Abstract
Specific patient cohorts are at increased risk of vascular calcification. Functional matrix-gla protein (MGP), a tissue-derived vitamin K dependent protein, is reported to be an important inhibitor of vascular calcification and may have clinical potential to modify the progression of vascular calcification through regulation of functional MGP fractions. This systematic review examines twenty-eight studies which assess the relationship between circulating protein expressions of MGP species and vascular calcification in different arterial beds. The included studies examined participants with atherosclerosis, chronic kidney disease (CKD), diabetes, healthy participants, vitamin K supplementation, measured plasma vitamin K levels and vitamin K antagonist usage. The current review reports conflicting results regarding MGP fractions with respect to local calcification development indicating that a multifaceted relationship exists between the MGP and calcification. A primary concern regarding the studies in this review is the large degree of variability in the calcification location assessed and the fraction of MGP measured. This review suggests that different underlying molecular mechanisms can accelerate local disease progression within the vasculature, and specific circulating fractions of MGP may be influenced differently depending on the local disease states related to vascular calcification development. Further studies examining the influence of non-functional MGP levels, with respect to specific calcified arterial beds, are warranted.
Highlights
Abating fatal cardiovascular disease (CVD) events among patients with atherosclerosis, chronic kidney disease, diabetes and the aging population remains an imperative clinical challenge.CVD induces major arterial occlusions and stiffening, which can be largely driven by the development of vascular calcification, and the associated hemodynamic consequences cause high rates of hypertension, myocardial infarction, stroke and lower-limb ischemia [1,2]
This conversion is necessary for the functionality of all vitamin K-dependent proteins (VKDPs) including, matrix-Gla-Protein (MGP), a 14 kDa VKDP, which is secreted primarily by vascular smooth muscle cells (VSMCs) in the arterial medial layer [6] and is considered a potent inhibitor of vascular calcification
The clinical trials articles included in this review report on vitamin K supplementation with respect to the progression of vascular calcification and changes in MGP levels have reported conflicting outcomes
Summary
Abating fatal cardiovascular disease (CVD) events among patients with atherosclerosis, chronic kidney disease, diabetes and the aging population remains an imperative clinical challenge.CVD induces major arterial occlusions and stiffening, which can be largely driven by the development of vascular calcification, and the associated hemodynamic consequences cause high rates of hypertension, myocardial infarction, stroke and lower-limb ischemia [1,2]. Vitamin K plays an integral role in the regulation of proteins associated with the inhibition of cardiovascular disease related complications [5]. It acts as a cofactor for the enzyme γ-glutamyl carboxylase in the post-translational conversion of glutamic acid (Glu) to γ-carboxyglutamic acid (Gla) residues. This conversion is necessary for the functionality of all vitamin K-dependent proteins (VKDPs) including, matrix-Gla-Protein (MGP), a 14 kDa VKDP, which is secreted primarily by vascular smooth muscle cells (VSMCs) in the arterial medial layer [6] and is considered a potent inhibitor of vascular calcification. Early detection in high risk patients prone to calcification development may act as a useful adjunctive criterion, allowing for early clinical intervention [12]
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