoglin alone do not induce endothelial dysfunction in Sol-Eng+ mice. However, these data do not rule out the possibility that soluble endoglin might contribute to alteration of endothelial function in combination with other risk factors related to cardiovascular disorders.

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Related in: MedlinePlus

Endothelium-dependent responses in Sol-Eng+ and control mice.Acetylcholine-induced relaxation in PHE or PGF2α (1 μM) pre-constricted vessels (A). Effect of L-NAME on the PHE (1 μM)-induced contraction (B). Data are shown as mean ± S.E.M. Mann-Whitney test, unpaired t-test, *p≤0.05, ***p≤0.001.
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pone.0119665.g005: Endothelium-dependent responses in Sol-Eng+ and control mice.Acetylcholine-induced relaxation in PHE or PGF2α (1 μM) pre-constricted vessels (A). Effect of L-NAME on the PHE (1 μM)-induced contraction (B). Data are shown as mean ± S.E.M. Mann-Whitney test, unpaired t-test, *p≤0.05, ***p≤0.001.

Mentions: Endothelium-dependent vasodilation induced by acetylcholine (Ach) in PHE or PGF2α (1 μM) pre-contracted aorta was similar in Sol-Eng+ and control female mice and also in Sol-Eng+ and control male animals (81.18±3.26 vs. 73.65±2.46, 85.01±3.13 vs. 78.9±6.26, respectively) (Fig. 5A). The effect of L-NAME on PHE-induced constriction was also similar in all experimental groups (females from Sol-Eng+ Δ = 92.17 and control mice Δ = 102.7; males from Sol-Eng+ Δ = 97.8 and control mice Δ = 124.5) (Fig. 5B).


High soluble endoglin levels do not induce endothelial dysfunction in mouse aorta.

Nemeckova I, Serwadczak A, Oujo B, Jezkova K, Rathouska J, Fikrova P, Varejckova M, Bernabeu C, Lopez-Novoa JM, Chlopicki S, Nachtigal P - PLoS ONE (2015)

Endothelium-dependent responses in Sol-Eng+ and control mice.Acetylcholine-induced relaxation in PHE or PGF2α (1 μM) pre-constricted vessels (A). Effect of L-NAME on the PHE (1 μM)-induced contraction (B). Data are shown as mean ± S.E.M. Mann-Whitney test, unpaired t-test, *p≤0.05, ***p≤0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359129&req=5

pone.0119665.g005: Endothelium-dependent responses in Sol-Eng+ and control mice.Acetylcholine-induced relaxation in PHE or PGF2α (1 μM) pre-constricted vessels (A). Effect of L-NAME on the PHE (1 μM)-induced contraction (B). Data are shown as mean ± S.E.M. Mann-Whitney test, unpaired t-test, *p≤0.05, ***p≤0.001.
Mentions: Endothelium-dependent vasodilation induced by acetylcholine (Ach) in PHE or PGF2α (1 μM) pre-contracted aorta was similar in Sol-Eng+ and control female mice and also in Sol-Eng+ and control male animals (81.18±3.26 vs. 73.65±2.46, 85.01±3.13 vs. 78.9±6.26, respectively) (Fig. 5A). The effect of L-NAME on PHE-induced constriction was also similar in all experimental groups (females from Sol-Eng+ Δ = 92.17 and control mice Δ = 102.7; males from Sol-Eng+ Δ = 97.8 and control mice Δ = 124.5) (Fig. 5B).

Bottom Line: Increased levels of a soluble form of endoglin (sEng) circulating in plasma have been detected in various pathological conditions related to cardiovascular system.As expected, male and female Sol-Eng+ transgenic mice showed higher levels of plasma concentrations of human sEng as well as increased blood arterial pressure, as compared to control animals.However, these data do not rule out the possibility that soluble endoglin might contribute to alteration of endothelial function in combination with other risk factors related to cardiovascular disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove, 500 05, Czech Republic.

ABSTRACT
Increased levels of a soluble form of endoglin (sEng) circulating in plasma have been detected in various pathological conditions related to cardiovascular system. High concentration of sEng was also proposed to contribute to the development of endothelial dysfunction, but there is no direct evidence to support this hypothesis. Therefore, in the present work we analyzed whether high sEng levels induce endothelial dysfunction in aorta by using transgenic mice with high expression of human sEng. Transgenic mice with high expression of human sEng on CBAxC57Bl/6J background (Sol-Eng+) and age-matched transgenic littermates that do not develop high levels of human soluble endoglin (control animals in this study) on chow diet were used. As expected, male and female Sol-Eng+ transgenic mice showed higher levels of plasma concentrations of human sEng as well as increased blood arterial pressure, as compared to control animals. Functional analysis either in vivo or ex vivo in isolated aorta demonstrated that the endothelium-dependent vascular function was similar in Sol-Eng+ and control mice. In addition, Western blot analysis showed no differences between Sol-Eng+ and control mice in the protein expression levels of endoglin, endothelial NO-synthase (eNOS) and pro-inflammatory ICAM-1 and VCAM-1 from aorta. Our results demonstrate that high levels of soluble endoglin alone do not induce endothelial dysfunction in Sol-Eng+ mice. However, these data do not rule out the possibility that soluble endoglin might contribute to alteration of endothelial function in combination with other risk factors related to cardiovascular disorders.

Show MeSH
Related in: MedlinePlus