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.

Keywords: arteriosclerosis; cardiovascular diseases; carotid arteries; nutrition; stroke.

Figure 1

Oral magnesium (Mg) administration reduced CIMT in Abcc6^−/− mice and the rate of CIMT change is measurable in this mineralizing disorder. (A) 12‐month‐old carotid artery section from wild type (WT, Abcc6^+/+) controls (untreated).10 (B) 12‐month‐old carotid artery section from knockout (KO) controls (untreated; p < 0.009 compared to [A]).10 (C) 12‐month‐old carotid artery section from WT‐treated. (D) 12‐month‐old carotid artery section from KO treated with 2 months of oral Mg (p < 0.02 compared to [B]).10 (E) 15‐month‐old carotid artery section from a KO control mouse (untreated). (F) 15‐month‐old carotid artery section from KO mouse treated 2 months on, 2 months off with Mg (p < 0.011 compared to [E]). The mean value in (F), 118 μm, as well as the individual value shown, 119 μm, were similar to that of (B), the 12‐month‐old Abcc6 ^−/− untreated group, mean 120 μm. The bar represents 100 μm.