Vascular signaling pathways in the metabolic syndrome.
There are several potential cellular and molecular pathways whereby cardiovascular risk factors act through very specific signal transduction pathways in the formation of atherosclerosis, as seen often in the metabolic syndrome. Many examples point to multiple postreceptor defects in the insulin signaling pathway in vascular tissue, however, there are differences in the insulin receptor pathway in vascular tissue compared with skeletal muscle or fat. In addition to insulin receptors, insulin may affect atherosclerotic changes in the vascular cells via stimulation of insulin-like growth factor-1 receptors and their signaling pathway. Insulin also causes activation of the vascular renin-angiotensin system in both vascular smooth muscle cells and endothelial cells. Insulin-activated tissue renin-angiotensin system leads to increased cell growth and contributes to the cause of atherosclerosis. The fact that agents that inhibit the renin-angiotensin system also block insulin-mediated renin-angiotensin system expression and cell growth reinforces the potential implication of a vascular insulin-renin-angiotensin system pathway. Finally, novel substances such as the adipokines, factors produced from fat cells, reveal new risk factors in the metabolic syndrome and offer further evidence for a link between insulin resistance and accelerated atherosclerosis.
Rakugi
Hiromi
H
Department of Geriatric Medicine (B6), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. rakugi@geriat.med.osaka-u.ac.jp
Kamide
Kei
K
Ogihara
Toshio
T
D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008659:Metabolic Diseases / Q000150:complications / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology; D012307:Risk Factors; D015398:Signal Transduction; D013577:Syndrome