scholarly journals Cardiovascular disease and osteoporosis: is there a link between lipids and bone?

2002 ◽  
Vol 39 (3) ◽  
pp. 203-210 ◽  
Author(s):  
John R Burnett ◽  
Samuel D Vasikaran
Keyword(s):  
Cardiovascular Disease ◽  
Bone Density ◽  
Vascular Calcification ◽  
Cholesterol Biosynthesis ◽  
Hormone Replacement ◽  
Plasma Lipid ◽  
Clinical Effects ◽  
Cardiovascular Morbidity And Mortality ◽  
The Relationship

Atherosclerotic heart disease and osteoporosis are both diseases of old age. Evidence is accumulating for a link between vascular and bone disease. Calcification is a common feature of atherosclerotic plaques, and osteoporosis is associated with both atherosclerosis and vascular calcification. However, the relationship of vascular calcification to the pathogenesis of atherosclerosis remains incompletely understood. Hormone replacement therapy has beneficial effects in the prevention of both atherosclerosis and osteoporosis. Bisphosphonates inhibit bone resorption and are used in the treatment of osteoporosis, whereas the statins inhibit cholesterol biosynthesis and are used for the treatment of atherosclerosis. We have reviewed recent advances in the knowledge of the actions of bisphosphonates and statins at the cellular, molecular and end-organ levels in order to examine the relationship between cardiovascular disease and osteoporosis and to explore the link between lipids and bones. These studies suggest that the mechanism of actions of these two classes of drugs at the cellular level may not be mutually exclusive. There are some early clinical data to complement these findings, suggesting that statins increase bone density and bisphosphonates may have a beneficial effect in vivo on plasma lipid levels and on the atherosclerotic process. Properly designed prospective studies that examine the effect of statins on bone density and fractures, as well as the effects of bisphosphonates on lipid profiles, atherosclerotic progression and cardiovascular morbidity and mortality are needed to define clearly the clinical effects and potential new roles for these agents.

scholarly journals Inhibition of Gastrin-Releasing Peptide Attenuates Phosphate-Induced Vascular Calcification

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 737 ◽  
Author(s):  
Hyun-Joo Park ◽  
Yeon Kim ◽  
Mi-Kyoung Kim ◽  
Jae Joon Hwang ◽  
Hyung Joon Kim ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Vascular System ◽  
Ex Vivo ◽  
Calcium Deposition ◽  
Gastrin Releasing Peptide ◽  
Cardiovascular Morbidity And Mortality ◽  
Potential Strategy ◽  
Grp Receptor

Vascular calcification is the pathological deposition of calcium/phosphate in the vascular system and is closely associated with cardiovascular morbidity and mortality. Here, we investigated the role of gastrin-releasing peptide (GRP) in phosphate-induced vascular calcification and its potential regulatory mechanism. We found that the silencing of GRP gene and treatment with the GRP receptor antagonist, RC-3095, attenuated the inorganic phosphate-induced calcification of vascular smooth muscle cells (VSMCs). This attenuation was caused by inhibiting phenotype change, apoptosis and matrix vesicle release in VSMCs. Moreover, the treatment with RC-3095 effectively ameliorated phosphate-induced calcium deposition in rat aortas ex vivo and aortas of chronic kidney disease in mice in vivo. Therefore, the regulation of the GRP-GRP receptor axis may be a potential strategy for treatment of diseases associated with excessive vascular calcification.

scholarly journals Pharmacological and Nutritional Modulation of Vascular Calcification

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 100 ◽  
Author(s):  
Liv M. Vossen ◽  
Abraham A. Kroon ◽  
Leon J. Schurgers ◽  
Peter W. de Leeuw
Keyword(s):  
Cardiovascular Disease ◽  
Drug Therapy ◽  
Vascular Calcification ◽  
Vitamin K ◽  
Vascular Function ◽  
Clinical Importance ◽  
Arterial Calcification ◽  
Channel Blockers ◽  
Cardiovascular Morbidity And Mortality ◽  
Prevention And Treatment

Vascular calcification is an independent predictor of cardiovascular disease, and therefore, inhibition or regression of this processes is of clinical importance. The standard care regarding prevention and treatment of cardiovascular disease at this moment mainly depends on drug therapy. In animal and preclinical studies, various forms of cardiovascular drug therapy seem to have a positive effect on vascular calcification. In particular, calcium channel blockers and inhibitors of the renin–angiotensin–aldosteron system slowed down arterial calcification in experimental animals. In humans, the results of trials with these drugs are far less pronounced and often contradictory. There is limited evidence that the development of new atherosclerotic lesions may be retarded in patients with coronary artery disease, but existing lesions can hardly be influenced. Although statin therapy has a proven role in the prevention and treatment of cardiovascular morbidity and mortality, it is associated with both regression and acceleration of the vascular calcification process. Recently, nutritional supplements have been recognized as a potential tool to reduce calcification. This is particularly true for vitamin K, which acts as an inhibitor of vascular calcification. In addition to vitamin K, other dietary supplements may also modulate vascular function. In this narrative review, we discuss the current state of knowledge regarding the pharmacological and nutritional possibilities to prevent the development and progression of vascular calcification.

Abstract 641: Hypotrophic Vascular Remodeling Associates With Vascular Calcification in vivo in Vitamin D 3 -stimulated Leptin-deficient ob/ob Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Luciana S Carmo ◽  
Youri E Almeida ◽  
Marcel Liberman
Keyword(s):  
Cardiovascular Disease ◽  
Vitamin D ◽  
Vascular Calcification ◽  
Wall Thickness ◽  
Vascular Remodeling ◽  
Aortic Wall ◽  
Wall Area ◽  
Aortic Wall Thickness ◽  
Vitamin D 3

Vascular calcification may determine arterial flow imbalance through increasing vascular rigidity and Windkessel effect, frequently occurring in diabetes. Vascular remodeling, considered an adaptive response of the vessel to specific stimuli, may associate with calcification and participate in pathophysiology of cardiovascular disease. In order to further investigate the intersection between pathophysiology of vascular calcification and vascular remodeling, we hypothesized that leptin-deficient ob/ob mice, demonstrate increased vascular remodeling and vascular calcifying response to Vitamin D 3 in vivo compared to C57BL/6 (C57) mice. We injected C57 and ob/ob mice with Vitamin D 3 8x10 4 IU (VitD) daily or saline 0.9% ip. (Cont) for 14 days and for 21 days. Results are showed as Mean±SEM. We considered statistically significant if p<.05 after ANOVA (Newman-Keuls). After 14d, o b/ob VitD aorta decreased aortic wall thickness (24.3±0.4μm) versus ob/ob Cont (29.7±1.3μm), vs. C57VitD (34.4±0.6μm) and vs. C57Cont (39±1.3μm), p<.05 n=6. After 21d, we also showed that ob/ob VitD decreased aortic wall thickness (25.4±0.5μm) vs. ob/ob Cont (29.7±1.3μm) and vs. C57Cont (39.0±1.3μm), p<.05 n=3. Moreover, o b/ob VitD decreased vessel wall area (VWA)= 79120±3957μm 2 vs. ob/ob Cont=85310±4593μm 2 and vs. C57Cont=96970±6719μm 2 after 14d (n=6) and also after 21d ( ob/ob VitD=72090±3268μm 2 vs. ob/ob Cont=85310±4593μm 2 (n=3). On contrary, C57VitD did not change VWA. Coincidently, ob/ob VitD increased vascular calcification after 14d (total Ca ++ area burden=4548.2μm 2 , n=6) and after 21d (total Ca ++ area burden=2212.88 μm 2 , n=3) respectively. C57VitD and C57Cont did not calcify (n=6). Together with increased VWA loss and calcification, ob/ob VitD also showed augmented elastolysis and fibrosis. Nevertheless, hypotrophic remodeling did not determine any change in vascular lumen area ( ob/ob VitD=208300±24810μm 2 ; ob/ob Cont=207300±22740μm 2 , C57VitD=196800±22120μm 2 and C57Cont=225400±17960μm 2 ) after 14d in this model. Vascular remodeling associated with calcification and other architectural changes of the vascular wall may bring important insights for investigating human cardiovascular disease in obese and insulin resistant background.

scholarly journals X-ray Micro-Computed Tomography: An Emerging Technology to Analyze Vascular Calcification in Animal Models

2020 ◽  
Vol 21 (12) ◽  
pp. 4538
Author(s):  
Samantha J. Borland ◽  
Julia Behnsen ◽  
Nick Ashton ◽  
Sheila E. Francis ◽  
Keith Brennan ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Animal Models ◽  
Vascular Calcification ◽  
Micro Computed Tomography ◽  
Mineralized Tissue ◽  
X Ray ◽  
Cardiovascular Morbidity And Mortality ◽  
Non Destructive ◽  
Preparation Techniques

Vascular calcification describes the formation of mineralized tissue within the blood vessel wall, and it is highly associated with increased cardiovascular morbidity and mortality in patients with chronic kidney disease, diabetes, and atherosclerosis. In this article, we briefly review different rodent models used to study vascular calcification in vivo, and critically assess the strengths and weaknesses of the current techniques used to analyze and quantify calcification in these models, namely 2-D histology and the o-cresolphthalein assay. In light of this, we examine X-ray micro-computed tomography (µCT) as an emerging complementary tool for the analysis of vascular calcification in animal models. We demonstrate that this non-destructive technique allows us to simultaneously quantify and localize calcification in an intact vessel in 3-D, and we consider recent advances in µCT sample preparation techniques. This review also discusses the potential to combine 3-D µCT analyses with subsequent 2-D histological, immunohistochemical, and proteomic approaches in correlative microscopy workflows to obtain rich, multifaceted information on calcification volume, calcification load, and signaling mechanisms from within the same arterial segment. In conclusion we briefly discuss the potential use of µCT to visualize and measure vascular calcification in vivo in real-time.

scholarly journals In Vivo Calcium and Phosphate Iontophoresis for the Topical Treatment of Osteoporosis

2012 ◽  
Vol 92 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Izabella Gomez ◽  
Andrea Szabó ◽  
Lajos Pap ◽  
Lajos Pap ◽  
Krisztina Boda ◽  
...  
Keyword(s):  
Bone Density ◽  
Hormone Replacement ◽  
Estrogen Therapy ◽  
Biomechanical Properties ◽  
Sprague Dawley ◽  
In Vivo Experiments ◽  
17Β Estradiol ◽  
Biomechanical Features ◽  
And Control

Background In addition to systemic treatment, osteoporosis may be treated topically by incorporating calcium and phosphate into the bone. Objective This article describes the use of a recently developed, novel iontophoretic apparatus suitable for local ion delivery into bones. In this study, in vivo experiments were performed to compare the effects of local electrotherapy and those of systemic hormone replacement on bone. Design In this study, local iontophoresis was carried out in ovariectomized and control rats. Bone density, biomechanical, and elemental studies were performed. Methods Forty 12-week-old Sprague-Dawley rats received an ovariectomy (OVX) or were sham-operated (sham). Twenty-one weeks later, tibias of subgroups of sham-operated and OVX animals were subjected to serial local iontophoresis (IOP) treatments, received systemic subcutaneous 17β-estradiol (E2), or were treated with the combination of IOP and E2. Changes in bone density were detected by quantitative ultrasound densitometry and expressed as amplitude-dependent speed of sound (AD-SoS). Biomechanical studies and elemental analysis were performed at the end of the experiments. Results Osteopenia developed 21 weeks after OVX in the proximal tibial regions; the mean difference estimate (95% confidence intervals) of AD-SoS values between the sham-operated and OVX animals was 188.7 (140.4–237.1). Serial iontophoretic treatment resulted in an increase in bone density in both sham-operated and OVX animals (sham+IOP versus sham: 121.4 [73.01–169.7]; OVX+IOP versus OVX: 241.6 [193.2–289.9]). Similar changes in AD-SoS were detected after 17β-estradiol (E2) treatment; however, even greater changes occurred after OVX+E2+IOP versus OVX+E2 (123.4 [75.1–171.8]). Similar improvements also were evident regarding the biomechanical features of the tibias. Limitations A limitation of this study was the relatively small number of rats. Conclusions The efficacy of local IOP using calcium- and phosphate-donating microparticles is comparable to that of estrogen therapy as evidenced by steadily increasing bone density, restoration of the calcium and phosphate balance, and improvement in the biomechanical properties of the bone.

scholarly journals Inflammation: a putative link between phosphate metabolism and cardiovascular disease

2021 ◽  
Vol 135 (1) ◽  
pp. 201-227
Author(s):  
Jakob Voelkl ◽  
Daniela Egli-Spichtig ◽  
Ioana Alesutan ◽  
Carsten A. Wagner
Keyword(s):  
Cardiovascular Disease ◽  
Vascular Calcification ◽  
Hormonal Regulation ◽  
Dietary Habits ◽  
Inflammatory Responses ◽  
Fibroblast Growth Factor 23 ◽  
Serum Phosphate ◽  
Phosphate Homeostasis ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk

Abstract Dietary habits in the western world lead to increasing phosphate intake. Under physiological conditions, extraosseous precipitation of phosphate with calcium is prevented by a mineral buffering system composed of calcification inhibitors and tight control of serum phosphate levels. The coordinated hormonal regulation of serum phosphate involves fibroblast growth factor 23 (FGF23), αKlotho, parathyroid hormone (PTH) and calcitriol. A severe derangement of phosphate homeostasis is observed in patients with chronic kidney disease (CKD), a patient collective with extremely high risk of cardiovascular morbidity and mortality. Higher phosphate levels in serum have been associated with increased risk for cardiovascular disease (CVD) in CKD patients, but also in the general population. The causal connections between phosphate and CVD are currently incompletely understood. An assumed link between phosphate and cardiovascular risk is the development of medial vascular calcification, a process actively promoted and regulated by a complex mechanistic interplay involving activation of pro-inflammatory signalling. Emerging evidence indicates a link between disturbances in phosphate homeostasis and inflammation. The present review focuses on critical interactions of phosphate homeostasis, inflammation, vascular calcification and CVD. Especially, pro-inflammatory responses mediating hyperphosphatemia-related development of vascular calcification as well as FGF23 as a critical factor in the interplay between inflammation and cardiovascular alterations, beyond its phosphaturic effects, are addressed.

scholarly journals Research Models for Studying Vascular Calcification

2020 ◽  
Vol 21 (6) ◽  
pp. 2204 ◽  
Author(s):  
Jaqueline Herrmann ◽  
Milen Babic ◽  
Markus Tölle ◽  
Markus van der Giet ◽  
Mirjam Schuchardt
Keyword(s):  
Animal Models ◽  
Vascular Calcification ◽  
Ex Vivo ◽  
Systemic Disease ◽  
Treatment Options ◽  
Aortic Tissue ◽  
Cardiovascular Morbidity And Mortality ◽  
Culture Models

Calcification of the vessel wall contributes to high cardiovascular morbidity and mortality. Vascular calcification (VC) is a systemic disease with multifaceted contributing and inhibiting factors in an actively regulated process. The exact underlying mechanisms are not fully elucidated and reliable treatment options are lacking. Due to the complex pathophysiology, various research models exist evaluating different aspects of VC. This review aims to give an overview of the cell and animal models used so far to study the molecular processes of VC. Here, in vitro cell culture models of different origins, ex vivo settings using aortic tissue and various in vivo disease-induced animal models are summarized. They reflect different aspects and depict the (patho)physiologic mechanisms within the VC process.

scholarly journals Inflammation of adipose tissue. Is there a place for statins to correct adiposopathy?

2019 ◽  
Vol 16 (1) ◽  
pp. 12-19
Author(s):  
Daria A. Borodkina ◽  
Olga V. Gruzdeva ◽  
Elena V. Palicheva ◽  
Olga L. Barbarash
Keyword(s):  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Cholesterol Biosynthesis ◽  
Living Organism ◽  
Endocrine Function ◽  
Clinical Effects ◽  
Key Factor ◽  
Coa Reductase

This review is devoted to the analysis of data on the effect of inhibitors of 3-hydroxy-3-methylglutaryl coenzymate-reductase on the endocrine function of adipose tissue in obesity. Violation of metabolism of adipose tissue, as well as the amount of fat, are a a key factor in the pathophysiology of obesity and the development of concomitant diseases. Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl-kofermenta reductase (HMG-COA reductase) that catalyze the initial stage of cholesterol biosynthesis in the liver. Therefore, traditionally, the liver is considered as the main target organ for statins. The results of studies of molecular mechanisms of action of statins on carbohydrate and lipid metabolism, adipokine and inflammatory balance in adipose tissue on the example of isolated adipocytes (in vivo) and in living organism (in vitro) are presented. Effect of statins on the action of insulin, as well as the possibility of developing pathological conditions associated with insulin resistance and the development of type 2 diabetes mellitus (DM 2). The proven clinical effects of cholesterol-lowering action of statins, allow new insights and to further explore their possible impact on other links in the development of obesity, and potentially to use them as therapeutic agents for pharmacological correction of obesity and the fight against cardiovascular diseases.

Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

1982 ◽  
Vol 40 ◽  
pp. 210-211
Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman
Keyword(s):  
Cultured Cells ◽  
Human Tumor ◽  
Cell Type ◽  
Tumor Mass ◽  
Initial Cell ◽  
Cloning Assay ◽  
Human Tumor Cloning ◽  
The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

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