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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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Impaired vascular contractility in female Sol-Eng+ mice as compared to control mice.Maximal contraction to KCl (30 mM) (A). Maximal contraction to PGF2α (10μM) (B) and to PHE (1 μM) (C) in Sol-Eng+ and control mice. Comparison of dose-response to PGF2α (D) and PHE (E) in Sol-Eng+ as compared to control mice. Data are shown as mean ± S.E.M. Unpaired t-test, **p≤0.01, ***p≤0.001.
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pone.0119665.g007: Impaired vascular contractility in female Sol-Eng+ mice as compared to control mice.Maximal contraction to KCl (30 mM) (A). Maximal contraction to PGF2α (10μM) (B) and to PHE (1 μM) (C) in Sol-Eng+ and control mice. Comparison of dose-response to PGF2α (D) and PHE (E) in Sol-Eng+ as compared to control mice. Data are shown as mean ± S.E.M. Unpaired t-test, **p≤0.01, ***p≤0.001.

Mentions: In order to evaluate a possible impact of high soluble endoglin levels on aortic function, vascular contractility was evaluated in Sol-Eng+ and control mice. Receptor-independent vascular contraction induced by KCl (30 mM) was similar in aorta taken from each experimental group (control female, Sol-Eng+ female, control male, Sol-Eng+ male; Fig. 7A). Also, prostaglandin F2α (PGF2α)-induced vasoconstriction was not different between Sol-Eng+ and control female mice (212.3±21.06 vs. 254.2±18.22, respectively) as well as between Sol-Eng+ and control male mice (254.6±17.87 vs. 254.2±26.57, respectively) (Fig. 7B). In contrast, the vasoconstrictor response to phenylephrine (PHE) was significantly reduced in female Sol-Eng+ mice when compared to control mice (75.53±15.39 vs. 139.3±7.83, respectively), while in male Sol-Eng+ this response was not altered (123.2±18.98 vs. 132.1±15.23, respectively) (Fig. 7C). Dose-response curves for PGF2α and PHE are shown in Fig. 7D and 7E, respectively.


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)

Impaired vascular contractility in female Sol-Eng+ mice as compared to control mice.Maximal contraction to KCl (30 mM) (A). Maximal contraction to PGF2α (10μM) (B) and to PHE (1 μM) (C) in Sol-Eng+ and control mice. Comparison of dose-response to PGF2α (D) and PHE (E) in Sol-Eng+ as compared to control mice. Data are shown as mean ± S.E.M. Unpaired t-test, **p≤0.01, ***p≤0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0119665.g007: Impaired vascular contractility in female Sol-Eng+ mice as compared to control mice.Maximal contraction to KCl (30 mM) (A). Maximal contraction to PGF2α (10μM) (B) and to PHE (1 μM) (C) in Sol-Eng+ and control mice. Comparison of dose-response to PGF2α (D) and PHE (E) in Sol-Eng+ as compared to control mice. Data are shown as mean ± S.E.M. Unpaired t-test, **p≤0.01, ***p≤0.001.
Mentions: In order to evaluate a possible impact of high soluble endoglin levels on aortic function, vascular contractility was evaluated in Sol-Eng+ and control mice. Receptor-independent vascular contraction induced by KCl (30 mM) was similar in aorta taken from each experimental group (control female, Sol-Eng+ female, control male, Sol-Eng+ male; Fig. 7A). Also, prostaglandin F2α (PGF2α)-induced vasoconstriction was not different between Sol-Eng+ and control female mice (212.3±21.06 vs. 254.2±18.22, respectively) as well as between Sol-Eng+ and control male mice (254.6±17.87 vs. 254.2±26.57, respectively) (Fig. 7B). In contrast, the vasoconstrictor response to phenylephrine (PHE) was significantly reduced in female Sol-Eng+ mice when compared to control mice (75.53±15.39 vs. 139.3±7.83, respectively), while in male Sol-Eng+ this response was not altered (123.2±18.98 vs. 132.1±15.23, respectively) (Fig. 7C). Dose-response curves for PGF2α and PHE are shown in Fig. 7D and 7E, respectively.

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