scholarly journals Vascular Calcification: Key Roles of Phosphate and Pyrophosphate

2021 ◽  
Vol 22 (24) ◽  
pp. 13536
Author(s):  
Ricardo Villa-Bellosta
Keyword(s):  
Vascular Calcification ◽  
Current Knowledge ◽  
Genetic Diseases ◽  
Cardiovascular Complications ◽  
High Serum ◽  
Western Society ◽  
Phosphorus Concentration ◽  
Aortic Smooth Muscle ◽  
Atheroma Plaque

Cardiovascular complications due to accelerated arterial stiffening and atherosclerosis are the leading cause of morbimortality in Western society. Both pathologies are frequently associated with vascular calcification. Pathologic calcification of cardiovascular structures, or vascular calcification, is associated with several diseases (for example, genetic diseases, diabetes, and chronic kidney disease) and is a common consequence of aging. Calcium phosphate deposition, mainly in the form of hydroxyapatite, is the hallmark of vascular calcification and can occur in the medial layer of arteries (medial calcification), in the atheroma plaque (intimal calcification), and cardiac valves (heart valve calcification). Although various mechanisms have been proposed for the pathogenesis of vascular calcification, our understanding of the pathogenesis of calcification is far from complete. However, in recent years, some risk factors have been identified, including high serum phosphorus concentration (hyperphosphatemia) and defective synthesis of pyrophosphate (pyrophosphate deficiency). The balance between phosphate and pyrophosphate, strictly controlled by several genes, plays a key role in vascular calcification. This review summarizes the current knowledge concerning phosphate and pyrophosphate homeostasis, focusing on the role of extracellular pyrophosphate metabolism in aortic smooth muscle cells and macrophages.

scholarly journals Changes of tannin and nutrients during decomposition of branchlets of Casuarina equisetifolia plantation in subtropical coastal areas of China

2013 ◽  
Vol 59 (No. 2) ◽  
pp. 74-79 ◽  
Author(s):  
Zhang LH ◽  
Zhang SJ ◽  
Ye GF ◽  
Shao HB ◽  
Lin GH ◽  
...  
Keyword(s):  
Condensed Tannins ◽  
Total Phenolics ◽  
Current Knowledge ◽  
Dry Weight ◽  
Phosphorus Concentration ◽  
Casuarina Equisetifolia ◽  
Nitrogen And Phosphorus ◽  
Litterbag Experiment ◽  
Time Required

A litterbag experiment was conducted to investigate the changes of tannins and nutrients in branchlets at different decomposition stages of Casuarina equisetifolia in southern subtropical coastal zone, China, using the colorimetric assays. The time required for the loss of half of the initial dry weight (t<sub>50</sub>) was 9.13 months. Total phenolics (TP), extractable condensed tannins (ECT), protein-bound condensed tannins (PBCT), total condensed tannins (TCT) and protein precipitation capacity (PPC) of branchlets litter decreased rapidly, while fibre-bound condensed tannins (FBCT) increased during decomposition. Nitrogen and phosphorus concentration of the branchlet litter both increased gradually during decay. Negative correlations between TP and nitrogen or phosphorus, as well as TCT and nitrogen or phosphorus were found. These chemical changes enhanced the current knowledge on the potential ecological role of nutrient transformation in tannins in C. equisetifolia plantations.

The role of bone metabolism regulators sclerotin and osteoprotegerin in the development of cardiovascular complications in the late stages of chronic kidney disease

2021 ◽  
Vol 25 (6) ◽  
pp. 63-70
Author(s):  
F. U. Dzgoeva ◽  
O. V. Remizov ◽  
V. Kh. Botsieva ◽  
N. G. Malakhova ◽  
Z. R. Ikoeva ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Blood Serum ◽  
Bone Metabolism ◽  
Vascular Calcification ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Enzyme Linked Immunosorbent Assay ◽  
Commercial Kits

BACKGROUND. Cardiovascular complications caused by vascular calcification in chronic kidney disease (CKD) are closely related to disorders of bone and mineral metabolism, the mechanisms of which require further study.THE AIM: to clarify the role of the regulatory proteins of bone metabolism of sclerostin and osteoprotegerin in the processes of vascular calcification and the development of cardiovascular complications in CKD.PATIENTS AND METHODS. 110 patients with stage 3-5D CKD (67 men) were examined. Median age is 47.0 (23.0-68.0) years. Osteoprotegerin (OPG), sclerostin, intact parathyroid hormone (IPTG), troponin I in blood serum were determined using commercial kits "Enzyme-linked Immunosorbent Assay Kit for Sclerostin" ("Cloud-Clone Corp.", USA) and commercial kits "ELISA kit" ("Biomedica" (Austria) by enzyme immunoassay (ELISA). Echocardiography with Dopplerography was performed on the device "ALOKA 4000" ("Toshiba", Japan). The left ventricular myocardial mass index (LVMI) and peak systolic blood flow velocity in the aortic arch (Vps, peak systolic velocity) were determined to quantify hemodynamic changes indirectly indicating the state of the aortic vascular wall.RESULTS. Analysis of the ratios of the calculated glomerular filtration rate (EGFR), IMLJ, Vps, OPG, and sclerostin showed that a decrease in excretory kidney function is accompanied by an increase in the concentrations of OPG and sclerostin in the blood serum. At the same time, there is an increase in IMLJ and Vps. During the correlation analysis, it was shown that the level of OPG was positively correlated with the level of sclerostin and negatively with the level of iPTG.CONCLUSION. In our study, we obtained data confirming the interactive interaction between the vascular and bone systems. Morphogenetic proteins-inhibitors of bone metabolism (sclerostin and OPG) play a significant role in the defeat of the cardiovascular system in patients with CKD, as they promotes the development of vascular calcification.

scholarly journals Tissue Non-Specific Alkaline Phosphatase and Vascular Calcification: A Potential Therapeutic Target

2019 ◽  
Vol 15 (2) ◽  
pp. 91-95 ◽  
Author(s):  
Daniel Azpiazu ◽  
Sergio Gonzalo ◽  
Ricardo Villa-Bellosta
Keyword(s):  
Alkaline Phosphatase ◽  
Vascular Calcification ◽  
Current Knowledge ◽  
Crystal Deposition ◽  
New Agents ◽  
Vascular Walls ◽  
Nucleotide Pyrophosphatase ◽  
The Subject ◽  
Hydroxyapatite Crystals

Vascular calcification is a pathologic phenomenon consisting of calcium phosphate crystal deposition in the vascular walls. Vascular calcification has been found to be a risk factor for cardiovascular diseases, due to its correlation with cardiovascular events and mortality, and it has been associated with aging, diabetes, and chronic kidney disease. </P><P> Studies of vascular calcification have focused on phosphate homeostasis, primarily on the important role of hyperphosphatemia. Moreover, vascular calcification has been associated with loss of plasma pyrophosphate, one of the main inhibitors of calcification, thus indicating the importance of the phosphate/pyrophosphate ratio. </P><P> Extracellular pyrophosphate can be synthesized from extracellular ATP by ecto-nucleotide pyrophosphatase/ phosphodiesterase, whereas pyrophosphate is hydrolyzed to phosphate by tissuenonspecific alkaline phosphatase, contributing to the formation of hydroxyapatite crystals. </P><P> Over the last decade, vascular calcification has been the subject of numerous reviews and studies, which have revealed new agents and activities that may aid in explaining the complex physiology of this condition. This review summarizes current knowledge about alkaline phosphatase and its role in the process of vascular calcification as a key regulator of the phosphate/pyrophosphate ratio.

scholarly journals Vascular Calcification in Chronic Kidney Disease: The Role of Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Kerstin Benz ◽  
Karl-Friedrich Hilgers ◽  
Christoph Daniel ◽  
Kerstin Amann
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Risk Groups ◽  
Cardiovascular Complications ◽  
Atherosclerotic Plaques ◽  
Cardiovascular Morbidity And Mortality ◽  
Functional Factors ◽  
Age And Sex

Cardiovascular complications are extremely frequent in patients with chronic kidney disease (CKD) and death from cardiac causes is the most common cause of death in this particular population. Cardiovascular disease is approximately 3 times more frequent in patients with CKD than in other known cardiovascular risk groups and cardiovascular mortality is approximately 10-fold more frequent in patients on dialysis compared to the age- and sex-matched segments of the nonrenal population. Among other structural and functional factors advanced calcification of atherosclerotic plaques as well as of the arterial and venous media has been described as potentially relevant for this high cardiovascular morbidity and mortality. One potential explanation for this exceedingly high vascular calcification in animal models as well as in patients with CKD increased systemic and most importantly local (micro)inflammation that has been shown to favor the development of calcifying particles by multiple ways. Of note, local vascular upregulation of proinflammatory and proosteogenic molecules is already present at early stages of CKD and may thus be operative for vascular calcification. In addition, increased expression of costimulatory molecules and mast cells has also been documented in patients with CKD pointing to a more inflammatory and potentially less stable phenotype of coronary atherosclerotic plaques in CKD.

scholarly journals P0876THE ROLE OF TRPM7 IN VASCULAR CALCIFICATION: COMPARISION BETWEEN PHOSPHATE AND UREMIC TOXIN

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Chien-Te Lee ◽  
Hwee-Yeong Ng
Keyword(s):  
Smooth Muscle ◽  
Vascular Calcification ◽  
Uremic Toxin ◽  
Alizarin Red ◽  
Aortic Smooth Muscle ◽  
Calcium Sensing ◽  
Phenotypic Transformation ◽  
Indoxyl Sulphate ◽  
Phosphate Treatment

Abstract Background and Aims Vascular calcification is a common complication in patients with chronic kidney disease (CKD) and associated with increased morbidity and mortality. Pathogenesis of vascular calcification in CKD is multiple and phenotypic transformation of vascular smooth muscle cell (VSMC) is of critical importance. TRPM7 is a magnesium channel that regulate magnesium transport. The role of TRPM7 in VSMC transformation during vascular calcification is not clear. We aim to investigate the effects of phosphate and indoxyl sulphate on the expression of TRPM7 in VSMC and 2-APB, the TRPM7 blocker was used to evaluate the alteration of calcification-related molecules. Method Human aortic smooth muscle cells (HASMC) were used and treated either with phosphate (3.3mM) or indoxyl sulphate (500uM) for 7 days. 2-APB, a channel blocker of TRPM7 was added simultaneously in blocking experiment. Cells were then examined grossly and alizarin red solution was employed for calcification staining assessment. For calcification process study, cells were harvested for gene expression and protein abundance analysis. Results Gross examination did not find evidence of cell death during experiment on both treatments. Alizarin staining revealed apparent calcification in phosphate-treated HASMC but it was unremarkable in indoxyl sulphate. Phosphate treatment induced significant increase in RUNX2(151±35.8% of control), BMP2(124±10.1%), BMP7(155±9.3%), vitamin D receptor (VDR, 138±21%), calcium sensing receptor (CaSR, 185± 39%) and TRPM7(172±33.7%, all p&lt; 0.05), but DKK1 and sclerostin were not changed. The addition of 2-APB prevented the increase of RUNX2(107±31.2%), BMP2(80±4.9%), BMP7(72±32.9%), VDR (94±43.2%), CaSR (83±17%) and TRPM7(118±23.9%). Indoxyl sulphate treatment was associated with decrease in TRPM7 (45±22%, p&lt;0.05), but increase in BMP2(136±10.4%), VDR (154±53.5%) were noted. There were no significant alterations in CaSR (108±43.7%) and sclerostin (110±27.1%). Co-administration with 2-APB partially reduced the increase in RUNX2(158±55.1%), VDR (149±35.9%). The abundance of BMP2/7were not changed. TRPM7 was decreased significantly (33±23.1%). Conclusion We concluded that both phosphate and indoxyl sulphate induced calcification in VSMC but it was less in indoxyl sulphate. TRPM7 was upregulated by phosphate but decreased in indoxyl sulphate treatment. Blocking TRPM7 with 2-APB can prevent phosphate-induced calcification but partially attenuated calcification during indoxyl sulphate administration.

Circulating uromodulin inhibits vascular calcification by interfering with pro-inflammatory cytokine signalling

2020 ◽  
Author(s):  
Ioana Alesutan ◽  
Trang T D Luong ◽  
Nadeshda Schelski ◽  
Jaber Masyout ◽  
Susanne Hille ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Serum Levels ◽  
Vascular Pathology ◽  
Adeno Associated Virus ◽  
Aortic Smooth Muscle ◽  
Key Factor ◽  
Factor Α

Abstract Aims Uromodulin is produced exclusively in the kidney and secreted into both urine and blood. Serum levels of uromodulin are correlated with kidney function and reduced in chronic kidney disease (CKD) patients, but physiological functions of serum uromodulin are still elusive. This study investigated the role of uromodulin in medial vascular calcification, a key factor associated with cardiovascular events and mortality in CKD patients. Methods and results Experiments were performed in primary human (HAoSMCs) and mouse (MOVAS) aortic smooth muscle cells, cholecalciferol overload and subtotal nephrectomy mouse models and serum from CKD patients. In three independent cohorts of CKD patients, serum uromodulin concentrations were inversely correlated with serum calcification propensity. Uromodulin supplementation reduced phosphate-induced osteo-/chondrogenic transdifferentiation and calcification of HAoSMCs. In human serum, pro-inflammatory cytokines tumour necrosis factor α (TNFα) and interleukin-1β (IL-1β) co-immunoprecipitated with uromodulin. Uromodulin inhibited TNFα and IL-1β-induced osteo-/chondrogenic signalling and activation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated β cells (NF-kB) as well as phosphate-induced NF-kB-dependent transcriptional activity in HAoSMCs. In vivo, adeno-associated virus (AAV)-mediated overexpression of uromodulin ameliorated vascular calcification in mice with cholecalciferol overload. Conversely, cholecalciferol overload-induced vascular calcification was aggravated in uromodulin-deficient mice. In contrast, uromodulin overexpression failed to reduce vascular calcification during renal failure in mice. Carbamylated uromodulin was detected in serum of CKD patients and uromodulin carbamylation inhibited its anti-calcific properties in vitro. Conclusions Uromodulin counteracts vascular osteo-/chondrogenic transdifferentiation and calcification, at least in part, through interference with cytokine-dependent pro-calcific signalling. In CKD, reduction and carbamylation of uromodulin may contribute to vascular pathology.

scholarly journals Cardiac Remodeling in Obesity

2008 ◽  
Vol 88 (2) ◽  
pp. 389-419 ◽  
Author(s):  
E. Dale Abel ◽  
Sheldon E. Litwin ◽  
Gary Sweeney
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling ◽  
Current Knowledge ◽  
Strong Association ◽  
Obesity Paradox ◽  
Cardiovascular Complications ◽  
Structure And Function ◽  
Model Studies ◽  
And Function

The dramatic increase in the prevalence of obesity and its strong association with cardiovascular disease have resulted in unprecedented interest in understanding the effects of obesity on the cardiovascular system. A consistent, but puzzling clinical observation is that obesity confers an increased susceptibility to the development of cardiac disease, while at the same time affording protection against subsequent mortality (termed the obesity paradox). In this review we focus on evidence available from human and animal model studies and summarize the ways in which obesity can influence structure and function of the heart. We also review current hypotheses regarding mechanisms linking obesity and various aspects of cardiac remodeling. There is currently great interest in the role of adipokines, factors secreted from adipose tissue, and their role in the numerous cardiovascular complications of obesity. Here we focus on the role of leptin and the emerging promise of adiponectin as a cardioprotective agent. The challenge of understanding the association between obesity and heart failure is complicated by the multifaceted interplay between various hemodynamic, metabolic, and other physiological factors that ultimately impact the myocardium. Furthermore, the end result of obesity-associated changes in the myocardial structure and function may vary at distinct stages in the progression of remodeling, may depend on the individual pathophysiology of heart failure, and may even remain undetected for decades before clinical manifestation. Here we summarize our current knowledge of this complex yet intriguing topic.

scholarly journals Vascular Calcification Mechanisms: Updates and Renewed Insight into Signaling Pathways Involved in High Phosphate-Mediated Vascular Smooth Muscle Cell Calcification

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 804
Author(s):  
Nima Abbasian
Keyword(s):  
Dna Damage ◽  
Smooth Muscle ◽  
Intracellular Calcium ◽  
Vascular Calcification ◽  
Oxidative Dna Damage ◽  
Current Knowledge ◽  
High Serum ◽  
Renal Diseases ◽  
Future Research ◽  
Vascular Smcs

Vascular calcification (VC) is associated with aging, cardiovascular and renal diseases and results in poor morbidity and increased mortality. VC occurs in patients with chronic kidney disease (CKD), a condition that is associated with high serum phosphate (Pi) and severe cardiovascular consequences. High serum Pi level is related to some pathologies which affect the behaviour of vascular cells, including platelets, endothelial cells (ECs) and smooth muscle cells (SMCs), and plays a central role in promoting VC. VC is a complex, active and cell-mediated process involving the transdifferentiation of vascular SMCs to a bone-like phenotype, systemic inflammation, decreased anti-calcific events (loss of calcification inhibitors), loss in SMC lineage markers and enhanced pro-calcific microRNAs (miRs), an increased intracellular calcium level, apoptosis, aberrant DNA damage response (DDR) and senescence of vascular SMCs. This review gives a brief overview of the current knowledge of VC mechanisms with a particular focus on Pi-induced changes in the vascular wall important in promoting calcification. In addition to reviewing the main findings, this review also sheds light on directions for future research in this area and discusses emerging pathways such as Pi-regulated intracellular calcium signaling, epigenetics, oxidative DNA damage and senescence-mediated mechanisms that may play critical, yet to be explored, regulatory and druggable roles in limiting VC.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

Prospective Memory Development Across the Lifespan

2020 ◽  
Vol 25 (3) ◽  
pp. 162-173 ◽  
Author(s):  
Sascha Zuber ◽  
Matthias Kliegel
Keyword(s):  
Prospective Memory ◽  
Healthy Aging ◽  
Present Model ◽  
Current Knowledge ◽  
Well Being ◽  
The Elderly ◽  
Cognitive Factors ◽  
Everyday Functioning ◽  
Integrative Framework

Abstract. Prospective Memory (PM; i.e., the ability to remember to perform planned tasks) represents a key proxy of healthy aging, as it relates to older adults’ everyday functioning, autonomy, and personal well-being. The current review illustrates how PM performance develops across the lifespan and how multiple cognitive and non-cognitive factors influence this trajectory. Further, a new, integrative framework is presented, detailing how those processes interplay in retrieving and executing delayed intentions. Specifically, while most previous models have focused on memory processes, the present model focuses on the role of executive functioning in PM and its development across the lifespan. Finally, a practical outlook is presented, suggesting how the current knowledge can be applied in geriatrics and geropsychology to promote healthy aging by maintaining prospective abilities in the elderly.

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