Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans

Abstract

Active matrix Gla protein (MGP), a potent inhibitor of calcification in large arteries, protects against macrovascular complications. Recent studies suggested that active MGP helps maintaining the integrity of the renal and myocardial microcirculation, but its role in preserving the retinal microcirculation remains unknown. In 935 randomly recruited Flemish participants (mean age, 40.9 years; 50.3% women), we measured plasma desphospho-uncarboxylated MGP (dp–ucMGP), a marker of poor vitamin K status using an ELISA-based assay at baseline (1996–2010) and retinal microvascular diameters using IVAN software (Vasculomatic ala Nicola, version 1.1) including the central retinal arteriolar (CRAE) and venular (CRVE) equivalent and the arteriole-to-venule ratio (AVR) at follow-up (2008–2015). CRAE (P = 0.005) and AVR (P = 0.080) at follow-up decreased across tertiles of the dp–ucMGP distribution. In unadjusted models, for a doubling of dp–ucMGP at baseline, CRAE and AVR at follow-up respectively decreased by 1.40 µm (95% confidence interval [CI], 0.32 to 2.48; P = 0.011) and 0.006 (CI, 0.001 to 0.011; P = 0.016). In multivariable-adjusted models accounting for sex, baseline characteristics and follow-up duration, these estimates were −1.03 µm (CI, −1.96 to −0.11; P = 0.028) and −0.007 (CI, −0.011 to −0.002; P = 0.007). Additional adjustment for changes from baseline to follow-up in major baseline characteristics yielded as estimates −0.91 µm (CI, −1.82 to −0.01; P = 0.048) and −0.006 (95% CI, −0.011 to −0.001; P = 0.014), respectively. Circulating inactive dp–ucMGP is a long-term predictor of smaller retinal arteriolar diameter in the general population. Our observations highlight the possibility that vitamin K supplementation might promote retinal health.

Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes

“…As observed by others, dp-ucMGP is associated negatively with eGFR estimated by MDRD and with albuminuria (S1 Table) [39,40]. However we don't find any association between dp-ucMGP and retinopathy treated by laser (S1 Table) despite some data suggesting that dp-ucMGP could be a marker of retinal health [42]. Additional studies are needed to explore specifically these associations in patients with diabetes.…”

The Effect of Dietary Vitamin K1 Supplementation on Trabecular Meshwork and Retina in a Chronic Ocular Hypertensive Rat Model

“…Basic and clinical studies have demonstrated the importance of appropriate vitamin K status for the health of the vascular system 23 and musculoskeletal tissues. 24 A recent study showed that circulating inactive dp-ucMGP is a long-term predictor of smaller retinal arteriolar diameter in the general population, 15 which highlights the potential role of vitamin K in retinal health. In the present study, dietary VitK1 supplementation can partially protect the apoptosis of RGCs from COH, which further confirmed the neuroprotective role of vitamin K. The beneficial effect of VitK1 may act through its antioxidative and anti-inflammatory effect, which warrants further investigation.…”

“…14 A recent study demonstrated that circulating dp-ucMGP (an inactive form of MGP protein that indirectly reflects the low vitamin K status) is a long-term predictor of smaller retinal arteriolar diameter in the general population, which highlights the potential beneficial effect of vitamin K supplementation in retinal health. 15 However, the pathophysiologic relationship between vitamin K and the optic neuropathy in glaucoma remains largely unknown.…”

Inactive matrix Gla protein is elevated in patients with inflammatory bowel disease

“…With high binding affinity to hydroxyapatite crystals, it is considered as one of the most important biological agents in the prevention of vascular calcification[ 11 - 13 ]. Furthermore, increased levels of its inactive dephosphorylated and uncarboxylated form, designated as dp-ucMGP, have been associated with number of different cardiovascular consequences and complications, including endothelial dysfunction, retinal arteriolar narrowing, atherosclerosis, increased aortic stiffness, and higher overall cardiovascular, non-cancer and total mortality[ 14 - 17 ].…”