ACURATE neo2 Versus SAPIEN 3 Ultra Transcatheter Heart Valve in Severe Aortic Valve Calcification: A Propensity-Matched Analysis.

BACKGROUND: Comparative data on transcatheter self-expanding ACURATE neo2 (NEO2) and balloon-expandable SAPIEN 3 Ultra prostheses in technically challenging anatomy of severe aortic valve calcified aortic annuli are scarce. METHODS: A total of 1987 patients with severe native aortic stenosis treated with the self-expanding NEO2 (n=1457) or balloon-expandable SAPIEN 3 Ultra (n=530) from January 2017 to April 2023 were evaluated. The primary end point was procedural outcome according to the Valve Academic Research Consortium 3 definitions. Propensity matching defined 219 pairs with severe calcification (calcium density cutoff, 758 AU/cm2) of the native aortic valve. RESULTS: Technical success (90.4% versus 91.8%; risk difference, 1.4% [95% CI, -4.4 to -7.2]; P=0.737) and device success at 30 days (80.8% versus 75.8%; risk difference, -5.0% [95% CI, -13.2 to 3.1]; P=0.246) were comparable between NEO2 and SAPIEN 3 Ultra. The rate of severe prosthesis-patient mismatch (1.1% versus 10.1%; risk difference, 10.0% [95% CI, 4.0-13.9]; P<0.001) and mean transvalvular gradient ≥20 mm Hg (2.8% versus 14.3%; risk difference, 11.5% [95% CI, 5.8-17.1]; P<0.001) was lower with NEO2. The rate of more-than-mild paravalvular leakage or valve-in-valve due to paravalvular leakage was significantly higher (6.2% versus 0.0%; risk difference, 6.2% [95% CI, -10.1 to -2.7]; P=0.002), and there was a tendency for a higher rate of device embolization or migration (1.8% versus 0.0%; risk difference, -1.8% [95% CI, -4.1 to 0.4]; P=0.123) with NEO2. Multivarate regression revealed no independent impact of transcatheter heart valve selection on device success (odds ratio, 0.93 [95% CI, 0.48-1.77]; P=0.817). CONCLUSIONS: In patients with severely calcified annuli, supraannular implantation of NEO2 showed hemodynamic advantages. Nevertheless, NEO2 was associated with a higher incidence of relevant paravalvular leakage and a numerically higher rate of device embolization than SAPIEN 3 Ultra in this particular patient group.

Left ventricular reverse remodeling after transcatheter aortic valve implantation in patients with low-flow low-gradient aortic stenosis.

OBJECTIVES: Left ventricular reverse remodeling (LVRR) is associated with improved outcome in patients with heart failure. Factors associated with and predictive of LVRR in patients with low-flow low-gradient aortic stenosis (LFLG AS) after transcatheter aortic valve implantation (TAVI) and its impact on outcome were assessed. METHODS: Pre- and postprocedural left ventricular (LV) function and volume were investigated in 219 patients with LFLG. LVRR was defined as an absolute increase of ≥10% in LV ejection fraction (LVEF) and reduction of ≥15% in LV end-systolic volume (LVESV). The primary endpoint was the combination of all-cause mortality and rehospitalization for heart failure. RESULTS: The mean LVEF was 35.0 ± 10.0%, with a stroke volume index (SVI) of 25.9 ± 6.0 mL/m2 and LVESV of 94.04 ± 46.0 mL. At a median of 5.2 months (interquartile range, 2.7-8.1 months), 77.2% (n = 169) of the patients showed echocardiographic evidence of LVRR. A multivariate model revealed three independent factors for LVRR after TAVI: SVI of <25 mL/m2 (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.08-3.58; p < 0.01), LVEF of <30% (HR, 2.76; 95% CI, 1.53-2.91; p < 0.01), and valvulo-arterial impedance (Zva) of <5 mmHg/mL/m2 (HR, 5.36; 95% CI, 1.80-15.98; p < 0.01). Patients without evidence of LVRR showed a significantly higher incidence of the 1-year combined endpoint (32 [64.0%] vs. 75 [44.4%], p < 0.01). CONCLUSIONS: The majority of patients with LFLG AS show LVRR after TAVI, which is associated with favorable outcomes. An SVI of <25 mL/m2, LVEF of <30%, and Zva < 5mmHg/mL/m2 represent predictors of LVRR.

Prevalence of sleep-disordered breathing in patients with mitral regurgitation and the effect of mitral valve repair.

PURPOSE: The relationship between chronic heart failure and sleep-disordered breathing (SDB) has been frequently described. However, little is known about the association of mitral regurgitation (MR) and SDB or the impact of transcatheter mitral valve repair (TMVR) on SDB. Our aims were first to determine the prevalence of SDB in patients with MR, and second to determine the effect of TMVR on SDB. METHODS: Patients with MR being evaluated for TMVR at the University Hospital Bonn underwent polygraphy (PG) to determine the prevalence of SDB. After TMVR, a subset of patients was followed up with transthoracic echocardiography (TTE) and PG to evaluate the effect of TMVR on SDB. RESULTS: In 53 patients, mean age was 76.0 ± 8.5 years and 62% were male. Patients predominantly had more than moderate mitral regurgitation (94%). SDB was highly prevalent (68%) with predominantly central sleep apnoea (CSA, 67%). After TMVR in 15 patients, the apnoea/hypopnoea index (AHI) and central apnoea index (AI) were significantly reduced among patients with SDB (AHI - 8.0/h, p = 0.021; central AI - 6.9/h, p = 0.046). The left atrial volume index (LAVI) at baseline was significantly higher in patients with CSA than in patients with obstructive sleep apnoea (OSA) and was significantly reduced after TMVR (63.5 ml/m2 ± 27.2 vs. 38.3 ml/m2 ± 13.0; - 18.4 ml/m2, p = 0.027). CONCLUSION: SDB, especially CSA, is highly prevalent in patients with mitral regurgitation. In the follow-up cohort TMVR led to a significant reduction of the AHI, predominantly of central events. The findings of the study suggest that TMVR may be a suitable therapy not only for MR but also for the accompanying CSA. LAVI may be a useful indicator for CSA in patients with MR.

Circulating MicroRNA-122-5p Is Associated With a Lack of Improvement in Left Ventricular Function After Transcatheter Aortic Valve Replacement and Regulates Viability of Cardiomyocytes Through Extracellular Vesicles.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis. A majority of patients exhibit improvements in left ventricular ejection fraction (LVEF) after TAVR in response to TAVR-associated afterload reduction. However, a specific role for circulating microRNAs (miRNAs) in the improvement of cardiac function for patients after TAVR has not yet been investigated. Here, we profiled the differential expression of miRNAs in circulating extracellular vesicles (EVs) in patients after TAVR and, in particular, the novel role of circulating miR-122-5p in cardiomyocytes. METHODS: Circulating EV-associated miRNAs were investigated by use of an unbiased Taqman-based human miRNA array. Several EV miRNAs (miR-122-5p, miR-26a, miR-192, miR-483-5p, miR-720, miR-885-5p, and miR-1274) were significantly deregulated in patients with aortic valve stenosis at day 7 after TAVR compared with the preprocedural levels in patients without LVEF improvement. The higher levels of miR-122-5p were negatively correlated with LVEF improvement at both day 7 (r=-0.264 and P=0.015) and 6 months (r=-0.328 and P=0.0018) after TAVR. RESULTS: Using of patient-derived samples and a murine aortic valve stenosis model, we observed that the expression of miR-122-5p correlates negatively with cardiac function, which is associated with LVEF. Mice with graded wire injury-induced aortic valve stenosis demonstrated a higher level of miR-122-5p, which was related to cardiomyocyte dysfunction. Murine ex vivo experiments revealed that miR-122-5p is highly enriched in endothelial cells compared with cardiomyocytes. Coculture experiments, copy-number analysis, and fluorescence microscopy with Cy3-labeled miR-122-5p demonstrated that miR-122-5p can be shuttled through large EVs from endothelial cells into cardiomyocytes. Gain- and loss-of-function experiments suggested that EV-mediated shuttling of miR-122-5p increases the level of miR-122-5p in recipient cardiomyocytes. Mechanistically, mass spectrometry, miRNA pulldown, electrophoretic mobility shift assay, and RNA immunoprecipitation experiments confirmed that miR-122-5p interacts with the RNA-binding protein hnRNPU (heterogeneous nuclear ribonucleoprotein U) in a sequence-specific manner to encapsulate miR-122-5p into large EVs. On shuttling, miR-122-5p reduces the expression of the antiapoptotic gene BCL2 by binding to its 3' untranslated region to inhibit its translation, thereby decreasing the viability of target cardiomyocytes. CONCLUSIONS: Increased levels of circulating proapoptotic EV-incorporated miR-122-5p are associated with reduced LVEF after TAVR. EV shuttling of miR-122-5p regulates the viability and apoptosis of cardiomyocytes in a BCL2-dependent manner.

Latest Advances in Transcatheter Aortic Valve Implantation (2022).

Since the last decade, transcatheter aortic valve implantation (TAVI) has become the treatment of choice in patients with symptomatic severe aortic stenosis (AS) who are ineligible or at higher risk for surgery. Due to the high safety profile of current device generation, TAVI has emerged as a qualified alternative to surgical aortic valve replacement (SAVR) in patients with classic aortic stenosis and intermediate surgical risk, severe bicuspid aortic valve stenosis, and isolated pure aortic regurgitation. Moderate aortic stenosis, with and without concomitant heart failure with reduced ejection fraction, are under investigation in randomized controlled clinical trials from which we will gain exciting insights on the best timing of TAVI to protect the left ventricle from further functional deterioration due to increasing AS. In these cases, a meticulous diagnostic approach including advanced imaging is becoming more and more important. Current evidence on antithrombotic strategies after TAVI is weak, contributing to poor levels of standardization and high variability in daily clinical practice. This review will provide a short overview of recent clinical trials including best timing for TAVI with moderate AS and antithrombotic strategies after TAVI with current and future TAVI generations.

A novel scoring system to estimate chemotherapy-induced myocardial toxicity: Risk assessment prior to non-anthracycline chemotherapy regimens.

BACKGROUND: Myocardial toxicity is a common side effect of chemotherapy and is associated with adverse outcomes in cancer patients. Sufficient prediction of chemotherapy-induced myocardiotoxicity (CIMC) is desirable. Therefore, we sought to develop a feasible scoring system to predict CIMC in cancer patients undergoing non-anthracycline chemotherapy. METHODS: We determined a scoring system, the "Cardiotoxicitiy Score" (the CardTox-Score), by multivariable regression of the parameters considered relevant to the development of CIMC, based on previously published data and current guidelines. Variables of the risk model consist of clinical (age, presence of cardiovascular risk conditionsconditions), blood tests (NT-proBNP), and echocardiographic parameters (left ventricular (LV) ejection fraction, LV strain analysis). The CardTox-Score was examined in an internal validation cohort by use of ROC and regression analysis. RESULTS: We prospectively investigated 225 patients (58.21 ± 6.3 years, 52.8% female) who received non-anthracycline myocardiotoxic anticancer agent as a derivation cohort. All patients underwent echocardiography before, during and after anticancer therapy. The mean follow-up duration was 25 ± 4 months. We found the CardTox-Score (>6 points) to be a strong independent predictor (AUC: 0.983, OR: 6.38, 95% CI: 1.6 2.8, p < 0.001) for the development of CIMC with high sensitivity (100%) and specificity (84.2%) in the validation cohort (n = 30, 59.2 ± 6.5 years, 57% female). Moreover, the CardTox-Score appropriately predicted all-cause mortality with high specificity (93.7%) and sensitivity (92.9%) as well (OR: 4.85, AUC: 0.978, p = 0.01). CONCLUSION: The CardTox-Score offers a promising, feasible, and easy-to-handle scoring system for predicting CIMC in cancer patients undergoing non-anthracycline regimes, independent from the type of cancer.

Risk of mortality following transcatheter aortic valve replacement for low-flow low-gradient aortic stenosis.

BACKGROUND: Low-flow low-gradient (LF-LG) aortic stenosis (AS) is associated with high mortality, even after transcatheter aortic valve replacement (TAVR). Further knowledge of risk indicators is needed and a clinical risk score would be desirable for optimizing patient selection and therapeutic strategy. METHODS: The study cohort comprised of 219 consecutive LF-LG AS patients undergoing TAVR from 2008 to 2018 in two high-volume German centers. Predictive factors for one-year all-cause mortality were defined according to a Cox proportional hazard model. RESULTS: At one-year follow-up after TAVR, 28% of patients had died. A multivariate model revealed six independent predictors of one-year mortality: history of myocardial infarction (HR 2.05, 95%CI 1.13-3.72), eGFR < 30 ml/min/1.73m2 (HR 2.75, 95%CI 1.48-5.11), tricuspid regurgitation moderate or more (HR 2.06, 95%CI 1.14-3.72), stroke volume index < 25 mL/m2 (HR 2.03, 95%CI 1.14-3.62), self-expandable device (HR 2.72, 95%CI 1.17-6.27), and non-transfemoral approach (HR 3.42, 95%CI 1.28-9.14). The Rhineland Risk Score (RRS) consisting of these variables (c statistic 0.75, 95%CI 0.68-0.82, p < 0.001) was superior to the EuroSCORE II (c statistic 0.63) and STS-PROM score (c statistic 0.69) at predicting one-year mortality. Patients with a RRS ≥ 8 had a prohibitive risk of one-year mortality of 67.6% (95%CI 52.0-82.4%). CONCLUSION: In patients with LF-LG AS, history of myocardial infarction, renal dysfunction, tricuspid regurgitation, a low stroke volume index, self-expandable device, and non-femoral approach were associated with increased 1-year mortality after TAVR. The RRS might serve as a helpful tool for risk prediction and patient selection for TAVR in patients with LF-LG AS.

Pulmonary capillary wedge pressure (PCWP) as prognostic indicator in patients undergoing transcatheter valve repair (TTVR) of severe tricuspid regurgitation.

BACKGROUND: TTVR represents a minimal invasive alternative for patients with tricuspid regurgitation (TR). PCWP is a haemodynamic parameter indicating pulmonary hypertension due to left-sided heart failure. METHODS: We evaluated pulmonary capillary wedge pressure (PCWP) as prognostic outcome parameter in patients undergoing transcatheter tricuspid valve repair (TTVR). A total of 60 patients who underwent right heart catheterization prior to TTVR were included. Patient population was categorized into a low and high PCWP group according to the median PCWP of 16 mmHg. RESULTS: TTVR included transcatheter tricuspid annuloplasty (13 patients) and edge-to-edge repair [37 patients for isolated TR; 10 patients for combined TR and mitral regurgitation]. Kaplan-Meier analysis and log-rank test revealed reduced 6-months event-free survival for patients with high PCWP (>16 mmHg) in comparison to those with low PCWP (≤16 mmHg) (p = 0.009). High PCWP was associated with increased occurrence of the composite endpoint of death and cardiac readmission (HR 4.67, 1.32-16.55). Moreover, adjusted with other predictive variables within the univariate analysis (left ventricular ejection fraction, history of smoking, tricuspid annular plane systolic excursion), PCWP remained an endpoint predictor (HR 1.11, 1.003-1.24). Best predicting value was evaluated for the cut-off >16 mmHg (AUC 0.700, 0.552-0.848). Patients with a high PCWP tended to have less TR recurrence (p = 0,059) and lower NYHA class (p = 0.062) after one month of follow-up. CONCLUSION: Here we demonstrate that PCWP is a predictive outcome parameter in TTVR patients. Patients with a PCWP ≤16 mmHg had a favourable outcome with lower mortality and morbidity gaining more benefit of TTVR.

Endocannabinoid 2-arachidonoylglycerol is elevated in the coronary circulation during acute coronary syndrome.

OBJECTIVES: The endocannabinoid system modulates coronary circulatory function and atherogenesis. The two major endocannabinoids (eCB), 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamide (AEA), are increased in venous blood from patients with coronary artery disease (CAD). However, given their short half-life and their autocrine/paracrine mechanism of action, eCB levels in venous blood samples might not reflect arterial or coronary eCB concentrations. The aim of this cross-sectional study was to identify the local concentration profile of eCB and to detect whether and how this concentration profile changes in CAD and NSTEMI versus patients without CAD. METHODS AND RESULTS: 83 patients undergoing coronary angiography were included in this study. Patients were divided into three groups based on their definite diagnosis of a) no CAD, b) stable CAD, or c) non-ST-segment elevation myocardial infarction (NSTEMI). Blood was drawn from the arterial sheath and the aorta in all patients and additionally distal to the culprit coronary lesion in CAD- and NSTEMI patients. 2-AG levels varied significantly between patient groups and between the sites of blood extraction. The lowest levels were detected in patients without CAD; the highest 2-AG concentrations were detected in NSTEMI patients and in the coronary arteries. Peripheral 2-AG levels were significantly higher in NSTEMI patients (107.4 ± 28.4 pmol/ml) than in CAD- (17.4 ± 5.4 pmol/ml; p < 0.001), or no-CAD patients (23.9 ± 7.1 pmol/ml; p < 0.001). Moreover, coronary 2-AG levels were significantly higher in NSTEMI patients than in CAD patients (369.3 ± 57.2 pmol/ml vs. 240.1 ± 25.3 pmol/ml; p = 0.024). CONCLUSIONS: 2-AG showed significant variability in arterial blood samples drawn from distinct locations. Possibly, lesional macrophages synthesise 2-AG locally, which thereby contributes to endothelial dysfunction and local inflammation.

Anti-atherosclerotic effects of serelaxin in apolipoprotein E-deficient mice.

BACKGROUND AND AIMS: Serelaxin (SLX) is a recombinant form of human relaxin-2, a naturally occurring peptide that regulates maternal cardiovascular adaptations to pregnancy. It is unclear whether SLX has a therapeutic effect on atherosclerosis. Therefore, we investigated direct vascular effects of SLX in a mouse model of atherosclerosis. METHODS: 6-8 week-old female apolipoprotein E-deficient mice were fed a high-fat, cholesterol-rich diet for 6 weeks and additionally received a continuous treatment with vehicle or SLX (0.05 or 0.1 µg/h), during the last 4 weeks, via subcutaneously implanted osmotic mini-pumps. Vascular oxidative stress, vasorelaxation and atherosclerotic plaque development were assessed. RESULTS: Vascular oxidative stress was reduced in SLX-treated mice (vehicle: 322.67 RLU/s, SLX 0.05 µg/h: 119.76 RLU/s (p < 0.001 vs. vehicle), SLX 0.1 µg/h: 109.33 RLU/s (p < 0.001 vs. vehicle; p = 0.967 vs. 0.05 µg/h SLX)). Further SLX improved endothelium-dependent vasodilatation without influencing endothelium-independent vasorelaxation. Atherosclerotic plaque development was significantly reduced by SLX (vehicle: 0.38 ± 0.02 mm(2), 0.05 µg/h SLX: 0.32 ± 0.02 mm(2) (p = 0.047 vs. vehicle), 0.1 µg/h SLX: 0.29 ± 0.02 mm(2) (p = 0.002 vs. vehicle; p = 0.490 vs. 0.05 µg/h SLX)). Neither vascular macrophage, T-cell or neutrophil infiltration, nor collagen/vascular smooth muscle cell content differed between the groups. We observed a significant down-regulation of the angiotensin II type 1a receptor and a decrease in IL-6 and an increase in IL-10 plasma concentrations. CONCLUSIONS: Our data demonstrates novel pleiotropic effects of SLX on vascular oxidative stress, endothelial dysfunction and atherosclerotic plaque burden. Therefore, SLX could serve as a new drug for the treatment of atherosclerosis-related diseases.

Catch of the day: interventional device retrieval after late embolization of an Amplatzer cardiac plug left atrial appendage occluder.

Transcatheter left atrial appendage (LAA) closure has proven to be an effective method to reduce the risk of thromboembolic events in patients who have nonvalvular atrial fibrillation (AF) that is unsuitable for chronic oral anticoagulation. In this case report, we describe the rare case of a late LAA occluder (28-mm Amplatzer cardiac plug) embolization, which was treated uneventfully with interventional device capture. Special interventional and device specific characteristics must be taken into account when planning such a complex procedure as described in our case.

Influence of smoking dosage and chronic obstructive lung disease on the incidence of appropriate therapies and mortality in patients with structural heart disease and an implantable cardioverter defibrillator.

BACKGROUND: Smoking is known as a relevant risk factor for severe cardiac morbidities and mortality. This study was initiated to explore the influence of smoking dosage and presence of chronic obstructive lung disease (COPD) on the incidence of appropriate implantable cardioverter defibrillator (ICD) interventions and on mortality. METHODS: Prior studies on patients equipped with an ICD suggested that nicotine consumption increases the risk of experiencing an appropriate ICD therapy. There is no substantial data regarding the influence of cigarette smoking dosage on overall mortality in such endangered patients. A total of 349 patients with structural heart disease, either coronary artery disease or nonischemic cardiomyopathy equipped with an ICD, were included. Every patient answered a questionnaire regarding his smoking status and performed a spirometry and body plethysmography. RESULTS: A total of 104 patients (30%) suffered from COPD. Fifty-eight patients (17%) were "current smokers," 196 patients (56%) were revealed as "former smokers," while 93 (27%) patients were registered as "never smokers." A total of 163 patients (47%) received at least one appropriate ICD intervention during follow-up (median 48 ± 8 months). Twenty-three patients died during this study (6.6%). There was no association of COPD with the incidence of appropriate ICD therapies or mortality. Smoking dosage revealed as a significant risk factor for both appropriate ICD interventions (hazard ratio [HR] 1.5 for 60 pack years [PY] P = 0.04) and mortality (HR 2.3 for 60 PY P = 0.02). CONCLUSION: This study demonstrates a dose-related increased risk of smokers for appropriate ICD interventions and mortality. The results of this trail urge a strict nicotine abstinence, especially in patients with a structural heart disease undergoing ICD therapy.

Interleukin-6 is the strongest predictor of 30-day mortality in patients with cardiogenic shock due to myocardial infarction.

INTRODUCTION: Cardiogenic shock (CS) remains the leading cause of death in patients hospitalized for myocardial infarction (MI). Systemic inflammation with inappropriate vasodilatation is observed in many patients with CS and may contribute to an excess mortality rate. The purpose of this study was to determine the predictive role of serial measurements of Nt-proBNP, interleukin-6 (IL-6), and procalcitonin (PCT) for 30-day mortality in patients with CS due to MI. METHODS: The present study is a prospective single-center study including 87 patients with MI complicated by CS treated with acute revascularization and intraaortic balloon counterpulsation (IABP) support. Predictive values of plasma levels at admission (T0), after 24 hours (T1), and after 72 hours (T2) were examined according to 30-day mortality. RESULTS: Significant differences between survivors (n = 59) and nonsurvivors (n = 28) were seen for Nt-proBNP at T0, for IL-6 at T0 and T1, and for PCT at T1 and T2. According to ROC analyses, the highest accuracy predicting 30-day mortality was seen at T0 for IL-6, at T1 for PCT, and at T2 for PCT. In univariate analysis, significant values were found for Nt-proBNP at T1, and for IL-6 and PCT at all points in time. Within the multivariate analysis, age, creatinine, and IL-6 were significant determinants of 30-day mortality, in which IL-6 showed the highest level of significance. CONCLUSIONS: In patients with MI complicated by CS, IL-6 represented a reliable independent early prognostic marker of 30-day mortality. PCT revealed a significant value at later points in time, whereas Nt-proBNP seemed to be of lower relevance.

Estrogen improves vascular function via peroxisome-proliferator-activated-receptor-γ.

The exact mechanism of estrogen in cardiovascular disease is not fully understood. As estrogen receptors (ERs), the peroxisome-proliferator-activated-receptor-γ (PPARγ) belongs to the family of ligand activated nuclear receptors regulating atheroprotective genes. The aim of this project was to investigate whether vascular effects of estrogen are mediated via PPARγ-regulation in the vascular compartment. Estrogen deficient ovariectomized wildtype-mice (OVX) displayed significant reduction of PPARγ-expression in aortic tissue compared to wildtype-mice with intact ovarian function (Sham). Hormone replacement with subdermal 17ß-estradiol pellets significantly increased vascular PPARγ-expression in ovariectomized female wildtype-mice (OVX/E2). Analogous to wildtype-mice, estrogen-deficient OVX ApoE(-/-)-mice had low vascular PPARγ-expression associated with ROS generation, endothelial dysfunction and atherogenesis. Estrogen replacement (OVX/E2) rescued vascular PPARγ-expression, reduced ROS generation, monocyte recruitment, atherosclerotic lesion formation and improved endothelial function. Inhibition of PPARγ by GW9662, a specific PPARγ-antagonist reduced 17ß-estradiol mediated vascular effects (OVX/E2+GW9662). Finally, despite estrogen deficiency treatment with pioglitazone (OVX+pioglitazone), a selective PPARγ-agonist, compensates deterioration of vascular morphology and function. 17ß-estradiol regulates vascular PPARγ-expression in wildtype- and ApoE(-/-)-mice. The presented data demonstrate the fundamental relevance of PPARγ as downstream target of 17ß-estradiol-related anti-inflammatory and atheroprotective effects within the vascular wall independent of its cardiovascular risk factor modifications.