Effects of Menopause and High Fat Diet on Metabolic Outcomes in a Mouse Model of Alzheimer's Disease.

Background: About two-thirds of those with Alzheimer's disease (AD) are women, most of whom are post-menopausal. Menopause accelerates dementia risk by increasing the risk for metabolic, cardiovascular, and cerebrovascular diseases. Mid-life metabolic disease (obesity, diabetes/prediabetes) is a well-known risk factor for dementia.

Whole mount of adult ear skin as a model to study vascular malformations.

Background: Genetic analysis in human patients has linked mutations in PIK3CA, the catalytic subunit of PI-3'Kinase, to sporadic incidences of vascular malformations.

Methods: We have developed a mouse model with inducible and endothelial-specific expression of PIK3CA , resulting in the development of vascular malformations. Systemic induction of this mutation in adult mice results in rapid lethality, limiting our ability to track and study these lesions; therefore, we developed a topical and local induction protocol using the active metabolite of tamoxifen, 4OH-T, on the ear skin of adults.

Laminin-511 and α6 integrins regulate the expression of CXCR4 to promote endothelial morphogenesis.

During angiogenesis, endothelial cells engage components of the extracellular matrix through integrin-mediated adhesion. Endothelial expression of laminin-411 and laminin-511 is known to promote vessel stability. However, little is known about the contribution of these laminins to endothelial morphogenesis.

Activation of Ras in the Vascular Endothelium Induces Brain Vascular Malformations and Hemorrhagic Stroke.

Cerebrovascular malformations (CVMs) affect approximately 3% of the population, risking hemorrhagic stroke, seizures, and neurological deficits. Recently Ras mutations have been identified in a majority of brain arterio-venous malformations. We generated an endothelial-specific, inducible HRAS mouse model, which results in dilated, proliferative blood vessels in the brain, blood-brain barrier breakdown, intracerebral hemorrhage, and rapid lethality.

mTORc1 activity is necessary and sufficient for phosphorylation of eNOS.

Nitric oxide, produced by eNOS, plays critical roles in the regulation of vascular function and maintenance. Chronic PI3K signaling has recently been associated with vascular malformations. A well described substrate downstream of PI3K signaling is eNOS.