Conflicting Forces of Warfarin and Matrix Gla Protein in the Artery Wall

Demer, Linda L.; Boström, Kristina I.

doi:10.1161/atvbaha.114.304793

Cited by 9 publications

(6 citation statements)

References 18 publications

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“…It is not yet clear how the different MGP functions relate to the calcification process, but may involve transglutaminase 2 and elastin fragmentation [48]. Interference with the gamma-carboxylation of MGP, which is susceptible to warfarin, might be a link between clinical warfarin use and vascular calcification [49]. …”

Section: Signaling Pathways and Relation Of Calcific Diseasementioning

confidence: 99%

Where do we stand on vascular calcification?

Boström

2016

Vascular Pharmacology

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Vascular disease, such as atherosclerosis and diabetic vasculopathy, is frequently complicated by vascular calcification. Previously believed to be an end-stage process of unregulated mineral precipitation, it is now well established to be a multi-faceted disease influenced by the characteristics of its vascular location, the origins of calcifying cells and numerous regulatory pathways. It reflects the fundamental plasticity of the vasculature that is gradually being revealed by progress in vascular and stem cell biology. This review provides a brief overview of where we stand in our understanding of vascular calcification, facing the challenge of translating this knowledge into viable preventive and therapeutic strategies.

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Section: Signaling Pathways and Relation Of Calcific Diseasementioning

confidence: 99%

Where do we stand on vascular calcification?

Boström

2016

Vascular Pharmacology

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“…Warfarin, a commonly used anticoagulant, appears to interfere with the function of MGP and may be involved in the dysregulation of fetuin A, osteopontin expression, pyrophosphate, and other molecular inhibitors. It may also be associated with altered mechanisms of balance between Ca/Pi and hormonal disorders, interacting with estradiol, insulin, or vitamin D3 [ 70 ].…”

Section: Molecular Mechanisms Underlying Vascular Calcifications Asso...mentioning

confidence: 99%

Mechanisms of Cardiovascular Calcification and Experimental Models: Impact of Vitamin K Antagonists

Siracusa,

Carino,

Carabetta

et al. 2024

JCM

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Cardiovascular calcification is a multifactorial and complex process involving an array of molecular mechanisms eventually leading to calcium deposition within the arterial walls. This process increases arterial stiffness, decreases elasticity, influences shear stress events and is related to an increased risk of morbidity and mortality associated with cardiovascular disease. In numerous in vivo and in vitro models, warfarin therapy has been shown to cause vascular calcification in the arterial wall. However, the exact mechanisms of calcification formation with warfarin remain largely unknown, although several molecular pathways have been identified. Circulating miRNA have been evaluated as biomarkers for a wide range of cardiovascular diseases, but their exact role in cardiovascular calcification is limited. This review aims to describe the current state-of-the-art research on the impact of warfarin treatment on the development of vascular calcification and to highlight potential molecular targets, including microRNA, within the implicated pathways.

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“…Inflammation also plays an important role in the calcification process, while macrophages, neutrophils, and T cells promote extracellular matrix remodeling,osteogenic differentiation and apoptosis of VSMCs [ 22 , 32 ]. A recent experimental study showed that statin therapy is related to increased coronary artery calcification by stimulating inflammasome and macrophages, leading to nuclear factor-k

(NF-k

) activation and the secretion of IL-1

mRNA and Rac1-depended IL-1

protein [ 33 , 34 ]. Racs are small GTPases and signal inflammatory transducers affecting the expression of growth factors and cytokines.…”

Section: Pathophysiologic Mechanisms Of Atherosclerotic and Arterial ...mentioning

confidence: 99%

The Complex Mechanisms and the Potential Effects of Statins on Vascular Calcification: A Narrative Review

Kadoglou,

Stasinopoulou,

Velidakis

et al. 2024

Rev. Cardiovasc. Med.

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Vascular calcification (VC) is a complex process of calcium deposition on the arterial wall and atherosclerotic plaques and involves interaction between vascular smooth muscle cells, inflammatory and VC mediators. The latter are independent predictors of cardiovascular morbidity and mortality and potential targets of pharmaceutical therapy. This paper is a narrative review of the complex mechanisms of VC development and in this context the potential anti-atherosclerotic effects of statins. At the initial stages of atherosclerosis VC correlates with atherosclerosis burden and in the long-term with cardiovascular morbidity and mortality. A plethora of animal and clinical studies have proposed statins as the cornerstone of primary and secondary prevention of atherosclerotic cardiovascular disease. Based on coronary computed tomography data, high doses of statins may have negligible or even positive effects on the progression of coronary artery calcification. Growing data support an increase in atherosclerotic plaque calcification in peripheral arteries (e.g., carotids), after long-term, statin-therapy. Despite the paradox of increasing VC, those effects of statins have been associated with higher plaque stability, reducing the risk of consequent adverse events. Statins seem to promote a “favorable” atherosclerotic calcification, suppressing atherosclerotic lesion expansion and their vulnerability. More studies are required to clarify the underlying mechanisms.

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Conflicting Forces of Warfarin and Matrix Gla Protein in the Artery Wall

Cited by 9 publications

References 18 publications

Where do we stand on vascular calcification?

Where do we stand on vascular calcification?

Mechanisms of Cardiovascular Calcification and Experimental Models: Impact of Vitamin K Antagonists

The Complex Mechanisms and the Potential Effects of Statins on Vascular Calcification: A Narrative Review

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