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New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs) Versus Direct Oral Anticoagulants (DOACs).

van Gorp RH, Schurgers LJ - Nutrients (2015)

Bottom Line: DOACs also display non-hemostatic vascular effects via protease-activated receptors (PARs).As atherosclerosis is characterized by a hypercoagulable state indicating the involvement of activated coagulation factors in the genesis of atherosclerosis, anticoagulation could have beneficial effects on atherosclerosis.Additionally, accumulating evidence demonstrates vascular benefit from high vitamin K intake.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. rick.vangorp@maastrichtuniversity.nl.

ABSTRACT
Vitamin K-antagonists (VKA) are the most widely used anticoagulant drugs to treat patients at risk of arterial and venous thrombosis for the past 50 years. Due to unfavorable pharmacokinetics VKA have a small therapeutic window, require frequent monitoring, and are susceptible to drug and nutritional interactions. Additionally, the effect of VKA is not limited to coagulation, but affects all vitamin K-dependent proteins. As a consequence, VKA have detrimental side effects by enhancing medial and intimal calcification. These limitations stimulated the development of alternative anticoagulant drugs, resulting in direct oral anticoagulant (DOAC) drugs, which specifically target coagulation factor Xa and thrombin. DOACs also display non-hemostatic vascular effects via protease-activated receptors (PARs). As atherosclerosis is characterized by a hypercoagulable state indicating the involvement of activated coagulation factors in the genesis of atherosclerosis, anticoagulation could have beneficial effects on atherosclerosis. Additionally, accumulating evidence demonstrates vascular benefit from high vitamin K intake. This review gives an update on oral anticoagulant treatment on the vasculature with a special focus on calcification and vitamin K interaction.

No MeSH data available.


Related in: MedlinePlus

Similarities in bone metabolism and vascular calcification. The calcification process can be divided into three stages: initiation, nucleation and crystal growth. In order to initiate mineralization resting chondrocytes and contractile vascular smooth muscle cells (VSMCs) lose calcification inhibitors. Moreover, vesicles derived from chondrocytes and VSMCs form a nidus for calcification. In both bone metabolism and vascular calcification the matrix plays an important role in the nucleation stage. In bone metabolism, an osteoblast matrix results in proliferation of chondrocytes. Likewise, a calcifying matrix consisting of elastin, collagen and Ca2+ and P accompany vascular calcification. Additionally, contractile VSMCs undergo phenotypic switching resulting in synthetic VSMCs, which have increased proliferation and migration in comparison to contractile VSMCs. Finally, osteoblasts and osteochondrogenic VSMCs induce crystal growth in bone metabolism and vascular calcification, respectively.
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nutrients-07-05479-f003: Similarities in bone metabolism and vascular calcification. The calcification process can be divided into three stages: initiation, nucleation and crystal growth. In order to initiate mineralization resting chondrocytes and contractile vascular smooth muscle cells (VSMCs) lose calcification inhibitors. Moreover, vesicles derived from chondrocytes and VSMCs form a nidus for calcification. In both bone metabolism and vascular calcification the matrix plays an important role in the nucleation stage. In bone metabolism, an osteoblast matrix results in proliferation of chondrocytes. Likewise, a calcifying matrix consisting of elastin, collagen and Ca2+ and P accompany vascular calcification. Additionally, contractile VSMCs undergo phenotypic switching resulting in synthetic VSMCs, which have increased proliferation and migration in comparison to contractile VSMCs. Finally, osteoblasts and osteochondrogenic VSMCs induce crystal growth in bone metabolism and vascular calcification, respectively.

Mentions: Like all VKDP proteins, OC requires vitamin K for the γ-glutamylcarboxylation of three glutamate-residues, which in turn confers functional protein activity. In tissues and the circulation OC is present in both the carboxylated (cOC) and uncarboxylated (ucOC) conformations. OC is mostly associated with bone metabolism [95] where it promotes bone growth [96,97,98]. The processes of bone metabolism and soft tissue calcification are closely related, suggesting a possible role of osteocalcin in vascular calcification (Figure 3). As in bone metabolism, OC is thought to both promote [99] and inhibit [100,101,102,103] soft tissue calcification in order to regulate remodeling and mineralization [104]. It has been suggested that the inhibitory effect of OC on calcification is via mechanisms that prevent calcium and phosphate precipitation [17].


New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs) Versus Direct Oral Anticoagulants (DOACs).

van Gorp RH, Schurgers LJ - Nutrients (2015)

Similarities in bone metabolism and vascular calcification. The calcification process can be divided into three stages: initiation, nucleation and crystal growth. In order to initiate mineralization resting chondrocytes and contractile vascular smooth muscle cells (VSMCs) lose calcification inhibitors. Moreover, vesicles derived from chondrocytes and VSMCs form a nidus for calcification. In both bone metabolism and vascular calcification the matrix plays an important role in the nucleation stage. In bone metabolism, an osteoblast matrix results in proliferation of chondrocytes. Likewise, a calcifying matrix consisting of elastin, collagen and Ca2+ and P accompany vascular calcification. Additionally, contractile VSMCs undergo phenotypic switching resulting in synthetic VSMCs, which have increased proliferation and migration in comparison to contractile VSMCs. Finally, osteoblasts and osteochondrogenic VSMCs induce crystal growth in bone metabolism and vascular calcification, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663607&req=5

nutrients-07-05479-f003: Similarities in bone metabolism and vascular calcification. The calcification process can be divided into three stages: initiation, nucleation and crystal growth. In order to initiate mineralization resting chondrocytes and contractile vascular smooth muscle cells (VSMCs) lose calcification inhibitors. Moreover, vesicles derived from chondrocytes and VSMCs form a nidus for calcification. In both bone metabolism and vascular calcification the matrix plays an important role in the nucleation stage. In bone metabolism, an osteoblast matrix results in proliferation of chondrocytes. Likewise, a calcifying matrix consisting of elastin, collagen and Ca2+ and P accompany vascular calcification. Additionally, contractile VSMCs undergo phenotypic switching resulting in synthetic VSMCs, which have increased proliferation and migration in comparison to contractile VSMCs. Finally, osteoblasts and osteochondrogenic VSMCs induce crystal growth in bone metabolism and vascular calcification, respectively.
Mentions: Like all VKDP proteins, OC requires vitamin K for the γ-glutamylcarboxylation of three glutamate-residues, which in turn confers functional protein activity. In tissues and the circulation OC is present in both the carboxylated (cOC) and uncarboxylated (ucOC) conformations. OC is mostly associated with bone metabolism [95] where it promotes bone growth [96,97,98]. The processes of bone metabolism and soft tissue calcification are closely related, suggesting a possible role of osteocalcin in vascular calcification (Figure 3). As in bone metabolism, OC is thought to both promote [99] and inhibit [100,101,102,103] soft tissue calcification in order to regulate remodeling and mineralization [104]. It has been suggested that the inhibitory effect of OC on calcification is via mechanisms that prevent calcium and phosphate precipitation [17].

Bottom Line: DOACs also display non-hemostatic vascular effects via protease-activated receptors (PARs).As atherosclerosis is characterized by a hypercoagulable state indicating the involvement of activated coagulation factors in the genesis of atherosclerosis, anticoagulation could have beneficial effects on atherosclerosis.Additionally, accumulating evidence demonstrates vascular benefit from high vitamin K intake.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. rick.vangorp@maastrichtuniversity.nl.

ABSTRACT
Vitamin K-antagonists (VKA) are the most widely used anticoagulant drugs to treat patients at risk of arterial and venous thrombosis for the past 50 years. Due to unfavorable pharmacokinetics VKA have a small therapeutic window, require frequent monitoring, and are susceptible to drug and nutritional interactions. Additionally, the effect of VKA is not limited to coagulation, but affects all vitamin K-dependent proteins. As a consequence, VKA have detrimental side effects by enhancing medial and intimal calcification. These limitations stimulated the development of alternative anticoagulant drugs, resulting in direct oral anticoagulant (DOAC) drugs, which specifically target coagulation factor Xa and thrombin. DOACs also display non-hemostatic vascular effects via protease-activated receptors (PARs). As atherosclerosis is characterized by a hypercoagulable state indicating the involvement of activated coagulation factors in the genesis of atherosclerosis, anticoagulation could have beneficial effects on atherosclerosis. Additionally, accumulating evidence demonstrates vascular benefit from high vitamin K intake. This review gives an update on oral anticoagulant treatment on the vasculature with a special focus on calcification and vitamin K interaction.

No MeSH data available.


Related in: MedlinePlus