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Editorial
. 2022 Feb;42(2):223-226.
doi: 10.1161/ATVBAHA.121.317206. Epub 2021 Dec 30.

Matrix GIa Protein, Large Artery Stiffness, and the Risk of Heart Failure With Preserved Ejection Fraction

Julio A Chirinos  1
Affiliations
Editorial

Matrix GIa Protein, Large Artery Stiffness, and the Risk of Heart Failure With Preserved Ejection Fraction

Julio A Chirinos. Arterioscler Thromb Vasc Biol. 2022 Feb.

Erratum in

No abstract available

Keywords: Editorials; heart failure; mortality; public health; quality of life; therapeutics.

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Figures

Figure
Figure
Matrix GIa protein (MGP) maturation involves serial post-translational γ-glutamate carboxylation (by vitamin K-dependent γ-glutamyl carboxylase, GGCX), and serine phosphorylation, leading to the formation of pc-MGP (phosphorylated, carboxylated MGP), which is a strong inhibitor of vascular calcification via direct inhibition of calcium deposition, bone morphogenetic protein 2 (BMP-2) signaling and vascular smooth muscle cell (VSMC) osteogenic-differentiation. Vitamin K deficiency (orange arrows) in the vascular wall leads to the formation of uncarboxylated (uc-) MGP and dephosphorylated, uncarboxylated (dpuc-)MGP, which are inactive MGP forms that can be detected in the circulation. As reported by Malhotra et al., MGP also inhibits collagen-1 expression in VSMCs (although the figure shows this as an effect of pcMGP, it has not been established whether post-translational MGP carboxylation or phosphorylation are required for this effect). Vascular effects of MGP deficiency can lead to increased large artery stiffening, which in turn promotes LV remodeling and failure via abnormal pulsatile arterial load, and various comorbidities (such as cognitive dysfunction and chronic kidney disease) via transmission of increased arterial pulsatility to low-resistance vascular beds, with subsequent microvascular damage. Increased levels of inactive MGP may also be a marker for subclinical vitamin K2 deficiency, which could lead to subtle mitochondrial myopathy and reduced skeletal muscle mass, potentially contributing to the development of HFpEF independent of MGP effects (see text for details).
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Comment on

  • Matrix Gla Protein Levels Are Associated With Arterial Stiffness and Incident Heart Failure With Preserved Ejection Fraction.
    Malhotra R, Nicholson CJ, Wang D, Bhambhani V, Paniagua S, Slocum C, Sigurslid HH, Lino Cardenas CL, Li R, Boerboom SL, Chen YC, Hwang SJ, Yao C, Ichinose F, Bloch DB, Lindsay ME, Lewis GD, Aragam JR, Hoffmann U, Mitchell GF, Hamburg NM, Vasan RS, Benjamin EJ, Larson MG, Zapol WM, Cheng S, Roh JD, O'Donnell CJ, Nguyen C, Levy D, Ho JE. Malhotra R, et al. Arterioscler Thromb Vasc Biol. 2022 Feb;42(2):e61-e73. doi: 10.1161/ATVBAHA.121.316664. Epub 2021 Nov 23. Arterioscler Thromb Vasc Biol. 2022. PMID: 34809448 Free PMC article.

References

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