Magnesium reduces carotid intima-media thickness in a mouse model of pseudoxanthoma elasticum: a novel treatment biomarker.
Pseudoxanthoma elasticum (PXE), which demonstrates progressive build-up of calcium phosphate and proteoglycan deposits in skin, eye, and arteries, has been associated with myocardial infarctions, stroke, and blindness. In a mouse model of PXE, a magnesium-enriched diet prevents mineralization of the vibrissae capsule, an early biomarker for PXE. However, biomarkers for therapeutic responses in PXE have not been identified in humans. Because PXE patients have an increased carotid intima-media thickness (CIMT), a risk factor for cardiovascular disease and stroke, we analyzed the feasibility of CIMT as a treatment endpoint before and after magnesium supplementation in a mouse model of PXE (Abcc6(-/-) ). CIMT was measured in 1-year-old Abcc6(-/-) and Abcc6(+/+) mice fed either standard rodent diet with or without magnesium oxide supplementation for 2 months. Baseline CIMT in Abcc6(-/-) versus Abcc6(+/+) mice was increased (p value = 0.009), whereas CIMT in magnesium-treated versus untreated Abcc6(-/-) mice was reduced (p value = 0.024). CIMT is a novel treatment endpoint in this mouse model and may serve as a predictive biomarker of therapeutic response in PXE patients. In that context, magnesium oxide significantly reduced CIMT in PXE mice, and may be useful for disease prevention in PXE patients.
Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. erine.kupetsky-rincon@jefferson.edu
Erine A
EA
Kupetsky-Rincon
Qiaoli
Q
Li
Jouni
J
Uitto
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002130:Calcium Phosphates / Q000378:metabolism; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D004195:Disease Models, Animal; D008277:Magnesium Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011509:Proteoglycans / Q000378:metabolism; D011561:Pseudoxanthoma Elasticum / Q000000981:diagnostic imaging / Q000188:drug therapy*; D013194:Staining and Labeling; D014738:Vibrissae / Q000473:pathology
D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D002130:Calcium Phosphates; D008277:Magnesium Oxide; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011509:Proteoglycans; C504743:Abcc6 protein, mouse