[Effect of glucose concentration on vascular function in aging. Action on calcium fluxes and vasomotricity induced by elastin peptides].
Glycemia is a physiological parameter tightly regulated for an optimal energetic supply to the organism, in spite of variable tissular glucose needs. Physiopathological alteration of glycemic regulation leads to dysfunctions of many cell types. For example, diabetes considerably increases morbidity and mortality linked to cardiovascular pathologies and constitute nowadays a serious public health problem. Many in vivo and in vitro studies have investigated the impact of extracellular glucose concentration on smooth muscle and endothelial cells. Glycemia regulates expression and activity of proteins implicated in various processes, such as vasodilation (eNOS), cellular adherence (ICAM-1, VCAM-1), glucose transport (GLUT-1) or free radical generation. Nuclear receptors of the PPAR (peroxisome proliferator-activated receptors) family which are implicated in glucose and lipid metabolism control, seem to have direct vascular actions, in the regulation of cellular functions by extracellular glucose, reinforcing their status of pharmacological targets for preservation and improvement of vascular function. More general processes, such as cellular proliferation and cell death, are also influenced by glucose concentration. Concerning the contractile function, hypoglycemia and hyperglycemia modulate vascular reactivity while acting on the vasoactive substances level and the cellular response to these molecules. In particular they act on variation of ionic channels (K+, Ca2+) activity or by interfering with some signaling pathways (NO). For example, the age-dependant vasodilation and endothelial calcium influx induced by elastin peptide are modulated by extracellular glucose levels. In conclusion, abnormal chronic variations of circulating glucose levels seem to be directly responsible for endothelial and smooth muscle cell dysfunction in the pathogenesis of cardiovascular abnormalities of patients presenting glycemia dysregulations.
Pezet
Mylène
M
Laboratoire Développement et Vieillissement de l'Endothelium, Université Joseph Fourier-EMI INSERM 0219-CEA, 17, rue des Martyrs, 38054 Grenoble Cedex 9, France.
Verdetti
Jean
J
Faury
Gilles
G
D000375:Aging / Q000097:blood / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000502:physiology*; D001808:Blood Vessels / Q000254:growth & development / Q000502:physiology* / Q000503:physiopathology; D020013:Calcium Signaling / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D003920:Diabetes Mellitus / Q000378:metabolism; D004549:Elastin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology; D007473:Ion Channels / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020025:Peroxisome Proliferators / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D001786:Blood Glucose; D007473:Ion Channels; D020025:Peroxisome Proliferators; D004549:Elastin; D005947:Glucose