title: Superoxide-mediated activation of cardiac fibroblasts by serum factors in hypomagnesemia.
abstract: Magnesium deficiency is known to produce myocardial fibrosis in different animal models, but the underlying mechanisms are unclear. However, circulating levels of pro-oxidant and mitogenic factors are reported to be elevated in a rodent model of acute magnesium deficiency, suggesting a role for humoral factors in the pathogenesis of the cardiovascular lesions. Probing the mechanism of cardiac fibrogenesis in magnesium deficiency, the present study furnished evidence that serum from magnesium-deficient rats has a more marked effect than serum from magnesium-sufficient rats on mitogenesis, net collagen production, and superoxide generation in cardiac fibroblasts from young adult rats. The enhanced mitogenic response was abolished by superoxide dismutase and N-acetyl cysteine, showing that it is mediated by superoxide anion. Further, a modest inhibitory effect of the neurokinin-1 receptor antagonist, spantide, suggested that factors acting via neurokinin-1 receptors may partly modulate cardiac fibroblast function in magnesium deficiency. The findings are consistent with the postulation that serum factors may activate cardiac fibroblasts via a superoxide-mediated mechanism and contribute to the fibrogenic response in the heart in magnesium deficiency.
authors.affiliation: Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India 695 011.
authors.forename: C
authors.initials: C
authors.lastname: Kumaran
authors.forename: K
authors.initials: K
authors.lastname: Shivakumar
mesh_terms: D000818:Animals; D002455:Cell Division; D003094:Collagen / Q000096:biosynthesis; D003545:Cysteine / Q000378:metabolism / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D008275:Magnesium Deficiency / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010949:Plasma / Q000378:metabolism; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D018040:Receptors, Neurokinin-1; D013481:Superoxides; D003094:Collagen; D013482:Superoxide Dismutase; D003545:Cysteine