Abstract
Proto-oncogene (c-fos, c-jun) and nuclear factor-kappa B (NF-kappaB) expression, as well as DNA synthesis, in aortic and cerebral vascular smooth muscle cells (VSMCs) were upregulated by a decrease in extracellular magnesium ions ([Mg2+]o). Upregulation of these transcriptional factors was inversely proportional to the [Mg2+]o and occurred over the pathophysiologic range of serum Mg2+ found in patients presenting with hypertension, ischemic heart disease, and stroke. Removal of extracellular Ca2+ ([Ca2+]o), use of nifedipine or protein kinase C (PKC) inhibitors prevented the upregulation of the proto-oncogenes and DNA synthesis in VSMCs. These data show that [Mg2+]o may be an important, heretofore, overlooked natural modulator of proto-oncogene and NF-kappaB expression in VSMCs and that Ca2+ and PKC may play critical roles in induction of c-fos and c-jun in VSMCs induced by a decrease in [Mg2+]o. These results point to a role for low serum Mg2+ in potential development of hypertension, atherogenesis, vascular disease, and stroke.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Aorta, Thoracic / drug effects*
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Aorta, Thoracic / metabolism*
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Biomarkers / analysis
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Calcium / metabolism
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Calcium / pharmacology
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Calcium Channel Blockers / pharmacology
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Cardiovascular Diseases
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DNA / biosynthesis
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DNA / drug effects
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Disease Models, Animal
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Dogs
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Extracellular Space / metabolism*
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Genes, fos / drug effects*
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Genes, fos / physiology*
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Genes, jun / drug effects*
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Genes, jun / physiology*
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Hypertension / metabolism
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Magnesium / metabolism*
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Magnesium / pharmacology*
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Male
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Muscle, Smooth, Vascular / cytology*
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Muscle, Smooth, Vascular / drug effects*
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Myocardial Ischemia / metabolism
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Myocytes, Smooth Muscle / drug effects*
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Myocytes, Smooth Muscle / metabolism*
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NF-kappa B / biosynthesis*
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NF-kappa B / drug effects*
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Nifedipine / pharmacology
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Protein Kinase C / antagonists & inhibitors
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Stroke / metabolism
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Telencephalon / cytology*
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Telencephalon / drug effects*
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Time Factors
Substances
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Biomarkers
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Calcium Channel Blockers
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Enzyme Inhibitors
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NF-kappa B
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RNA, Messenger
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DNA
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Protein Kinase C
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Magnesium
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Nifedipine
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Calcium