Impact of estrogens on atherosclerosis and bone in the apolipoprotein E-deficient mouse model.

Abstract

OBJECTIVE:

The common inflammatory pathophysiology has nourished the hypothesis of a relationship between osteoporosis and cardiovascular disease. Estrogens are key agents in the modulation of both processes. We investigated whether induction of atherosclerosis affects bone and whether estrogens modulate both processes.

METHODS:

Female apolipoprotein E-deficient mice (a well-established model of atherogenesis) were ovariectomized or falsely operated and fed either standard diet or high-fat diet (HFD). Six animals were included in each of the four groups. To clarify mechanisms, we treated preosteoblastic MC3T3-E1 cells with mouse serum.

RESULTS:

Physiological levels of estrogens in falsely operated mice limited atherosclerotic burden in the thoracic aorta, but not in the aortic arch. Bone resorption, as assessed by C-telopeptides, was increased by ovariectomy in animals fed standard diet, but not in animals fed HFD. Bone microstructural properties at the distal femur showed deteriorated trabecular architecture in bone volumetric fraction and trabecular number after ovariectomy, but trabecular pattern factor, trabecular thickness, trabecular spacing, or the structural model index remained unchanged. Changes in cortical parameters were not significant. Volumetric bone mineral density was reduced in trabecular bone, but not in cortical bone, in ovariectomized mice fed standard diet. Preosteoblastic MC3T3-E1 cells exhibited increased cellular proliferation and viability and alkaline phosphatase activity after treatment with sera from animals fed HFD.

CONCLUSIONS:

Endogenous estrogens partially reduce atherogenic burden in female apolipoprotein E-deficient mice. Ovariectomy increases bone resorption, but not under exacerbated proatherogenic conditions induced by HFD. The absence of apolipoprotein E might have an influence on the asymmetric responses of atherogenesis and bone resorption.

• Authors: María Leonor Fernández-Murga, Ángela Vinué, José Ramón Caeiro, David Guede, Juan J Tarín, Vicente Andrés, Antonio Cano
• Journal: Menopause (New York, N.Y.) (Menopause) Vol. 22 Issue 4 Pg. 428-36 (Apr 2015) ISSN: 1530-0374 [Electronic] United States
• PMID: 25203894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Estrogens

Topics

• Animals
• Apolipoproteins E (deficiency)
• Atherosclerosis (metabolism, prevention & control)
• Bone Density
• Bone Resorption
• Diet, High-Fat
• Disease Models, Animal
• Estrogens (physiology)
• Female
• Humans
• Mice
• Osteoporosis (prevention & control)
• Ovariectomy