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The Metabolic Syndrome / Cardiovascular Disease

Senior Researchers:

Dr. Elisabet Stener-Victorin

Associate Professor Åsa Tivesten

Professor Agneta Holmäng

Professor Suzanne Dickson

Professor John-Olov Jansson

Abundant evidence supports a role for SS in cardiovascular disease, either directly by affecting vascular function or indirectly through interactions with cardiovascular risk factors associated with the metabolic syndrome.

Effects of SS on cardiovascular risk factors (AH, SD, JOJ, JL)

Obesity and insulin resistance
SS regulate fat mass and affect insulin resistance by interactions with classic transcription-regulating nuclear SS receptors. However, the roles of recently discovered functional membrane-bound (G-protein-coupled) receptors for estrogens (GPR30) and progesterone (mPR alpha, beta, and gamma) in these processes is unknown. In this module, researchers will characterize the metabolic phenotype in mice in which the mPR or mER has been inactivated. If fat mass is altered, mechanistic studies will be performed, including analyses of energy expenditure, activity, food intake, and hypothalamic gene expression, and electrophysiology. Insulin sensitivity will be investigated with the clamp technique.

The role of both nuclear and membrane-bound SS receptors in early postnatal programming of adult insulin sensitivity and fat mass will be investigated by using SS-receptor-inactivated mice or pharmacological blockade of the different SS receptors.

The female hyperandrogenic metabolic syndrome PCOS (polycystic ovary syndrome), the most common endocrine disorder in women of reproductive age, is associated with insulin resistance, visceral obesity, and increased risk of cardiovascular disease. To explore the etiology of this disorder, which is unknown, the associations between PCOS, SS-related polymorphisms, SS metabolites, and environmental factors will be analyzed in a well-characterized cohort, including detailed information from birth records.

The independent relation between blood pressure and SS metabolites in serum and urine and SS-related polymorphisms will be examined in the MrOS-Sweden study (longitudinal, average age 75 years, n = 3000 men). The association with cardiovascular end points in this cohort will also be investigated.

Effects of SS on vascular function (HC, ÅT)
The researchers will study the role of SS and SS metabolites in vascular endothelial function (flow-mediated dilatation) and subclinical atherosclerosis (intima-media thickness) in a well-characterized clinical cohort (AIR, longitudinal, n = 391 men).

Mechanistic studies of the role of local SS receptors and SS metabolism in vessels will be investigated in mice with specific inactivation of endothelial SS receptors or enzymes involved in SS synthesis or degradation.

Since SS are important regulators of immunological responses and local immune reactions are pivotal for atherogenesis, SS might contribute to atherogenesis by immune-mediated mechanisms. To explore this hypothesis, the researchers will investigate the effect of SS in different mouse models in which different major components of the immune system have been inactivated.

Page Manager: Marie Lagerquist|Last update: 8/18/2011

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