scholarly journals Potential Role for Osteocalcin in the Development of Atherosclerosis and Blood Vessel Disease

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1426 ◽  
Author(s):  
Alexander Tacey ◽  
Tawar Qaradakhi ◽  
Tara Brennan-Speranza ◽  
Alan Hayes ◽  
Anthony Zulli ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Undercarboxylated Osteocalcin ◽  
Vascular Cells ◽  
Metabolic Factors ◽  
Atherosclerotic Vascular Disease ◽  
Glucose And Lipid Metabolism ◽  
Metabolic Functions ◽  
Atherosclerosis Development ◽  
Phosphoinositide 3 Kinase

There is increasing evidence for the involvement of the skeleton in the regulation of atherosclerotic vascular disease. Osteocalcin, an osteoblast derived protein, exists in two forms, carboxylated and undercarboxylated osteocalcin. Undercarboxylated osteocalcin has been linked to the regulation of metabolic functions, including glucose and lipid metabolism. Features of atherosclerosis have been associated with circulating osteocalcin; however, this association is often conflicting and unclear. Therefore, the aim of this review is to examine the evidence for a role of osteocalcin in atherosclerosis development and progression, and in particular endothelial dysfunction and vascular calcification. The current literature suggests that undercarboxylated osteocalcin stimulates the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway to upregulate nitric oxide and nuclear factor kappa β (NF-кβ) in vascular cells, possibly protecting endothelial function and preventing atherogenesis. However, this effect may be mediated by metabolic factors, such as improvements in insulin signaling, rather than through a direct effect on the vasculature. Total osteocalcin is frequently associated with vascular calcification, an association that may occur as a result of vascular cells eliciting an osteogenic phenotype. Whether osteocalcin acts as a mediator or a marker of vascular calcification is currently unclear. As such, further studies that examine each form of osteocalcin are required to elucidate if it is a mediator of atherogenesis, and whether it functions independently of metabolic factors.

scholarly journals Role of calcification in aortic degeneration

2020 ◽  
Vol 7 (1) ◽  
pp. 6-21
Author(s):  
D. A. Kostina ◽  
V. E. Uspensky ◽  
D. S. Semenova ◽  
A. S. Kostina ◽  
N. V. Boyarskaya ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Signaling Pathways ◽  
Vascular Calcification ◽  
Vascular Pathology ◽  
Signal Pathways ◽  
Vascular Cells ◽  
Metabolic Dysfunction ◽  
Main Attention ◽  
Biological Regulation

Vascular calcification is a widely-spread pathology with high mortality. It is active bioregulated process that is observed in pathogenesis of different desires, associated with metabolic dysfunction, congenital tissue desires and aging. Signal pathways and transcription factors that are involved in vascular calcification are also takes place in normal osteogenesis and/or vascular development. In the review the main attention is payed to the role of signaling pathways BMP (bone morphogenic protein), Notch, Wnt and to the role of transcription factors BMP2, RUNX2, Msx2 in vascular calcification. Probably, dysfunction of osteogenic signal pathways and transdifferentiation of vascular cells to osteoblast-like cells is a common prosses not only for vascular calcification or mineralization, but is a way of vascular degradation in general. Proosteogenic changes at cellular and molecular level may play role in pathogenesis of a disease without manifestation of vascular mineralization, such as thoracic aortic aneurysm. Ability of vascular cells to change their phenotype to osteophenotype is very likely biologically important ability. Over weakness of calcific signaling pathways activity can also lead to vascular pathology. The aim of the review is to overlook the mechanisms of vascular calcification focusing at the role of signal pathways and vascular cells at this process with particular attention to aortic calcification. Understanding the mechanisms of biological regulation of pro- and antiosteogenic processes in pathology and normal conditions opens new opportunities to influence this prosess in order to correct vascular pathologies.

Thrombin Augments Vascular Cell-dependent Migration of Human Mast Cells: Role of MGF

1997 ◽  
Vol 77 (03) ◽  
pp. 577-584 ◽  
Author(s):  
Mehrdad Baghestanian ◽  
Roland Hofbauer ◽  
Hans G Kress ◽  
Johann Wojta ◽  
Astrid Fabry ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mast Cells ◽  
Umbilical Vein ◽  
Vascular Cells ◽  
Migratory Response ◽  
Thrombin Activation ◽  
Umbilical Vein Endothelial Cells ◽  
Primary Tissue ◽  
Local Expression

SummaryRecent data suggest that auricular thrombosis is associated with accumulation of mast cells (MC) in the upper endocardium (where usually no MC reside) and local expression of MGF (mast cell growth factor) (25). In this study, the role of vascular cells, thrombin-activation and MGF, in MC-migration was analyzed. For this purpose, cultured human auricular endocardial cells (HAUEC), umbilical vein endothelial cells (HUVEC) and uterine-(HUTMEC) and skin-derived (HSMEC) microvascular endothelial cells were exposed to thrombin or control medium, and the migration of primary tissue MC (lung, n = 6) and HMC-1 cells (human MC-line) against vascular cells (supernatants) measured. Supernatants (24 h) of unstimulated vascular cells (monolayers of endocardium or endothelium) as well as recombinant (rh) MGF induced a significant migratory response in HMC-1 (control: 3025 ± 344 cells [100 ± 11.4%] vs. MGF, 100 ng/ml: 8806 ± 1019 [291 ± 34%] vs. HAUEC: 9703 ± 1506 [320.8 ± 49.8%] vs. HUTMEC: 8950 ± 1857 [295.9 ± 61.4%] vs. HSMEC: 9965 ± 2018 [329.4 ± 66.7%] vs. HUVEC: 9487 ± 1402 [313.6 ± 46.4%], p <0.05) as well as in primary lung MC. Thrombin-activation (5 U/ml, 12 h) of vascular cells led to an augmentation of the directed migration of MC as well as to a hirudin-sensitive increase in MGF synthesis and release. Moreover, a blocking anti-MGF antibody was found to inhibit MC-migration induced by unstimulated or thrombin-activated vascular cells. Together, these data show that endocardial and other vascular cells can induce migration of human MC. This MC-chemotactic signal of the vasculature is associated with expression and release of MGF, augmentable by thrombin, and may play a role in the pathophysiology of (auricular) thrombosis.

Osteoporosis Entwined with Cardiovascular Disease: The Implication of Osteoprotegerin and Example of Statins

2020 ◽  
Vol 27 ◽  
Author(s):  
Maria V. Deligiorgi ◽  
Mihalis I. Panayiotidis ◽  
Gerasimos Siasos ◽  
Dimitrios T. Trafalis
Keyword(s):  
Cardiovascular Disease ◽  
Physicochemical Characteristics ◽  
Dual Role ◽  
Present Review ◽  
Vascular Cells ◽  
Molecular Fingerprint ◽  
Missing Link ◽  
Epidemiological Factors ◽  
Outstanding Issue

: Beyond being epiphenomenon of shared epidemiological factors, the integration of osteoporosis (OP) with cardiovascular disease (CVD)− termed "calcification paradox"− reflects a continuum of aberrant cardiometabolic status. The present review provides background knowledge on "calcification paradox", focusing on the endocrine aspect of vasculature orchestrated by the osteoblastic molecular fingerprint of vascular cells, acquired via imbalance among established modulators of mineralization. Osteoprotegerin (OPG)–the well-established osteoprotective cytokine−has recently been shown to exert a vessel-modifying role. Prompted by this notion, the present review interrogates OPG as the potential missing link between OP and CVD. However, so far, the confirmation of this hypothesis is hindered by the equivocal role of OPG in CVD, being both proatherosclerotic and antiatherosclerotic. Further research is needed to illuminate whether OPG could be biomarker of the "calcification paradox". Moreover, the present review brings into prominence the dual role of statins−cardioprotective and osteoprotective− as potential illustration of the integration of CVD with OP. Considering that the statins-induced modulation of OPG is central to the statins-driven osteoprotective signalling, statins could be suggested as illustration of the role of OPG in the bone/vessels crosstalk, if further studies consolidate the contribution of OPG to the cardioprotective role of statins. Another outstanding issue that merits further evaluation is the inconsistency of the osteoprotective role of statins. Further understanding of the varying bone-modifying role of statins, likely attributed to the unique profile of different classes of statins defined by distinct physicochemical characteristics, may yield tangible benefits for treating simultaneously OP and CVD.

scholarly journals Role of Matrix Gla Protein in the Complex Network of Coronary Artery Disease: A Comprehensive Review

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 737
Author(s):  
Marko Kumric ◽  
Josip A. Borovac ◽  
Tina Ticinovic Kurir ◽  
Dinko Martinovic ◽  
Ivan Frka Separovic ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Complex Network ◽  
Vascular Calcification ◽  
Vitamin K ◽  
Clinical Decision Making ◽  
Large Body ◽  
Matrix Gla Protein ◽  
Artery Disease

Coronary artery disease (CAD) is widely recognized as one of the most important clinical entities. In recent years, a large body of accumulated data suggest that coronary artery calcification, a process highly prevalent in patients with CAD, occurs via well-organized biologic processes, rather than passively, as previously regarded. Matrix Gla protein (MGP), a vitamin K-dependent protein, emerged as an important inhibitor of both intimal and medial vascular calcification. The functionality of MGP hinges on two post-translational modifications: phosphorylation and carboxylation. Depending on the above-noted modifications, various species of MGP may exist in circulation, each with their respective level of functionality. Emerging data suggest that dysfunctional species of MGP, markedly, dephosphorylated-uncarboxylated MGP, might find its application as biomarkers of microvascular health, and assist in clinical decision making with regard to initiation of vitamin K supplementation. Hence, in this review we summarized the current knowledge with respect to the role of MGP in the complex network of vascular calcification with concurrent inferences to CAD. In addition, we discussed the effects of warfarin use on MGP functionality, with concomitant implications to coronary plaque stability.

scholarly journals Microglia control small vessel calcification via TREM2

2021 ◽  
Vol 7 (9) ◽  
pp. eabc4898
Author(s):  
Yvette Zarb ◽  
Sucheta Sridhar ◽  
Sina Nassiri ◽  
Sebastian Guido Utz ◽  
Johanna Schaffenrath ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Vascular Calcification ◽  
Neurovascular Unit ◽  
Small Vessel ◽  
Vascular Pathology ◽  
Cns Development ◽  
Brain Calcification

Microglia participate in central nervous system (CNS) development and homeostasis and are often implicated in modulating disease processes. However, less is known about the role of microglia in the biology of the neurovascular unit (NVU). In particular, data are scant on whether microglia are involved in CNS vascular pathology. In this study, we use a mouse model of primary familial brain calcification, Pdgfbret/ret, to investigate the role of microglia in calcification of the NVU. We report that microglia enclosing vessel calcifications, coined calcification-associated microglia, display a distinct activation phenotype. Pharmacological ablation of microglia with the CSF1R inhibitor PLX5622 leads to aggravated vessel calcification. Mechanistically, we show that microglia require functional TREM2 for controlling vascular calcification. Our results demonstrate that microglial activity in the setting of pathological vascular calcification is beneficial. In addition, we identify a previously unrecognized function of microglia in halting the expansion of vascular calcification.

The role of genetics in fetal programming of adult cardiometabolic disease

2021 ◽  
pp. 1-8
Author(s):  
Carlos Sánchez-Soriano ◽  
Ewan R. Pearson ◽  
Rebecca M. Reynolds
Keyword(s):  
Cardiometabolic Disease ◽  
Genetic Determinants ◽  
Glucose And Lipid Metabolism ◽  
Developmental Growth ◽  
Genome Wide ◽  
Maternal Genotype ◽  
Disease Risks ◽  
Independent Effects ◽  
Meta Analyses

Abstract Disturbances affecting early development have broad repercussions on the individual’s health during infancy and adulthood. Multiple observational studies throughout the years have shown that alterations of fetal growth are associated with increased cardiometabolic disease risks. However, the genetic component of this association only started to be investigated in the last 40 years, when single genes with distinct effects were investigated. Birth weight (BW), commonly reported as the outcome of developmental growth, has been estimated to be 20% to 60% heritable. Through Genome-Wide Association (GWA) meta-analyses, 190 different loci have been identified being associated with BW, and while many of these loci designate genes involved in glucose and lipid metabolism, with clear ties to fetal development, the role of others is not yet understood. In addition, due to its influence over the intrauterine environment, the maternal genotype also plays an important part in the determination of offspring BW, with the same loci having independent effects of different magnitude or even direction. There is still much to uncover regarding the genetic determinants of BW and the interactions between maternal, offspring, and even paternal genotype. To fully understand these, diverse and novel cohorts from multiple ancestries collecting extensive neonatal phenotype will be needed. This review compiles, chronologically, the main findings in the investigation of the genetics of BW.

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

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1222
Author(s):  
Domitilla Mandatori ◽  
Letizia Pelusi ◽  
Valeria Schiavone ◽  
Caterina Pipino ◽  
Natalia Di Pietro ◽  
...  
Keyword(s):  
Bone Loss ◽  
Vascular Calcification ◽  
Vascular System ◽  
The Elderly ◽  
Food Supplement ◽  
Vitamin K2 ◽  
Bioactive Molecules ◽  
Calcium Deposition ◽  
Age Related

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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