Association of vascular fluoride uptake with vascular calcification and coronary artery disease

2012 ◽  
Vol 33 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Yuxin Li ◽  
Gholam R. Berenji ◽  
Wisam F. Shaba ◽  
Bashir Tafti ◽  
Ella Yevdayev ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Vascular Calcification ◽  
Fluoride Uptake ◽  
Artery Disease

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.

Abstract 426: Overexpression of Tissue-nonspecific Alkaline Phosphatase (TNAP) Accelerates Coronary Artery Disease in the Setting of Hypercholesterolemia in Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Filippo Romanelli ◽  
AnthonyMarco Corbo ◽  
Maryam Salehi ◽  
Manisha C Yadav ◽  
Soha Salman ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Alkaline Phosphatase ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Vascular Calcification ◽  
Coronary Atherosclerosis ◽  
Atherogenic Diet ◽  
Arterial Calcification ◽  
Tissue Nonspecific Alkaline Phosphatase ◽  
Artery Disease

Objective: Vascular calcification in asymptomatic individuals is an independent predictor of coronary heart disease (CHD). It is therefore plausible that vascular calcification plays a direct pathophysiological role in atherosclerosis, an underlying cause of CHD. The purpose of this study was to examine the contribution that vascular calcification has on the development of coronary atherosclerosis in a mouse model of familial hypercholesterolemia. Approach and Results: Calcification was induced by overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells of mice harboring a point mutation in the low density lipoprotein receptor ( ldlr, wicked high cholesterol, WHC). Mice were fed an atherogenic diet; echocardiographic and biochemical data were collected longitudinally. Atherosclerosis and vascular calcification were analyzed histologically in the aorta, aortic sinus and coronary arteries. TNAP mice were also treated with a combination of an atherogenic diet and a specific inhibitor of TNAP (SBI-425). Combined with the ldlr mutation and an atherogenic diet, TNAP-driven arterial calcification led to severe atherosclerosis with 100% morbidity characterized by occlusive coronary artery disease, pathological cardiac hypertrophy with dilated LV and reduced ejection fraction (EF). We detected an interaction between vascular calcification and atherosclerosis in mice with endothelial TNAP overexpression. This interaction was particularly prominent in coronary circulation. Targeting TNAP activity therapeutically helped improve survival and heart function of endothelial TNAP overexpressor mice, however the incomplete inhibition of TNAP by SBI-425 was a limitation of this study. Conclusions: Vascular calcification via TNAP overexpression in endothelial cells promotes coronary atherosclerosis and is pathogenic under conditions of hypercholesterolemia.

scholarly journals Compositional change of gut microbiome and osteocalcin expressing endothelial progenitor cells in patients with coronary artery disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249187
Author(s):  
Takumi Toya ◽  
Ilke Ozcan ◽  
Michel T. Corban ◽  
Jaskanwal D. Sara ◽  
Eric V. Marietta ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Vascular Calcification ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Endothelial Progenitor ◽  
Artery Disease ◽  
Circulating Levels

Osteogenic endothelial progenitor cells (EPCs) contribute to impaired endothelial repair and promote coronary artery disease (CAD) and vascular calcification. Immature EPCs expressing osteocalcin (OCN) has been linked to unstable CAD; however, phenotypic regulation of OCN-expressing EPCs is not understood. We hypothesized that gut-microbiome derived pro-inflammatory substance, trimethylamine N-oxide (TMAO) might be associated with mobilization of OCN-expressing EPCs. This study aimed to investigate the association between dysbiosis, TMAO, and circulating mature and immature OCN-expressing EPCs levels in patients with and without CAD. We included 202 patients (CAD N = 88; no CAD N = 114) who underwent assessment of EPCs using flow cytometry and gut microbiome composition. Mature and immature EPCs co-staining for OCN were identified using cell surface markers as CD34+/CD133-/kinase insert domain receptor (KDR)+ and CD34-/CD133+/KDR+ cells, respectively. The number of observed operational taxonomy units (OTU), index of microbial richness, was used to identify patients with dysbiosis. The number of immature OCN-expressing EPCs were higher in patients with CAD or dysbiosis than patients without. TMAO levels were not associated with circulating levels of OCN-expressing EPCs. The relative abundance of Ruminococcus gnavus was moderately correlated with circulating levels of immature OCN-expressing EPCs, especially in diabetic patients. Gut dysbiosis was associated with increased levels of TMAO, immature OCN-expressing EPCs, and CAD. The relative abundance of Ruminococcus gnavus was correlated with immature OCN-expressing EPCs, suggesting that the harmful effects of immature OCN-expressing EPCs on CAD and potentially vascular calcification might be mediated by gut microbiome-derived systemic inflammation.

scholarly journals Relationships between the expression of adipocytokine genes and the calcification of coronary arteries in patients with coronary artery disease

2021 ◽  
Vol 36 (3) ◽  
pp. 68-77
Author(s):  
O. V. Gruzdeva ◽  
E. V. Belik ◽  
Yu. A. Dyleva ◽  
N. K. Brel ◽  
A. N. Kokov ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Real Time ◽  
Vascular Calcification ◽  
Artery Bypass ◽  
Biologically Active ◽  
Enzyme Linked Immunosorbent Assay ◽  
Perivascular Adipose Tissue ◽  
Artery Disease

Dysfunctional changes and remodeling of adipose tissue (АT) are associated with the formation of microcalcifications in the vascular wall. Biologically active substances synthesized by АT (adipocytokines) can act as promoters and inhibitors  of vascular calcification development. The few available experimental and clinical studies do not fully explain the possible mechanisms of these effects.Aim. To study the relationships between the adipocytokine profiles of adipocytes in epicardial and perivascular AT with the severity of coronary artery calcification in patients with coronary artery disease (CAD).Material and Methods. A total of 125 patients with CAD aged 59 (53; 66) years were examined. The isolated adipocytes of subcutaneous adipose tissue (SAT), epicardial adipose tissue (EAT), and perivascular adipose tissue (PVAT), obtained during coronary artery bypass grafting, were used to determine gene expression and secretion of adipocytokines (adiponectin, leptin, and IL-6). Expression of adipocytokine genes was assessed using quantitative PCR with detection of products in real time (real-time qPCR); the concentration of adipocytokines in the culture medium was determined by enzyme-linked immunosorbent assay using R&D Systems kits (Canada). Coronary artery (CA) calcification degree was assessed by multislice spiral computed tomography (MSCT) method. The calcium index of CA was determined by the Agatston method using the Syngo Calcium Scoring software package (Siemens AG Medical Solution, Germany).Results. Massive coronary calcification (CC) had the highest prevalence (58.8%) in patients with CAD. The highest level of expression of the ADIPOQ gene in all types of fat stores was observed in patients with moderate/medium CС compared to those with massive CС; the maximum expression of ADIPOQ was observed in the culture of PVAT adipocytes. Expression of the LEP and IL6 genes in massive CC was higher, with the maximum values in the culture of EAT adipocytes relative to SAT and PVAT adipocytes. Decreases in the levels of ADIPOQ mRNA and its secretion, increases in the levels of mRNA of LEP and IL6 and their secretion in adipocytes of the EAT and PVAT were associated with the development of СС in patients with CAD.Conclusion. Proinflammatory adipokines produced by adipocytes of patients with CAD during hypoxia induced vascular calcification by stimulating oxidative stress, osteoblast differentiation, apoptosis, and proliferation of smooth muscle cells. Endothelial cells, when stimulated with proinflammatory adipocytokines, tended to transform into osteoblasts, which further aggravated the degree of vascular inflammation and calcification.

scholarly journals Predictors of 18F-sodium fluoride uptake in patients with stable coronary artery disease and adverse plaque features on computed tomography angiography

2019 ◽  
Vol 21 (1) ◽  
pp. 58-66 ◽  
Author(s):  
Jacek Kwiecinski ◽  
Damini Dey ◽  
Sebastien Cadet ◽  
Sang-Eun Lee ◽  
Balaji Tamarappoo ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
High Risk ◽  
Sodium Fluoride ◽  
Computed Tomography Angiography ◽  
Stable Coronary Artery Disease ◽  
Qualitative And Quantitative ◽  
Fluoride Uptake ◽  
Artery Disease

Abstract Aims In patients with stable coronary artery disease (CAD) and high-risk plaques (HRPs) on coronary computed tomography angiography (CTA), we sought to define qualitative and quantitative CTA predictors of abnormal coronary 18F-sodium fluoride uptake (18F-NaF) by positron emission tomography (PET). Methods and results Patients undergoing coronary CTA were screened for HRP. Those who presented with ≥3 CTA adverse plaque features (APFs) including positive remodelling; low attenuation plaque (LAP, <30 HU), spotty calcification; obstructive coronary stenosis ≥50%; plaque volume >100 mm3 were recruited for 18F-NaF PET. In lesions with stenosis ≥25%, quantitative plaque analysis and maximum 18F-NaF target to background ratios (TBRs) were measured. Of 55 patients, 35 (64%) manifested coronary 18F-NaF uptake. Of 68 high-risk lesions 49 (70%) had increased PET tracer activity. Of the APFs, LAP had the highest sensitivity (39.4%) and specificity (98.3%) for predicting 18F-NaF uptake. TBR values were higher in lesions with LAP compared to those without [1.6 (1.3–1.8) vs. 1.1 (1.0–1.3), P = 0.01]. On adjusted multivariable regression analysis, LAP (both qualitative and quantitative) was independently associated with plaque TBR [LAP qualitative: β = 0.47, 95% confidence interval (CI) 0.30–0.65; P < 0.001] and (LAP volume: β = 0.20 per 10 mm3, 95% CI 0.13–0.27; P < 0.001). Conclusion In stable CAD patients with HRP, LAP is predictive of 18F-NaF coronary uptake, but 18F-NaF is often seen in the absence of LAP. If 18F-NaF uptake is shown to be associated with adverse outcomes and becomes clinically used, the presence of LAP may define patients who would not benefit from the added testing.

scholarly journals Coronary 18F-Sodium Fluoride Uptake Predicts Outcomes in Patients With Coronary Artery Disease

2020 ◽  
Vol 75 (24) ◽  
pp. 3061-3074 ◽  
Author(s):  
Jacek Kwiecinski ◽  
Evangelos Tzolos ◽  
Philip D. Adamson ◽  
Sebastien Cadet ◽  
Alastair J. Moss ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Sodium Fluoride ◽  
Fluoride Uptake ◽  
Artery Disease
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