Osteogenic transdifferentiation of vascular smooth muscle cells isolated from spontaneously hypertensive rats and potential menaquinone‐4 inhibiting effect

Mandatori, Domitilla; Pipino, Caterina; Tomo, Pamela Di; Schiavone, Valeria; Ranieri, Antonia; Pantalone, Sara; Silvestre, Sara Di; Pietrantonio, Nadia Di; Ucci, Mariangela; Palmerini, Carola; Failli, Paola; Pietro, Natalia Di; Pandolfi, Assunta

doi:10.1002/jcp.28576

Cited by 8 publications

(7 citation statements)

References 56 publications

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“…The inhibitory role of combined PB and vitamin K2 can be explained via a mechanism other than MGP activation. It has been shown that vitamin K protects VSMC differentiation and calcification into an osteogenic phenotype under a high phosphate environment via downregulation of bone-specific genes [37,38]. However, we could not find such an effect in our study (data not shown).…”

Section: Discussioncontrasting

confidence: 86%

Combining phosphate binder therapy with vitamin K2 inhibits vascular calcification in an experimental animal model of kidney failure

Neradová

Wasilewski

Prisco

et al. 2021

Nephrology Dialysis Transplantation

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Background Hyperphosphatemia is strongly associated with cardiovascular disease and mortality. Recently, phosphate binders (PBs), which are used to bind intestinal phosphate have been shown also to bind vitamin K, thereby potentially aggravating vitamin K deficiency. This vitamin K-binding by PBs may offset beneficial effects of phosphate level reduction on reducing vascular calcification (VC). Here we assessed whether combining PBs with vitamin K2 supplementation inhibits VC. Methods We performed 3/4Nx in rats, after which warfarin was given for three weeks to induce vitamin K-deficiency. Next, animals were fed a high phosphate diet in the presence of low or high vitamin K2 and were randomized to either control or one of four different PBs for eight weeks. Primary outcome was the amount of thoracic and abdominal aorta VC measured by high-resolution micro-Computed Tomography (μ-CT). Vitamin K status was measured by plasma MK7 levels and immunohistochemically analyzed in vasculature using ucMGP specific antibodies. Results Combination of high vitamin K2 diet and PB treatment significantly reduced VC as measured by μ-CT, for both thoracic (p = 0.026) and abdominal aorta (p = 0.023), compared to MK7 or PB treatment alone. UcMGP stain was significantly more present in the low vitamin K2 treated groups in both thoracic (p<0.01) and abdominal aorta (p<0.01) as compared to high vitamin K2 treated groups. Moreover, high vitamin K diet and PBs led to reduced vascular oxidative stress. Conclusion In an animal model of kidney failure with vitamin K-deficiency, neither PB therapy nor vitamin K2 supplementation alone prevented VC. However, the combination of high vitamin K2 with PB treatment significantly attenuated VC.

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Section: Discussioncontrasting

confidence: 86%

Combining phosphate binder therapy with vitamin K2 inhibits vascular calcification in an experimental animal model of kidney failure

Neradová

Wasilewski

Prisco

et al. 2021

Nephrology Dialysis Transplantation

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“…The latter is secreted by VSMCs and inhibits VC through poorly studied mechanisms [ 53 ]. These findings support a protective role for vitamin K in VC and this has been confirmed by numerous other studies [ 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ].…”

Section: Role Of Nuclear Receptors In Vascular Calcificationsupporting

confidence: 89%

Roles of Nuclear Receptors in Vascular Calcification

Chinetti-Gbaguidi

Neels

2021

IJMS

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Vascular calcification is defined as an inappropriate accumulation of calcium depots occurring in soft tissues, including the vascular wall. Growing evidence suggests that vascular calcification is an actively regulated process, sharing similar mechanisms with bone formation, implicating both inhibitory and inducible factors, mediated by osteoclast-like and osteoblast-like cells, respectively. This process, which occurs in nearly all the arterial beds and in both the medial and intimal layers, mainly involves vascular smooth muscle cells. In the vascular wall, calcification can have different clinical consequences, depending on the pattern, localization and nature of calcium deposition. Nuclear receptors are transcription factors widely expressed, activated by specific ligands that control the expression of target genes involved in a multitude of pathophysiological processes, including metabolism, cancer, inflammation and cell differentiation. Some of them act as drug targets. In this review we describe and discuss the role of different nuclear receptors in the control of vascular calcification.

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“…Interestingly, we found that MK-4 reduced VC progression, preserving the contractile phenotype SHR-VSMCs. Specifically, we demonstrated for the first time that treatment with MK-4 was able to decrease the VC process through the inhibition of VSMC osteoblast trans-differentiation via MGP carboxylation, which triggered the inhibition of BMP-2 [140].…”

Section: Vitamin K2 and Vascular Healthmentioning

confidence: 94%

The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification

et al. 2021

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Osteoporosis (OP) and vascular calcification (VC) represent relevant health problems that frequently coexist in the elderly population. Traditionally, they have been considered independent processes, and mainly age-related. However, an increasing number of studies have reported their possible direct correlation, commonly defined as “bone-vascular crosstalk”. Vitamin K2 (VitK2), a family of several natural isoforms also known as menaquinones (MK), has recently received particular attention for its role in maintaining calcium homeostasis. In particular, VitK2 deficiency seems to be responsible of the so-called “calcium paradox” phenomenon, characterized by low calcium deposition in the bone and its accumulation in the vessel wall. Since these events may have important clinical consequences, and the role of VitK2 in bone-vascular crosstalk has only partially been explained, this review focuses on its effects on the bone and vascular system by providing a more recent literature update. Overall, the findings reported here propose the VitK2 family as natural bioactive molecules that could be able to play an important role in the prevention of bone loss and vascular calcification, thus encouraging further in-depth studies to achieve its use as a dietary food supplement.

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Osteogenic transdifferentiation of vascular smooth muscle cells isolated from spontaneously hypertensive rats and potential menaquinone‐4 inhibiting effect

Cited by 8 publications

References 56 publications

Combining phosphate binder therapy with vitamin K2 inhibits vascular calcification in an experimental animal model of kidney failure

Combining phosphate binder therapy with vitamin K2 inhibits vascular calcification in an experimental animal model of kidney failure

Roles of Nuclear Receptors in Vascular Calcification

The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification

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