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Endothelial dysfunction of resistance vessels in female apolipoprotein E-deficient mice
Maine S Cola1, Agata L Gava, Silvana S Meyrelles
1Laboratory of Transgenes and Cardiovascular Control, Physiological Sciences Graduate Program, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, Brazil.
Insights
Hypercholesterolemia impairs endothelial function in female mice, even after ovariectomy. Atherosclerotic ApoE-deficient mice show reduced vasodilation compared to normal C57BL/6 mice.
Area of Science:
- Cardiovascular biology
- Endocrinology
- Vascular physiology
Background:
- Hypercholesterolemia's impact on vasomotricity in apolipoprotein E-deficient (ApoE) mice is not fully understood.
- Previous studies focused on conductance vessels in male mice on high-fat diets.
- This study investigates endothelial function in resistance vessels of female mice.
Purpose of the Study:
- To evaluate endothelial function in resistance vessels of normal C57BL/6 (C57) and hypercholesterolemic (ApoE) female mice.
- To assess the effects of ovariectomy on endothelial function in these groups.
- To compare vascular reactivity to vasoactive agents.
Main Methods:
- Twenty-week-old C57 and ApoE female mice underwent ovariectomy or sham surgery.
- Vascular reactivity to norepinephrine, acetylcholine (ACh), and sodium nitroprusside (SNP) was assessed 30 days post-surgery.
- Dose-response curves were generated in isolated mesenteric arteriolar beds.
Main Results:
- ACh-induced relaxation was significantly reduced in ApoE mice compared to C57 mice.
- Ovariectomy impaired ACh-induced relaxation in C57 mice but not ApoE mice.
- SNP-induced vasorelaxation and NE-induced vasoconstriction were similar between ApoE and C57 groups.
Conclusions:
- Endothelial function is impaired in the resistance vessels of spontaneously atherosclerotic ApoE-deficient female mice.
- Endothelial dysfunction in hypercholesterolemic mice was severe enough that ovariectomy did not cause further vascular damage.
- These findings highlight sex-specific and atherosclerosis-related vascular changes.
Background:
The effects of hypercholesterolemia on vasomotricity in apolipoprotein E-deficient (ApoE) mice, a murine model of spontaneous atherosclerosis, are still unclear. The studies were mostly performed in conductance vessels from male mice fed a high-fat diet. In the present study, we evaluated the endothelial function of resistance vessels from normal C57BL/6 (C57) and hypercholesterolemic (ApoE) female mice in both normal and ovariectomized conditions.
Methods:
Twenty week-old C57 and ApoE mice underwent ovariectomy or sham surgery and were studied 30 days later. The vascular reactivities to norepinephrine (NE, 10(-9) to 2 x 10(-3) mol/L), acetylcholine (ACh) and sodium nitroprusside (SNP) (10(-10) to 10(-3) mol/L) were evaluated in the isolated mesenteric arteriolar bed through dose-response curves.
Results:
ACh-induced relaxation was significantly reduced (P < 0.05) in ApoE compared with C57 animals, as indicated by both the maximal response (37 +/- 4% vs. 72 +/- 1%) and the LogEC50 (-5.67 +/- 0.18 vs. -6.23 +/- 0.09 mol/L). Ovariectomy caused a significant impairment in ACh-induced relaxation in the C57 group (maximal response: 61 +/- 4%) but did not worsen the deficient state of relaxation in ApoE animals (maximal response: 39 +/- 5%). SNP-induced vasorelaxation and NE-induced vasoconstriction were similar in ApoE and C57 female mice.
Conclusion:
These data show an impairment of endothelial function in the resistance vessels of spontaneously atherosclerotic (ApoE-deficient) female mice compared with normal (C57) female mice. The endothelial dysfunction in hypercholesterolemic animals was so marked that ovariectomy, which impaired endothelial function in C57 mice, did not cause additional vascular damage in ApoE-deficient mice.
