title: Rate of change of carotid intima-media thickness with magnesium administration in Abcc6⁻/⁻ mice.
abstract: Pseudoxanthoma elasticum (PXE), caused by mutations in the ABCC6 gene, demonstrates progressive build-up of calcium phosphate and proteoglycans in the skin, eye, and arteries, and is associated to myocardial infarctions, stroke, blindness, and elevated carotid intima-media thickness (CIMT). Although CIMT reduction with magnesium (Mg) has been documented in a mouse model for PXE (Abcc6(-/-) ), it is not clear if Mg is effective in humans with PXE to reduce CIMT. To examine this, we calculated the rate of change of CIMT (washout) in 15- and 12-month-old Abcc6(-/-) mice fed standard rodent diet with or without Mg supplementation for 2 months. Using means in untreated 15- and 12-month-old Abcc6(-/-) mice (145 and 120 μm, respectively), the rate of change was 8.3 μm/month. Using means in treated 15- and 12-month-old Abcc6(-/-) mice (118 and 104.6 μm, respectively), the rate of change was 4.5 μm. Compared to normal progression of CIMT in humans without PXE, PXE has advanced atherosclerosis and possibly a higher CIMT rate of change. This experiment may portend, at least in PXE, the rationale for a 1-year oral Mg CIMT clinical trial and may be useful for application in other progressive mineralizing disorders like atherosclerosis.
authors: Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors: Erine A
authors: EA
authors: Kupetsky
authors: Fred
authors: F
authors: Rincon
authors: Jouni
authors: J
authors: Uitto
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D004195:Disease Models, Animal; D008277:Magnesium Oxide / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011561:Pseudoxanthoma Elasticum / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D018528:ATP-Binding Cassette Transporters; D008277:Magnesium Oxide; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C504743:Abcc6 protein, mouse
keywords: arteriosclerosis; cardiovascular diseases; carotid arteries; nutrition; stroke