osteoprotegerin and Arteriosclerosis

Several clinical studies has been shown the close relationship between osteoporosis and arteriosclerosis, and basic researches confirmed the reasonability of this association by the findings that organized molecular mechanism of bone formation in bone tissue was also observed in the lesion of vascular calcification, RANK/RANKL/OPG axis is one of potent and explainable molecular mechanism for bone-vascular association. However, one recent clinical intervetion study using RANKL antibody for post menopauisal women with primary osteoporosis could not validate that relationship. Further examinations are needed to improve understanding of the precise mechanism in this area.

Topics: Animals; Arteriosclerosis; Bone and Bones; Humans; Osteogenesis; Osteoporosis; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Vascular Calcification

Initially described as key regulators in metabolic bone disease osteoprotegerin (OPG), receptor activator of nuclear factor kappa B (RANK) and RANK ligand (RANKL) have also been discriminated as regulators in immunologic function. Cardiovascular diseases (CVD) develop over many years in life and are often triggered by inflammatory processes within the vessel wall that lead to vascular remodeling. Recently some study groups have described OPG as a prognostic parameter for mortality and morbidity in cardiovascular patients.

Topics: Adult; Age Factors; Aged; Arteriosclerosis; Bone Density; Bone Resorption; Cardiovascular Diseases; Coronary Disease; Female; Gonadal Steroid Hormones; Heart Failure; Humans; Male; Middle Aged; Osteoclasts; Osteoporosis; Osteoprotegerin; Prognosis; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Sex Factors; Ventricular Dysfunction, Left; Young Adult

Osteoprotegerin (OPG) is a bone-related protein that is also present in the vasculature. Recent data suggest that it may play a special role in arterial disease among patients with diabetes. Diabetic macroangiopathy is characterized by a series of diffuse, non-atherosclerotic alterations that hypothetically increase the vulnerability of the vessel wall to atherogenic processes. One prominent feature of the macroangiopathy is linear media calcifications, which have been found to impose a strong risk of future cardiovascular events in epidemiological studies. The mechanisms behind the development of calcifications are unknown, but may be related to the occurrence of diffuse matrix alterations in the arterial wall in diabetes. Interestingly, we have recently observed that the amounts of OPG are increased in the tunica media in arterial tissue from diabetic patients. OPG has been linked to vascular calcifications in immunohistochemical analysis of atherosclerotic tissue and experimental studies on OPG knockout mice. Thus, it is possible that increased arterial OPG concentrations reflect an osteogenic transformation of the vasculature in patients with diabetes as an aspect of diabetic macroangiopathy. This review will evaluate data about OPG in the vasculature and focus on a possible role of OPG in the arterial wall in diabetes.

Topics: Animals; Arteriosclerosis; Calcinosis; Diabetic Angiopathies; Endothelium, Vascular; Glycoproteins; Humans; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor

Vascular calcification, long thought to result from passive degeneration, involves a complex, regulated process of biomineralization resembling osteogenesis. Evidence indicates that proteins controlling bone mineralization are also involved in the regulation of vascular calcification. Artery wall cells grown in culture are induced to become osteogenic by inflammatory and atherogenic stimuli. Furthermore, osteoclast-like cells are found in calcified atherosclerotic plaques, and active resorption of ectopic vascular calcification has been demonstrated. In general, soft tissue calcification arises in areas of chronic inflammation, possibly functioning as a barrier limiting the spread of the inflammatory stimulus. Atherosclerotic calcification may be one example of this process, in which oxidized lipids are the inflammatory stimulus. Calcification is widely used as a clinical indicator of atherosclerosis. It progresses nonlinearly with time, following a sigmoid-shaped curve. The relationship between calcification and clinical events likely relates to mechanical instability introduced by calcified plaque at its interface with softer, noncalcified plaque. In general, as calcification proceeds, interface surface area increases initially, but eventually decreases as plaques coalesce. This phenomenon may account for reports of less calcification in unstable plaque. Vascular calcification is exacerbated in certain clinical entities, including diabetes, menopause, and osteoporosis. Mechanisms linking them must be considered in clinical decisions. For example, treatments for osteoporosis may have unanticipated effects on vascular calcification; the converse also applies. Further understanding of processes governing vascular calcification may yield new therapeutic options for vascular disease.

Topics: Animals; Arteriosclerosis; Calcinosis; Calcium-Binding Proteins; Diabetes Mellitus; Endpoint Determination; Extracellular Matrix Proteins; Glycoproteins; Humans; Matrix Gla Protein; Menopause; Mice; Mice, Knockout; Minerals; Osteogenesis; Osteopontin; Osteoporosis; Osteoprotegerin; Phosphates; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Sialoglycoproteins

Vascular calcification often occurs with advancing age, atherosclerosis, various metabolic disorders such as diabetes mellitus and end-stage renal disease, or in rare genetic diseases, leading to serious clinical consequences. Such mineralization can occur at various sites (cardiac valves, arterial intima or media, capillaries), involve localized or diffuse widespread calcification, and result from numerous causes that provoke active inflammatory and osteogenic processes or disordered mineral homeostasis. Although valuable research has defined many key factors and cell types involved, surprising new insights continue to arise that deepen our understanding and suggest novel research directions or strategies for clinical intervention in calcific vasculopathies. One emerging area in vascular biology involves the RANKL/RANK/OPG system, molecules of the tumor necrosis factor-related family recently discovered to be critical regulators of immune and skeletal biology. Evidence is accumulating that such signals may be expressed, regulated, and function in vascular physiology and pathology in unique ways to promote endothelial cell survival, angiogenesis, monocyte or endothelial cell recruitment, and smooth muscle cell osteogenesis and calcification. Concerted research efforts are greatly needed to understand these potential roles, clarify whether RANKL (receptor activator of nuclear factor kappaB ligand) promotes and osteoprotegerin (OPG) protects against vascular calcification, define how OPG genetic polymorphisms relate to cardiovascular disease, and learn whether elevated serum OPG levels reflect endothelial dysfunction in patients. Overall, the RANKL/RANK/OPG system may mediate important and complex links between the vascular, skeletal, and immune systems. Thus, these molecules may play a central role in regulating the development of vascular calcification coincident with declines in skeletal mineralization with age, osteoporosis, or disease.

Topics: Animals; Arteriosclerosis; Bone and Bones; Calcinosis; Carrier Proteins; Endothelium, Vascular; Glycoproteins; Humans; Immune System; Membrane Glycoproteins; Mice; Mice, Knockout; Muscle, Smooth, Vascular; Osteoclasts; Osteoporosis; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Vascular Diseases

Patients with end-stage renal disease have greatly elevated risks of atherosclerotic disease. Vascular calcification in advanced atherosclerosis is a common feature in ESRD patients. Risk factors of atherosclerosis in ESRD patients are coronary risk factors such as hypertension, diabetes and hyperlipidemia and hyperphosphatemia. Bone associated proteins including osteopontin, matrix Gla protein and osteoprotegerin may be involved in the progression of atherosclerosis.

Topics: Arteriosclerosis; Calcium-Binding Proteins; Diabetes Complications; Diabetes Mellitus; Extracellular Matrix Proteins; Glycoproteins; Humans; Hyperlipidemias; Hypertension; Kidney Failure, Chronic; Matrix Gla Protein; Osteopontin; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Risk Factors; Sialoglycoproteins

Topics: Animals; Arteries; Arteriosclerosis; Calcinosis; Calcium-Binding Proteins; Extracellular Matrix; Extracellular Matrix Proteins; Glycoproteins; Humans; Matrix Gla Protein; Minerals; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Vascular Diseases

BACKGROUND Receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), cartilage oligomeric matrix protein (COMP), bone morphogenetic protein (BMP-2), and fibroblast growth factor 23 (FGF-23) are involved in inflammation, calcium deposition, and fibrosis of blood vessels. Acute changes in these factors may contribute to the progression of arteriosclerosis, especially if their elevated serum levels persist postoperatively. MATERIAL AND METHODS A total of 90 patients (79 White, 4 African American, and 7 Other) undergoing elective heart surgery were enrolled in the study. Blood was collected before surgery and after surgery at 24 hours, 7 days, and 3 months to allow for longitudinal comparisons. After the plasma isolation, several biomarkers levels were studied using an enzymatic-linked assay. Demographic and clinical information were obtained from electronic health records. RESULTS At 24 hours after surgery, RANKL (RANKLbaseline=248.7±215.7 vs RANKLt24h=376.4±329.7; P=0.035), and BMP-2 (BMP-2baseline=283.7±255.4 vs BMP-2t24h=482.4; P=0.015) were significantly elevated compared to baseline, with levels returning to baseline at 7 days. FGF-23 increased significantly from baseline (FGF-23baseline=1020±1210) to 7 days (FGF-237d=2191±5188; P=0.029) and remained significantly higher than baseline at 3 months (FGF-233m=2041±3521; P=0.044). White blood cells (WBC) remained elevated at discharge (WBCbaseline=6.8±2.1 vs WBC24h=15.0±5.3 vs WBCdischarge=8.8±3.4). IL-8 and C-reactive protein normalized at 3 months. Estimated blood loss was significantly correlated with RANKL at 24 hours (r²=0.33; P=0.035). Serum creatinine levels after surgery at 24 hours (r²=0.41; p=0.008) and 7 days (r²=0.59; P=0.000) was strongly correlated with COMP. CONCLUSIONS Persistent elevation of serum FGF-23 indicates a potential for accelerated arteriosclerosis after cardiac surgery.

Topics: Arteriosclerosis; Cardiac Surgical Procedures; Cartilage Oligomeric Matrix Protein; Convalescence; Fibroblast Growth Factor-23; Humans; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B

Topics: Arteriosclerosis; Cross-Sectional Studies; Female; Humans; Mastocytosis, Systemic; Osteoprotegerin

Abdominal Aortic Aneurysm (AAA) is multifactorial disease with unknown ethiology. Among the theories on the pathogenesis of AAA are some ge. netic factors, infections, disorders in connective tissue (collagenosis), arteriosclerosis, inflammation, incorrect immune response (autoimmunity). It was discovered that crucial for AAA development is intense inflammatory reaction combined with high proteolytic activity. Recent evidence confirmed the association between osteopontin (OPN) and osteoprotegerin (OPG) levels and cardiovascular diseases and arterio. sclerosis. The aim of this work was assessment of plasma levels of OPN and OPG in the group of the patients with AAA and correlation of results with clinical parameters, "classical" risk factors for development of AAA, arteriosclerosis and morbidity. The reference group consist of the patients with Leriche Syndrome (LS). The OPG level was assessed in plasma and OPN levels were assessed in plasma and urine. Plasma OPG levels were higher in AAA group than in LS group (difference not statistically significant, p = 0.0549). It was statistically significant positive correlation between plasma OPN levels and CRP levels in the groups of AAA and LS patients. It was not any association between plasma OPG and OPN levels and abdominal aortic diameter. Plasma OPG levels correlated positively with the existence of coronary artery disease in AAA patients. Insignificant, but higher levels of this protein were found also in a group of AAA patient with myocardial infarction. In LS group we found statistically significant positive association between plasma OPG levels and patient with stroke. However, in AAA patients with incidence of stroke, we found higher plasma levels of OPN. Interestingly, there was not any association between OPN levels in the urine and clinical parameters, risk factors and morbidity, including kidney diseases. inflammatory role of OPN and depicts better reflection of inflammatory reaction of OPN than OPG in both group of patients. Plasma OPG levels in AAA patients are more associated with coronary artery disease than with peripheral artery disease, what is characteristic for LS patients. Lack of association of urine OPN levels with above mentioned parameters suggest minor importance of this urine protein in clinical condition evaluation of patients with AAA and advanced arteriosclerosis.

Topics: Aged; Aortic Aneurysm, Abdominal; Arteriosclerosis; Biomarkers; Comorbidity; Coronary Artery Disease; Female; Humans; Kidney Diseases; Male; Middle Aged; Osteopontin; Osteoprotegerin; Risk Factors; Stroke

Patients on hemodialysis exhibit a drastically increased cardiovascular mortality. Inflammation, hyperphosphatemia and lack of calcification inhibitors are uremia-associated risk factors for vascular calcification. Functional and morphological vascular parameters are used to assess cardiovascular risk. The aim of our study was to analyse the relation between pulse wave velocity (PWV) and intima-media-thickness (IMT) with calcification inhibitors.. A cohort of 97 hemodialysis patients was consecutively selected and investigated (age 56 +/- 9 years). Carotid-femoral PWV, carotid IMT, left ventricular ejection fraction and septum thickness were determined. These parameters were correlated with serum levels of CRP and calcification inhibitors (fetuin-A and osteoprotegerin [OPG]).. Both PWV and IMT showed a positive correlation with age and systolic blood pressure and a negative correlation with Kt/V (dialysis efficiency). Additionally, fetuin-A was negatively associated with CRP and positively with cholesterol and triglycerides. Serum levels of the calcification inhibitors fetuin-A and OPG were not correlated to PWV or IMT.. The lack of correlation of calcification inhibitors with PWV and IMT means that functional and morphological measurements of vascular properties can not necessarily be replaced by analysing "biomarkers".

Topics: Aging; alpha-2-HS-Glycoprotein; Arteriosclerosis; Blood Pressure; Blood Proteins; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Female; Humans; Male; Middle Aged; Osteoprotegerin; Pulse; Renal Dialysis; Triglycerides; Tunica Intima; Tunica Media

Patients with vascular calcifications often have low bone mineral density (BMD), but it is still uncertain if osteoporosis and peripheral vascular disease (VD) are interrelated and linked by a common pathomechanism. Moreover, data on bone turnover in patients with advanced atherosclerosis are lacking. We measured BMD by dual-energy X-ray absorptiometry (DXA) and quantitative bone ultrasound (QUS), as well as the serum levels of osteocalcin (OC), bone-specific alkaline phosphatase (BAP), osteoprotegerin (OPG) and its ligand RANKL, and the urinary concentration of the C-terminal telopeptides of type I collagen (CrossLaps), in 36 patient (20 male and 16 female) with serious atherosclerotic involvement of the carotid and/or femoral artery to investigate the underlying mechanism of vascular and osseous disorders. Thirty age-matched and gender matched healthy individuals served as controls. After adjustment for age, BMD was significantly reduced at the lumbar spine in 23/36 (63%) patients (mean T score -1.71+/-1.42) and at the proximal femur in 34/36 (93%) patients (neck mean T score -2.5+/-0.88). Ten patients (27%) had abnormal QUS parameters. Gender and diabetes had no effect on the relationship between vascular calcification and bone density at any site measured. VD subjects had OC and BAP serum levels lower than controls (13.3+/-3.1 vs 27.7+/-3.3 ng/ml, P<0.01, and 8.4+/-2.3 vs 12.5+/-1.4 microg/l, P<0.01, respectively). Urinary CrossLaps excretion was not significantly different in patients with VD and in controls (257.9+/-138.9 vs 272.2+/-79.4 micro g/mmol Cr, respectively). Serum OPG and RANKL levels were similar in patients and in controls (3.5+/-1.07 vs 3.4+/-1.05 pmol/l, and 0.37+/-0.07 vs 0.36+/-0.06 pmol/l, respectively). We proved high occurrence of osteoporosis in VD, with evidence of age and gender independence. Negative bone remodelling balance would be a consequence of reduced bone formation, with no apparent increased activation of the OPG-RANKL system.

Topics: Absorptiometry, Photon; Aged; Arteriosclerosis; Biomarkers; Bone Density; Bone Remodeling; Calcinosis; Carotid Artery Diseases; Collagen; Female; Femoral Artery; Glycoproteins; Humans; Male; Middle Aged; Osteocalcin; Osteoporosis; Osteoprotegerin; Peptide Fragments; Peripheral Vascular Diseases; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Ultrasonography

The aim of this study was to compare the concentration of osteoprotegerin (OPG), receptor activator of nuclear factor kappaB ligand (RANKL), and osteopontin (OPN) in stable (asymptomatic) and unstable (symptomatic) carotid atherosclerosis. In addition, we were interested in the effect of angiotensin II blockade on the secretion of these proteins by unstable atherosclerosis.. Endarterectomy samples removed from patients with recent (within 6 weeks) or no previous focal neurological symptoms were assessed by immunohistochemistry, Western analysis, and explant culture. Concentrations of OPG, RANKL, and OPN were measured by mean optical density (MOD), densitometry of protein bands, and enzyme-linked immunosorbent assay of supernatants from explant culture, and compared between symptomatic and asymptomatic patients.. The concentration of OPG and OPN within the proximal internal carotid (PIC) part of the endarterectomy specimen removed from symptomatic patients was elevated 2- and 4-fold, respectively. Although the concentration of RANKL did not differ according to patients' symptoms, the quantity of OPG secreted by explants of the PIC was greater in explants from symptomatic patients and could be significantly reduced within 48 hours of incubation with the angiotensin II blocker irbesartan.. OPG and OPN are upregulated in symptomatic human carotid atherosclerosis with possible implications for plaque stability. Angiotensin II blockade is able to downregulate OPG secretion in vitro.

Topics: Aged; Angiotensin II; Arteriosclerosis; Biphenyl Compounds; Blotting, Western; Carotid Stenosis; Carrier Proteins; Culture Techniques; Female; Glycoproteins; Humans; Immunohistochemistry; Irbesartan; Male; Membrane Glycoproteins; Middle Aged; Osteopontin; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Sialoglycoproteins; Tetrazoles; Up-Regulation

Vascular calcification may occur at different areas of the vessel wall, including the intima in atherosclerosis and the media in Mönckeberg's sclerosis. Medial calcification of arteries is common in patients with diabetes mellitus or chronic renal failure. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand are essential modulators of bone homeostasis and may be involved in the process of vascular calcification. In this study we investigated arteries from patients with Mönckeberg's sclerosis and atherosclerosis. Apoptosis, which precedes vascular calcification in vitro, was assessed by an in situ ligation assay and was localized to the medial layer of arteries (Mönckeberg's sclerosis) and the neointima (atherosclerosis). Immunohistochemistry and in situ hybridization revealed OPG immunoreactivity and mRNA expression surrounding calcified areas in the medial layer (Mönckeberg's sclerosis), whereas OPG was mainly expressed adjacent to calcified neointimal lesions (atherosclerosis). Receptor activator of nuclear factor-kappaB ligand protein and mRNA were barely or not detectable. Of note, TNF-related apoptosis-inducing ligand, an inducer of apoptosis that is also blocked by OPG, displayed a similar spatial distribution as OPG. In summary, we demonstrate enhanced apoptosis adjacent to vascular calcification, and the concurrent expression of regulators of apoptosis and osteoclastic differentiation, TNF-related apoptosis-inducing ligand and OPG, suggesting their involvement in the pathogenesis of vascular calcification.

Topics: Aged; Aged, 80 and over; Apoptosis Regulatory Proteins; Arteriosclerosis; Calcinosis; Carrier Proteins; Case-Control Studies; Female; Glycoproteins; Humans; Immunohistochemistry; In Situ Hybridization; Male; Membrane Glycoproteins; Middle Aged; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; RNA, Messenger; Staining and Labeling; Tissue Distribution; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha; Vascular Diseases

The aortic calcification index (ACI), estimated on abdominal computed tomographic scans, has been associated with the extent of arteriosclerosis in hemodialysis patients. However, the contribution of biochemical markers to the progression of vascular calcification in patients undergoing hemodialysis is not fully understood.. We examined the relationship between coronary risk factors; metabolic factors, including serum osteoprotegerin (OPG) concentration; and progression of vascular calcification in 26 dialysis patients.. Mean patient age was 52.6 +/- 8.7 (SD) years, and mean duration of dialysis therapy was 7.7 +/- 5.8 years. ACI was measured twice in each patient, and the mean interscan period was 4.9 +/- 0.3 years. Mean ACI changed from 22.2 +/- 24.2 to 33.9 +/- 28.8 overall, and mean change in ACI (DeltaACI) was 12.0 +/- 9.9. Patients were divided into 2 groups: slow progressors, with DeltaACI of 4.1 +/- 3.2 (n = 13), and rapid progressors, with DeltaACI of 19.8 +/- 7.9 (n = 13). Serum fasting glucose and CRP levels of rapid progressors were high, and their serum albumin and intact parathyroid hormone levels were low. Multiple regression analyses showed that serum OPG levels were independently associated with vascular calcification in the hemodialysis patients studied.. Rapid progression of vascular calcification was associated with dose of calcium carbonate prescribed and serum OPG concentration. The clinical significance of these observations remains to be determined.

Topics: Aortic Diseases; Arteriosclerosis; C-Reactive Protein; Calcinosis; Calcium; Calcium Carbonate; Disease Progression; Female; Glycoproteins; Humans; Kidney Failure, Chronic; Lipids; Longitudinal Studies; Male; Middle Aged; Osteoprotegerin; Parathyroid Hormone; Phosphorus; Prospective Studies; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Renal Dialysis; Risk Factors

Increasing evidence indicates an important role of PPAR gamma activation in modulating the development and progression of atherosclerosis, however, the mechanisms involved in these effects are not well understood since the PPAR gamma-regulated genes in vascular smooth muscle cells (VSMC) are poorly defined. Here we reported that PPAR gamma ligands, GW7845, ciglitazone and troglitazone had the effect of inhibiting osteoprotegerin (OPG) expression in human aortic smooth muscle cells (HASMC). The effect of GW7845 and ciglitazone on OPG expression was completely abolished by GW9662, a PPAR gamma antagonist. Overexpression of PPAR gamma in HASMC by the infection of a PPAR gamma adenovirus dramatically decreased OPG expression. In addition, PPAR gamma activation inhibited OPG promoter activity. Taken together, our data suggest that OPG expression is a novel PPAR gamma target gene in VSMC and downregulation of OPG expression by PPAR gamma activation provides a new insight into the understanding of the role of PPAR gamma in atheroscelrosis and hypertension.

Topics: Arteriosclerosis; Cells, Cultured; Gene Expression Regulation; Glycoproteins; Humans; Muscle, Smooth, Vascular; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Signal Transduction; Transcription Factors

In the present study, we examined the expression of regulators of bone formation and osteoclastogenesis in human atherosclerosis because accumulating evidence suggests that atherosclerotic calcification shares features with bone calcification. The most striking finding of this study was the constitutive immunoreactivity of matrix Gla protein, osteocalcin, and bone sialoprotein in nondiseased aortas and the absence of bone morphogenetic protein (BMP)-2, BMP-4, osteopontin, and osteonectin in nondiseased aortas and early atherosclerotic lesions. When atherosclerotic plaques demonstrated calcification or bone formation, BMP-2, BMP-4, osteopontin, and osteonectin were upregulated. Interestingly, this upregulation was associated with a sustained immunoreactivity of matrix Gla protein, osteocalcin, and bone sialoprotein. The 2 modulators of osteoclastogenesis (osteoprotegerin [OPG] and its ligand, OPGL) were present in the nondiseased vessel wall and in early atherosclerotic lesions. In advanced calcified lesions, OPG was present in bone structures, whereas OPGL was only present in the extracellular matrix surrounding calcium deposits. The observed expression patterns suggest a tight regulation of the expression of bone matrix regulatory proteins during human atherogenesis. The expression pattern of both OPG and OPGL during atherogenesis might suggest a regulatory role of these proteins not only in osteoclastogenesis but also in atherosclerotic calcification.

Topics: Adult; Aged; Aorta, Abdominal; Arteriosclerosis; Calcinosis; Calcium-Binding Proteins; Carrier Proteins; Disease Progression; Extracellular Matrix Proteins; Female; Glycoproteins; Humans; Immunohistochemistry; In Situ Hybridization; Male; Matrix Gla Protein; Membrane Glycoproteins; Middle Aged; Osteoblasts; Osteoclasts; Osteogenesis; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; RNA, Messenger; Seminal Vesicle Secretory Proteins; Tunica Intima; Xanthomatosis

Calcification of extracellular matrix (ECM) can be either physiological or pathological. Physiological calcification (or mineralization) of ECM is restricted to bones, teeth and, to a lesser extent, growth plate cartilages. Pathological calcification appears often in the ECM of arteries where it is a frequent complication of atherosclerosis. However, calcification of the ECM of arteries is not restricted to atherosclerosis. Indeed, human diseases have been described that are characterized by calcification of the aortic media in the absence of any atherosclerotic lesions. The existence of these rare diseases, along with several mouse models recently generated and discussed below, indicates that the formation of atherosclerotic lesions and the calcification of the artery ECM are controlled by different genetic pathways. This emerging knowledge has implications for our understanding of ECM calcification beyond atherosclerosis.

Topics: Animals; Arteries; Arteriosclerosis; Calcinosis; Calcium-Binding Proteins; Extracellular Matrix; Extracellular Matrix Proteins; Glycoproteins; Humans; Matrix Gla Protein; Mice; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Vascular Diseases; Vitamin K