Limits...
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.

Show MeSH

Related in: MedlinePlus

Pressure responses to agonists or antagonists of the NO-cGMP-system in Sol-Eng+ and control mice.Maximal hypotensive effect of sodium nitroprusside (SNP; 2 mg/Kg b.w.) in Sol-Eng+ and control mice (A). Maximal hypertensive effect of L-NAME (50 mg/Kg b.w.) in Sol-Eng+ and control mice (B). Effects were measured by telemetry. SABP: Systolic blood arterial pressure. Data are shown as mean ± S.E.M. ANOVA and unpaired t-test with respect to control, *p≤0.05; ANOVA and paired t-test with respect to basal conditions, #p≤0.05.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4359129&req=5

pone.0119665.g003: Pressure responses to agonists or antagonists of the NO-cGMP-system in Sol-Eng+ and control mice.Maximal hypotensive effect of sodium nitroprusside (SNP; 2 mg/Kg b.w.) in Sol-Eng+ and control mice (A). Maximal hypertensive effect of L-NAME (50 mg/Kg b.w.) in Sol-Eng+ and control mice (B). Effects were measured by telemetry. SABP: Systolic blood arterial pressure. Data are shown as mean ± S.E.M. ANOVA and unpaired t-test with respect to control, *p≤0.05; ANOVA and paired t-test with respect to basal conditions, #p≤0.05.

Mentions: To test the NO-dependent function in vivo, we determined the response of BP to the blockade of nitric oxide (NO) synthesis and nitrite concentration in the urine. Acute administration of the NOS inhibitor L-NAME induced a sustained and similar hypertensive response in both groups of animals (Fig. 3B). Furthermore, acute administration of Ach seems to induce a similar drop of BP in Sol-Eng+ mice and control animals (data not shown). However, it should be noted that the effect of acetylcholine with this experimental design was very variable, probably explained because it is very short and in many cases the hypotensive effect was artifacted by the removal of the mice from their cages to inject the drug and the consequent effects on arterial pressure, thus making difficult to correctly assess the hypotensive effect of ACh. Acute administration of sodium nitroprusside (SNP) also induced a significantly fall of BP in Sol-Eng+ and control mice (Fig. 3A), with no significant differences between both groups of mice. Urinary excretion of nitrites, a stable-end product of NO metabolism, was also not statistically different in Sol-Eng+vs. control mice (Fig. 4).


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)

Pressure responses to agonists or antagonists of the NO-cGMP-system in Sol-Eng+ and control mice.Maximal hypotensive effect of sodium nitroprusside (SNP; 2 mg/Kg b.w.) in Sol-Eng+ and control mice (A). Maximal hypertensive effect of L-NAME (50 mg/Kg b.w.) in Sol-Eng+ and control mice (B). Effects were measured by telemetry. SABP: Systolic blood arterial pressure. Data are shown as mean ± S.E.M. ANOVA and unpaired t-test with respect to control, *p≤0.05; ANOVA and paired t-test with respect to basal conditions, #p≤0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0119665.g003: Pressure responses to agonists or antagonists of the NO-cGMP-system in Sol-Eng+ and control mice.Maximal hypotensive effect of sodium nitroprusside (SNP; 2 mg/Kg b.w.) in Sol-Eng+ and control mice (A). Maximal hypertensive effect of L-NAME (50 mg/Kg b.w.) in Sol-Eng+ and control mice (B). Effects were measured by telemetry. SABP: Systolic blood arterial pressure. Data are shown as mean ± S.E.M. ANOVA and unpaired t-test with respect to control, *p≤0.05; ANOVA and paired t-test with respect to basal conditions, #p≤0.05.
Mentions: To test the NO-dependent function in vivo, we determined the response of BP to the blockade of nitric oxide (NO) synthesis and nitrite concentration in the urine. Acute administration of the NOS inhibitor L-NAME induced a sustained and similar hypertensive response in both groups of animals (Fig. 3B). Furthermore, acute administration of Ach seems to induce a similar drop of BP in Sol-Eng+ mice and control animals (data not shown). However, it should be noted that the effect of acetylcholine with this experimental design was very variable, probably explained because it is very short and in many cases the hypotensive effect was artifacted by the removal of the mice from their cages to inject the drug and the consequent effects on arterial pressure, thus making difficult to correctly assess the hypotensive effect of ACh. Acute administration of sodium nitroprusside (SNP) also induced a significantly fall of BP in Sol-Eng+ and control mice (Fig. 3A), with no significant differences between both groups of mice. Urinary excretion of nitrites, a stable-end product of NO metabolism, was also not statistically different in Sol-Eng+vs. control mice (Fig. 4).

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