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Siegfried Hagl

Publications and source records attributed to Siegfried Hagl.

At least 37 records · Page 2Linked to original sources
PubMed2005

Increased aortic wall stress in aortic insufficiency: clinical data and computer model.

OBJECTIVE: The study was aimed at determining which cardiac pathologies are associated with increased longitudinal stress in the aorta and therefore may be responsible for the intimal transverse tears seen in aortic dissections. METHODS: Aortic root contrast injections were analyzed in 90 cardiac patients to measure the downward motion of the annulus during a cardiac cycle. A finite element model of the pressurized aortic root, arch and supra-aortic vessels was created to assess the influence of the aortic root motion on the aortic wall stress. RESULTS: The axial displacement of the aortic root ranged from 0 to 14 mm. A multivariate analysis showed that aortic insufficiency (AI) grade, hypokinesis of the left ventricle (HKI), and myocardial hypertrophy (HTR) were 3 independent variables which correlated with the axial displacement of the aortic root (DISP), such that ARM (mm)=5.379 (P<0.0001) +1.186 x AI grade (P=0.0016) - 1.611 x HKI (P=0.0078) - 1.399 x HTR (P=0.0355) with R2=0.23. The major finding of the stress analysis was that in the ascending aorta, at approximately 2 cm above the sino-tubular junction, the longitudinal stress due to aortic root motion was 32% higher in patients with AI than in patients without AI, thereby increasing the risk of transverse intimal rupture. CONCLUSIONS: Cardiac patients with AI are likely to experience enhanced longitudinal stress in the ascending aorta due to increased aortic root motion. Thus, these patients should be targeted and their aortic root movement monitored because it may be an important risk factor for aortic dissection.

Adult↗
PubMed2005

Intraoperative assessment of right ventricular volume and function.

OBJECTIVE: Right ventricular function is an important aspect of global cardiac performance which affects patients' outcome after cardiac surgery. Due to its geometrical complexity, the assessment of right ventricular function is still a very difficult task. Aim of this study was to investigate the value of a new technique for intraoperative assessment of right ventricle based on transesophageal 3D-echocardiography, and to compare it to volumetric thermodilution by using a new generation of fast response thermistor pulmonary artery catheters. METHODS: Twenty-five patients with coronary artery disease underwent 68 intraoperative measurements by 3D-echocardiography and thermodilution simultaneously. Following parameters were analysed: right ventricular end-diastolic volume (RVEDV), end-systolic volume (RVESV) and ejection fraction (RVEF). Pulmonary, systemic and central venous pressures were simultaneously recorded. Segmentation of right ventricular volumes were obtained by the 'Coons-Patches' technique, which was implemented into the EchoAnalyzer, a multitask system developed at our institution for three-dimensional functional and structural measurements. RESULTS: Right ventricular volumes obtained by 3D-echocardiography did not show significant correlations to those obtained by thermodilution. Volumetric thermodilution systematically overestimates right ventricular volumes. Significant correlations were found between RVEF measured by 3D-echocardiography and those obtained by thermodilution (r=0. 93; y=0.2+0.80x; SEE=0.03; P<0.01). Bland-Altmann analysis showed that thermodilution systematically underestimates RVEF. The bias for measuring RVEF was +15.6% with a precision of +/-4.3%. The patients were divided into two groups according to left ventricular function. The group of patients with impaired function showed significantly lower right ventricular ejection fraction (44.1+/-4.6 vs. 55.1+/-3.9%; P<0.01). CONCLUSIONS: Three-dimensional echocardiography provides a useful non-invasive tool for intraoperative and serial assessment of right ventricular function. This new technique, which overcomes the limitations of previous methods, may offer key insights into management and outcome of patients with severe impairment of cardiac function.

Aged↗
PubMed2005

Effectivity of a T-cell-adapted induction therapy with anti-thymocyte globulin (Sangstat).

BACKGROUND: Cytolytic induction therapy with anti-thymocyte globulin (ATG) should induce effective immunosuppression, with a low rate of rejection in the initial phase after heart transplantation. Induction therapy with ATG allows post-operative renal recovery without the negative effects of highly nephrotoxic cyclosporine levels. An increased rate of infection is a common problem, however, and has been associated with "over-immunosuppression" early after transplantation. Therefore, we investigated whether reduced T-cell-adapted ATG induction therapy could be performed without increasing the risk of graft loss by rejection and whether reductions in infection rates and costs are possible. METHODS: Between March 1999 and December 2002, T-cell-adapted ATG induction therapy with ATG (Sangstat) (1.5 mg/kg) was given to 62 heart transplant recipients (study group) starting on post-operative Days 1 to 6. T-lymphocyte sub-populations were screened daily using flow cytometry. If total lymphocytes were <100/microl (reference 1,300 to 2,300/microl), T-helper lymphocytes (CD4+) <50/microl (reference >500/microl) and T-suppressor cells (CD8+) <50/microl (reference >300/microl), then no ATG was given. Further immunosuppression was continued with triple therapy consisting of methylprednisolone, azathioprine and cyclosporine. An historic group of heart transplant recipients given a full-dose ATG regimen for 8 days served as controls. These recipients were treated with ATG (Merieux 1.5 mg/kg) until reaching monoclonal cyclosporine levels of >300 mg/dl. Additional immunosuppressive treatment did not differ. Patients in both groups received systemic antibiotics (Imipenem) peri-operatively. Results of routine endomyocardial biopsies and rates of infections were examined. RESULTS: Study group patients were older (52 +/- 10 vs 49 +/- 14 years). In the study group, mean cumulative ATG dose was reduced significantly to 596 +/- 220 mg (p < 0.05) for 3.9 +/- 1.6 days compared with 1,159 +/- 376 mg for 6.9 +/- 1.1 days in the control group. The rate of cytomegalovirus (CMV) seroconversion was 23% in the study group compared with 13% in the control group. Rate of deep sternal infections was lower in the study group (1.6% vs 3.2%). The mean rejection rate in the first 3 months was 0.4 +/- 0.7 for the study patients (185 biopsies) vs 1.1 +/- 1.7 for controls (237 biopsies). All biopsies with ISHLT Grade >2 were treated successfully with 1,000 mg of methylprednisolone intravenously for 3 days. Both groups showed a similar 1-year survival rate (study 88%, control 89%). CONCLUSIONS: T-cell-adapted ATG induction therapy can be a helpful tool for individualized immunosuppression. It is not associated with an increased rate of rejection. Lower doses of immunosuppression help to minimize the rates of infection. In addition, cytolytic induction therapy combined with reduced ATG results in significant cost reduction.

Adult↗
PubMed2005

Simultaneous management of congenital tracheal stenosis and cardiac anomalies in infants.

OBJECTIVE: The present article aims to describe our experience with patients who underwent simultaneous repair of congenital tracheal stenosis and cardiac anomalies. METHODS: Between January 2000 and December 2003, 9 infants underwent simultaneous surgical repair of a congenital tracheal stenosis and congenital heart disease. The intraoperative findings revealed localized tracheal stenosis in 3 patients. The funnel-type tracheal stenosis was present in 6 patients. Associated cardiac anomalies included ostium secundum atrial septal defect in 5 patients and ventricular septal defect in 2 patients, pulmonary artery sling in 4 patients, patent ductus arteriosus in 6 patients, atrioventricular septal defect in 1 patient, aortic arch hypoplasia in 1 patient, coarctation of the aorta in 1 patient, and partial anomalous pulmonary venous connection in 2 patients, one of them with "scimitar syndrome." Tracheal origin of the right upper lobe was diagnosed in 2 of the patients. A right aberrant subclavian artery (lusoria) was found in one patient. All patients were operated on through a median sternotomy and with cardiopulmonary bypass. Tracheal resection with direct end-to-end anastomosis was performed in all cases. RESULTS: There was no operative mortality. One patient died 6 weeks postoperatively. Eight patients were extubated between the 14th and 30th postoperative days under bronchoscopic monitoring. The extubation was performed after a stepwise respirator-weaning program. Postoperative endoscopic examination showed adequate airway dimensions and patency in every case. The midterm results after a mean follow-up of 37 months (range, 16-58 months) of the entire group demonstrate a stabile and complication-free clinical outcome. CONCLUSIONS: We advocate our current strategy for infants with congenital tracheal stenosis: resection with end-to-end anastomosis and simultaneous repair of associated intracardiac anomalies.

Female↗
PubMed2005

Influence of receptor activator of nuclear factor kappa B on human aortic valve myofibroblasts.

Calcific aortic valve stenosis, the main heart valve disease in the elderly, is based on progressive calcification and fibrous thickening of the valve. Several reports addressed the pathogenesis of tissue calcification in this disorder, but few data exist on the molecular mechanisms of the fibrosis and remodeling of the extracellular matrix. The cytokine "receptor activator of nuclear factor kappa B ligand" (RANKL), is expressed in stenotic aortic valves and involved in valvular calcification during calcific aortic valve stenosis. The present study aimed to assess the influence of RANKL on the molecular mechanisms of connective tissue remodeling. In an established cell culture model of primary human aortic valve myofibroblasts, stimulation with RANKL increased cell proliferation as compared to medium alone. Matrix metalloproteinase (MMP)-1 was detectable time-dependently in conditioned media from RANKL-stimulated cells, but absent in media from control cells. MMP-1 activity was increased by RANKL, as measured by collagenase activity assay. Zymography showed an increase in active MMP-2 in RANKL-stimulated cells. These results support the concept that MMPs are involved in the connective tissue remodeling during calcific aortic valve stenosis. RANKL might regulate this process by promoting cell proliferation and MMP expression and activation.

Aortic Valve↗
PubMed2005

Plasma L-arginine and metabolites of nitric oxide synthase in patients with left-to-right shunt after intracardiac repair.

STUDY OBJECTIVE: Human plasma L-arginine serves as a substrate pool for endothelial-derived nitric oxide (NO) synthase. In this pilot study, we tested the hypothesis that plasma L-arginine and other metabolites of the L-arginine NO pathway could correlate with postoperative pulmonary hypertension after cardiopulmonary bypass (CPB). DESIGN: Forty-two patients (median age, 0.5 years; range, 0.1 to 28 years) with atrial septal defect (n = 15), ventricular septal defect (n = 18), atrioventricular canal (n = 8), and aortopulmonary window (n = 1) were enrolled. The influence of patient age, preoperative pulmonary hypertension, duration of CPB, plasma L-arginine, guanosine 3', 5'-cyclic monophosphate (cGMP), and nitrate on postoperative pulmonary hypertension during the first 24 h after CPB was studied by logistic regression. RESULTS: Nineteen of 42 patients were found to have preoperative pulmonary hypertension. Thirteen of 42 patients showed persistent pulmonary hypertension after intracardiac repair with a mean pulmonary artery pressure (PAP) of 38 mm Hg (range, 23 to 55 mm Hg) at 24 h after CPB. L-arginine concentrations in plasma were significantly lower 24 h after CPB than before: 52 mumol/L (range, 18 to 95 mumol/L) vs 79 mumol/L (range, 31 to 157 mumol/L). Plasma cGMP levels were higher and plasma nitrate levels were lower immediately after weaning from CPB (p < 0.0033). On logistic regression analysis, only patient age (p = 0.02) and preoperative PAP (p = 0.01) were related to postoperative pulmonary hypertension. CONCLUSION: Low plasma L-arginine does not relate to persistent pulmonary hypertension in patients with left-to-right shunt after CPB and intracardiac repair.

Adolescent↗
PubMed2005

Tumor necrosis factor alpha promotes an osteoblast-like phenotype in human aortic valve myofibroblasts: a potential regulatory mechanism of valvular calcification.

Valvular calcification during calcific aortic stenosis is associated with morphological features of bone formation and expression of various bone-associated proteins, which are both associated with marked leukocyte infiltration of the calcified valve areas. The pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) is abundantly present in areas of leukocyte infiltration in stenotic aortic valves. We therefore hypothesized that valvular calcification might be actively regulated by an inflammatory process involving TNF-alpha. Upon stimulation with TNF-alpha, human aortic valve myofibroblasts cultured under mineralizing conditions showed an increased formation of calcified, alkaline phosphatase (ALP)-enriched cell nodules, ALP activity, concentration of the bone-type ALP isoenzyme, and concentration of osteocalcin, all of which are markers of an osteoblast-like cellular phenotype. By electrophoretic mobility shift assay, DNA binding of the essential osteoblastic transcription factor Cbfa-1 was increased compared to untreated controls. These results support the concept that aortic valve calcification is associated with an osteoblast-like phenotype of local myofibroblasts. In addition, the data demonstrate direct mechanistic evidence that aortic valve calcification may be actively regulated by an inflammatory process involving TNF-alpha.

Aortic Valve↗
PubMed2005

Are there surgical implications to aortic root motion?

BACKGROUND AND AIM OF THE STUDY: By increasing the longitudinal stress in the ascending aorta, downward movement of the aortic root might promote the proximal transverse tears seen in aortic dissections. The study aim was to evaluate the influence of five common cardiac conditions on the magnitude of aortic root displacement in cardiac patients. METHODS: Aortic root contrast injections were analyzed in 90 patients (mean age 68 years) to measure downward motion of the root perpendicular to the plane of the sinotubular junction (STJ). RESULTS: Displacement of the aortic root ranged from 0 to 14 mm (mean 4.8 mm). Patients with aortic insufficiency (AI) showed increased aortic root movement (7.3 versus 4.3 mm, p = 0.003), whereas those with left ventricular hypokinesis (3.7 versus 5.5 mm, p = 0.014) or with myocardial hypertrophy (3.8 versus 5.1 mm, p = 0.073) exhibited reduced downward movement. These variables were independent, and correlated with the magnitude of aortic root motion. A stress analysis of the aortic root, arch and branches of the arch determined that the longitudinal stress approximately 2 cm above the STJ, in the outer curve of the aorta, was increased by 32% in patients with AI compared to patients without AI. CONCLUSION: Patients with cardiac conditions associated with increased aortic root motion such as AI may be at greater risk of aortic dissection because of increased longitudinal stress in the ascending aorta. Therefore, AI should be used as an indicator and aortic root displacement monitored to prevent the risk of aortic dissection.

Adult↗
PubMed2004

Poly(ADP-ribose) polymerase activation in the reperfused myocardium.

The activation of poly(ADP-ribose) polymerase (PARP) is now considered a final common effector in various types of tissue injury including systemic inflammation, circulatory shock and ischemia/reperfusion. Free radical and oxidant production and related cytotoxicity during ischemia/reperfusion leads to DNA strand breakage which activates the nuclear enzyme PARP and initiates an energy-consuming, inefficient cellular metabolic cycle with transfer of the ADP-ribosyl moiety of NAD+ to protein acceptors. During the last 5 years, a growing number of experimental studies demonstrated the beneficial effects of PARP inhibition in cell cultures through rodent models and more recently in pre-clinical large animal models of regional and global ischemia/reperfusion injury. The objective of the current review is to provide an overview of the experimental evidence implicating PARP as a pathophysiological modulator of myocardial injury in vitro and in vivo.

Animals↗
PubMed2004

A case of pulmonary artery sling associated with long-segment funnel trachea and bronchus suis.

An infant with pulmonary sling syndrome associated with an abnormal branching of the trachea, bronchus suis, complicated by long segment intrathoracic tracheal stenosis (ie, "funnel trachea") and concomitant tracheomalacia underwent reoperation at 5 months of age. We review the anatomy of this rare entity and describe the surgical technique to avoid the residual stenosis.

Abnormalities, Multiple↗
PubMed2004

Ventricularization of the atrialized chamber: a concept of Ebstein's anomaly repair.

BACKGROUND: We report results of a technique of Ebstein's anomaly repair by creating a predominantly monocuspid valve with simultaneous ventricularization of the atrialized right ventricular (aRV) chamber. METHODS: Between March 1993 and April 2003, Ebstein's anomaly repair by valvuloplasty with combined ventricularization was performed in 23 patients aged 13.6 (4.1-52.6) years presenting with tricuspid valve regurgitation (TVR) (I degrees, n = 1; II degrees, n = 3; III degrees, n = 13; IV degrees, n = 6). Valvuloplasty consisted of creating a predominantly monocuspid valve at the level of the anatomical atrioventricular junction resulting in a ventricularization of the atrialized chamber. Postoperatively all survivors were examined regularly with an actual prospective evaluation. RESULTS: One early death (4.4%) occurred and was caused by right heart failure. Follow-up was 4.6 (0.5-10.9) years. Important recurrent atrioventricular valve regurgitation caused by rupture of fixation sutures occurred in 3 patients (13%), necessitating reintervention at 3 (0.03-4) months (revalvuloplasty, n = 2; TV replacement, n = 1). One patient presenting with hypoplastic right ventricle with consecutive right heart failure underwent creation of a total cavopulmonary connection at 10 months. At present all patients are doing well. Actual echocardiographic examination revealed significant improvement of right atrioventricular valve regurgitation (p < 0.0001) and favorable restoration of RV geometry and function. CONCLUSIONS: This technique of Ebstein's anomaly repair with ventricularization of the atrialized chamber provides excellent results regarding right atrioventricular valve function and leads to a favorable restoration of RV geometry and function.

Adolescent↗
PubMed2004

The role of platelet derived growth factor in endomyocardial biopsies shortly after heart transplantation in relation to postoperative course.

OBJECTIVE: Platelet-derived growth factor (PDGF) plays an important role in structural alterations of blood vessels after heart transplantation (HTx). The aim of this study was to clarify the effect of peritransplant injury and postoperative complications on the expression of PDGF ligand and receptor. METHODS: Right ventricular endomyocardial biopsies were collected from 46 patients before implantation, and then 1 and 2 weeks after HTx. According to the clinical course in the first postoperative year and to histopathological evaluation (based on the standardised 'International Society for Heart and Lung Transplantation' grading system) three groups were formed: (a) clinical uneventful course; (b) histologically and/or serologically proven cardiac or systemic infections; and (c) acute rejection episodes > or =grade 3A. Both, infections and rejections were detectable after the second postoperative week. The expression of PDGF AA/BB and PDGF receptors alpha/beta was examined immunohistochemically. The infiltrating cells were characterised by using monoclonal antibodies against CD3, CD4, CD8, CD57 and CD68. RESULTS: Only endothelial cells revealed a relevant expression of PDGF ligand and receptor. Prior to implantation there was no or only weak reactivity of single cells for all PDGF factors. One week after HTx a significantly increased immunoreactivity of all PDGF factors was observed in all groups. Two weeks after HTx the expression of PDGF AA in the infection group and the expression of all four PDGF factors in the rejection group remained significantly elevated. In contrast, in the group with an uneventful course there was no statistical difference in the expression of all the four PDGF factors. Compared with the uneventful group, there were significantly more CD3+ cells in the infection and rejection group at all three time points. Two weeks after HTx, the rejection group showed a significantly elevated number of CD3+ cells compared to the values before implantation. Two weeks after HTx there were significant more CD68+ cells in the infection and rejection group compared with before implantation. CONCLUSIONS: One week after HTx the peritransplant injury predominantly influences the endothelial expression of PDGF ligand and receptor. In the first postoperative week, expression of PDGF could be detected. The persistence of evaluated PDGF expression might be of prognostic value in terms of a risk for either infection or rejection. These patients should be carefully monitored.

Adolescent↗
PubMed2004

Role of poly(ADP-ribose) polymerase activation in the pathogenesis of cardiopulmonary dysfunction in a canine model of cardiopulmonary bypass.

OBJECTIVE: To investigate the effects of PARP inhibition on cardiac and pulmonary function during reperfusion in a clinically relevant experimental model of cardiopulmonary bypass. METHODS: Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 min of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or the potent PARP-inhibitor PJ34 (5 mg/kg; n = 6). Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and pulmonary blood flow, vasodilator responses to acetylcholine and sodium-nitroprusside and pulmonary function were also determined. The cardiac and pulmonary activation of PARP was detected by poly(ADP-ribose) immunohistochemistry. RESULTS: Administration of PJ34 led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 min of reperfusion. Coronary blood flow was also significantly higher in the PJ34 treated group (P < 0.05) PJ34 treatment preserved the acetylcholine-induced increases in coronary and pulmonary blood (P < 0.05) Pulmonary function in terms of alveolar arterial oxygen difference was better maintained in the PJ34 treated animals (P < 0.05). Immunohistochemical staining revealed PARP activation after cardiopulmonary bypass in both the heart and lung, which was prevented by PJ34. CONCLUSIONS: PARP inhibition improves the recovery of myocardial and endothelial function after hypothermic cardiac arrest and protects against the development of remote pulmonary injury during cardiopulmonary bypass.

Animals↗
PubMed2004

A new computer model of mitral valve hemodynamics during ventricular filling.

OBJECTIVE: Quantitative description of left ventricular diastolic filling and mitral valve function remains difficult despite advances in echocardiography. The purpose of the present study was to develop a lumped parameter model of left ventricular filling and validate it in porcine trials under physiological conditions and after valve replacement. METHODS: Six animals were instrumented with aortic flow meter, left atrial pressure catheter and combined left ventricular pressure-conductance catheter. The model simulates ventricular and arterial pressures and flows during diastolic filling. Input parameters include maximum mitral valve area, blood viscosity and density, atrial compliance, left ventricular active relaxation characteristics and initial pressure and flow values. The outputs of the model are atrial and ventricular pressure as well as transmitral flow as a function of time. The model primarily consists of a system of four first-order, non-linear ordinary differential equations which were solved with MATLAB software. RESULTS: Left atrial and ventricular pressure data and model flow curves were nearly identical under baseline conditions, during rapid preload reduction by vena caval occlusion and after prosthetic valve replacement. Measured and model based calculation of early diastolic filling volume (E-wave), showed an excellent correlation under all three conditions (r = 0.998, P < 0.0001; r = 0.997, P < 0.0001; r = 0.974, P < 0.0001, respectively) with a mean difference less then two percent. CONCLUSION: The new lumped parameter model of left ventricular filling allows for the first time a detailed simulation of pressure and flow curves in the left heart including transmitral hemodynamics.

Animals↗
PubMed2004

Bronchial artery revascularization restores peribronchial tissue oxygenation after lung transplantation.

With the interruption of the bronchial arteries after lung transplantation, nutritive support is dependent on collateral flow by the pulmonary arteries with desaturated venous blood. Consequently, oxygen deficiency of the peribronchial and dependent lung tissue may occur. Using a canine model for left lung transplantation, we investigated hypoxic peribronchial tissue after conventional lung transplantation and demonstrated restitution of tissue oxygenation after transplantation with bronchial artery revascularization (BAR) (BAR group: Po2 120.4 +/- 28.7 mm Hg; control group Po2 6.8 +/- 2.8; p < 0.001). BAR in lung transplantation protects peribronchial tissue of the transplanted graft from hypoxia in the early phase after reperfusion.

Airway Resistance↗
PubMed2004

Successful thrombolysis after pulmonary embolectomy for persistent massive postoperative pulmonary embolism.

Massive postoperative pulmonary embolism (PE) is associated with a poor prognosis in patients presenting with haemodynamic instability. Since recent surgery is a commonly accepted contraindication for thrombolytic therapy, pulmonary embolectomy is an appropriate therapeutic approach in these patients. If life-threatening symptoms of PE persist after pulmonary embolectomy, however, very few other therapeutic options are available. We report the successful use of locally administered low-dose thrombolysis 2 days after pulmonary embolectomy in a patient with postoperative PE and persistent severe hypoxaemia and pulmonary hypertension. During and after thrombolysis, no bleeding complications occurred. We conclude that low-dose thrombolysis for PE may be considered even in patients who have recently undergone major thoracic and abdominal surgery if embolectomy and continued intravenous heparin have failed to be successful and life-threatening symptoms of PE persist.

Aged↗
PubMed2004

Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulate aortic valve calcification.

OBJECTIVE: - Recent studies have suggested that valvular calcification in calcific aortic stenosis (AS) may be actively regulated. "Receptor Activator of Nuclear factor kappaB Ligand" (RANKL) and osteoprotegerin (OPG) are members of a cytokine system involved in bone turnover and vascular calcification. Their role in calcific AS is not known. METHODS AND RESULTS: - By immunohistochemistry using human aortic valves, RANKL was not expressed at relevant levels in controls but detectable in AS. OPG expression was marked in controls but significantly lower in AS. Areas containing focal calcification exhibited significantly less OPG-positive cells as compared to non-calcified regions. Stimulation with RANKL lead to a significant rise in matrix calcification, nodule formation, alkaline phosphatase activity, expression of the bone-type isoenzyme of alkaline phosphatase, and expression of osteocalcin in cultured human aortic valve myofibroblasts. Moreover, RANKL increased DNA binding of the essential osteoblast transcription factor cbfa-1. CONCLUSION: - RANKL and OPG are differentially expressed in calcific AS. In cultured human aortic valve myofibroblasts, RANKL promotes matrix calcification and induces the expression of osteoblast-associated genes, indicating a transition towards an osteogenic phenotype. These results suggest that the RANKL-OPG pathway may regulate valvular calcification in calcific AS?

Aortic Valve↗