Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperaldosteronism is associated with hypertension, cardiovascular fibrosis, and electrolyte disturbances, including hypomagnesemia. Mechanisms underlying aldosterone-mediated Mg(2+) changes are unclear, but the novel Mg(2+) transporters TRPM6 and TRPM7 may be important. We examined whether aldosterone influences renal TRPM6/7 and the TRPM7 downstream target annexin-1 and tested the hypothesis that Mg(2+) administration ameliorates aldosterone-induced cardiovascular and renal injury and prevents aldosterone-associated hypertension. C57B6 mice were studied (12 weeks, n=8 to 9/group); (1) control group (0.2% dietary Mg(2+)), (2) Mg(2+) group (0.75% dietary Mg(2+)), (3) aldosterone group (Aldo, 400 microg/kg/min and 0.9% NaCl drinking water), and (4) Aldo+Mg(2+) group. Blood pressure was unaltered by aldosterone and was similar in all groups throughout the experiment. Serum Na(+) was increased and serum K(+) and Mg(2+) decreased in the Aldo group. Aldo mice had hypomagnesuria and proteinuria, and renal, cardiac, and aortic fibrosis, which were normalized by Mg(2+) supplementation. Renal and cardiovascular expression of interleukin-6, VCAM1 and COX2 was increased in the Aldo group. Magnesium attenuated renal and cardiac interleukin-6 content and decreased renal VCAM1 and cardiac COX2 expression (P<0.05). Aldosterone decreased expression of renal TRPM7 and the downstream target annexin-1 (P<0.05) without effect on TRPM6. Whereas Mg(2+) increased mRNA expression of TRPM6 and TRPM7, it had no effect on TRPM7 and annexin-1 protein content. Our data demonstrate that aldosterone mediates blood pressure-independent renal and cardiovascular fibrosis and inflammation through Mg(2+)-sensitive pathways. We suggest that altered Mg(2+) metabolism in hyperaldosteronism may relate to TRPM7 downregulation and that Mg(2+) protects against cardiovascular and renal damaging actions of aldosterone.
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PMID:Downregulation of renal TRPM7 and increased inflammation and fibrosis in aldosterone-infused mice: effects of magnesium. 1826 39

Preeclampsia is a pregnancy-specific disorder characterized by de novo development of concurrent hypertension, proteinuria, and placental oxidative stress. During the last trimester of gestation, maternal-to-fetal transport of minerals is dramatically increased and becomes tightly mediated by ion channels that are highly permeable to various divalent cations, such as Ca(2+) , Mg(2+) , and Zn(2+) . The regulation of magnesium/inorganic phosphorus ion-channel transport in the placenta, however, is not incompletely understood. In the present study, we examined the regulation of magnesium/inorganic phosphorus channels (MPCs) in the placenta of pregnant women suffering from preeclampsia as well as in primary human placental cells subjected to oxidative stress. The expression of MPC genes (TRPM6, TRPM7, PiT-1, and PiT-2) was down-regulated in preeclamptic placenta tissues during preterm labor, and generally remained lower at term labor-although TRPM7 expression in the central placenta or PiT-2 expression in whole placenta was unchanged or up-regulated. Consistent with this association, expression of MPC genes in the primary placental cells was reduced under hypoxic conditions. TRPM6, TRPM7, and PiT-1 channels were predominantly detected in the syncytiotrophoblast layers of the placenta. In contrast, PiT-2 was abundant in the placental intravillous connective tissues. Taken together, our findings indicated that placental MPC expression is down-regulated in cases of preeclampsia and under hypoxia. This relationship may contribute to a better understanding of the interrelationship between magnesium/inorganic phosphorus imbalances and preeclampsia development during preterm or term labor.
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PMID:Comparing the expression patterns of placental magnesium/phosphorus-transporting channels between healthy and preeclamptic pregnancies. 2515 68