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Severin P. Schwarzacher

Bio: Severin P. Schwarzacher is an academic researcher from University of Innsbruck. The author has contributed to research in topics: Intravascular ultrasound & Vascular endothelial growth factor. The author has an hindex of 26, co-authored 57 publications receiving 2637 citations. Previous affiliations of Severin P. Schwarzacher include University of Vienna & Stanford University.


Papers
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Journal ArticleDOI
TL;DR: The present findings suggest that the impairment of FMD in the brachial artery, a marker of systemic endothelial function, is closely related to the angiographic extent of CAD.

535 citations

Journal ArticleDOI
TL;DR: Findings support the concept that statins have antiinflammatory and antiproliferative effects that are relevant in the treatment of atherosclerotic diseases.
Abstract: Objective— Pleiotropic atheroprotective effects of HMG-CoA reductase inhibitors may be mediated on the level of vascular gene transcription. The aim of this study was to characterize the effects of statins on the activation of transcription factors known to regulate inflammation and cell proliferation/differentiation. Methods and Results— Simvastatin, atorvastatin, and lovastatin (0.1 to 10 μmol/L) inhibited the binding of nuclear proteins to both the nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) DNA consensus oligonucleotides in human endothelial and vascular smooth muscle cells as assessed by electrophoretic mobility shift assay (EMSA). The inhibitory effects of statins on NF-κB or AP-1–dependent transcriptional activity were examined by transient transfection studies. HMG-CoA reductase inhibitors upregulated IκB-α protein levels in endothelial cells and decreased c-Jun mRNA expression in smooth muscle cells as analyzed by Western and Northern blotting, respectively. Furthermore, statins inhibited DNA binding of hypoxia-inducible factor-1α. Downstream effects of statins included inhibition of plasminogen activator inhibitor-1 and vascular endothelial growth factor-A mRNA levels in endothelial cells. Conclusions— HMG-CoA reductase inhibitors downregulate the activation of transcription factors NF-κB, AP-1, and hypoxia-inducible factor-1α. These findings support the concept that statins have antiinflammatory and antiproliferative effects that are relevant in the treatment of atherosclerotic diseases.

325 citations

Journal ArticleDOI
TL;DR: On comparison with angiography, the vast majority of stents associated with subsequent thrombosis have at least one abnormal feature by intravascular ultrasound at the time of stent deployment.
Abstract: Aims To investigate whether intravascular ultrasound provides additional information regarding the prediction of stent thrombosis, a retrospective multicentre registry was designed to enrol patients with stent thrombosis following stent deployment under ultrasound guidance. Methods and Results A total of 53 patients were enrolled (mean age 61±9 years) with stable angina (43%), unstable angina (36%), and post-infarct angina (21%) who underwent intracoronary stenting. The majority had balloon angioplasty alone prior to stenting (94%) with 6% also undergoing rotational atherectomy. The indication for stenting was elective (53%), suboptimal result (32%) and bailout (15%). There were 1·6±0·8 stents/artery with 87% undergoing high-pressure dilatation (≥14 atmospheres). The minimum stent area was 7·7±2·8mm2with a mean stent expansion of 81·5±21·9%. Overall, 94% of cases demonstrated one abnormal ultrasound finding (stent under-expansion, malapposition, inflow/outflow disease, dissection, or thrombus). Angiography demonstrated an abnormality in only 32% of cases (chi-square=30·0, P <0·001). Stent thrombosis occurred at 132±125h after deployment. Myocardial infarction occurred in 67% and there was an overall mortality of 15%. Conclusion On comparison with angiography, the vast majority of stents associated with subsequent thrombosis have at least one abnormal feature by intravascular ultrasound at the time of stent deployment.

249 citations

Journal ArticleDOI
TL;DR: Results indicate that supplemental L-arginine induces apoptosis of macrophages in intimal lesions by its metabolism to NO, which acts through a cGMP-independent pathway, consistent with previous observation that supplementation of dietary arginine induces regression of atheroma in this animal model.
Abstract: Background—We have recently found that administration of l-arginine to hypercholesterolemic rabbits induces regression of preexisting lesions. Others have previously shown that activation of the l-arginine/nitric oxide (NO) synthase pathway can induce apoptosis of vascular cells in vitro. Accordingly, the current study was designed to determine if dietary supplementation of l-arginine induces apoptosis of intimal lesions and if this effect is mediated through the NO synthase pathway. Methods and Results—Male New Zealand White rabbits were fed a 0.5% cholesterol diet for 10 weeks and subsequently placed on 2.5% l-arginine HCl in the drinking water, and the cholesterol diet was continued for 2 weeks, at which time the aortas were harvested for histological studies. l-Arginine treatment increased the number of apoptotic cells (largely macrophages) in the intimal lesions by 3-fold (11.9±3.9 vs 3.9±1.4 apoptotic cells/mm2, P<0.01). In subsequent studies, aortas were harvested for ex vivo studies. Aortic segmen...

170 citations

Journal ArticleDOI
TL;DR: In this article, biochemical evidence was provided that ultra-endurance exercise may cause subclinical myocardial damage, even in well-trained cyclists, and the cellular nature of this damage and its clinical relevance remain unknown at present.
Abstract: This study provides biochemical evidence that ultraendurance exercise may cause subclinical myocardial damage, even in well-trained cyclists. The cellular nature of this damage and its clinical relevance remain unknown at present.

134 citations


Cited by
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Journal ArticleDOI
TL;DR: The targeted suppression of various proinflammatory cascades in adipocytes specifically represents an exciting new therapeutic opportunity for the cardiovascular disease area.
Abstract: Mounting evidence highlights the role of adipose tissue in the development of a systemic inflammatory state that contributes to obesity-associated vasculopathy and cardiovascular risk. Circulating mediators of inflammation participate in the mechanisms of vascular insult and atheromatous change, and many of these inflammatory proteins are secreted directly from adipocytes and adipose tissue-derived macrophages. Several factors linking obesity with an increased cardiovascular risk have been identified. The adipocyte-specific secretory protein adiponectin is a particularly promising candidate in this context. Its levels are decreased in obesity. Adiponectin may mediate some of its demonstrated cardioprotective effects through its anti-inflammatory properties. In addition to decreased expression of beneficial adipokines, secretion of a host of inflammatory factors from visceral adipose tissue may contribute to the increased cardiovascular risk associated with obesity. The cardioprotective effects of many of the most popular drug regimens corroborate these conclusions, demonstrating that along with improvements in other therapeutic end points, they mediate improvements in systemic inflammation. In some cases, these improvements are attributable to direct suppression of inflammatory signaling in adipocytes. The targeted suppression of various proinflammatory cascades in adipocytes specifically represents an exciting new therapeutic opportunity for the cardiovascular disease area.

1,946 citations

Journal ArticleDOI
TL;DR: Data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity, and predict the risk of cardiovascular events in patients with coronary arteries disease.
Abstract: Background Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations. Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events. This study was designed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease. Methods and Results Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography. The effect of the coadministration of vitamin C (24 mg/min) was assessed in a subgroup of 179 patients. Cardiovascular events, including death from cardiovascular causes, myocardial infarction, ischemic stroke, coronary angioplasty, and coronary or peripheral bypass operation...

1,903 citations

Journal ArticleDOI
TL;DR: In this paper, HDL has been shown to have anti-atherogenic properties, which may explain the ability of HDL to promote the efflux of cholesterol from cells in the artery wall.
Abstract: There are several well-documented functions of high-density lipoprotein (HDL) that may explain the ability of these lipoproteins to protect against atherosclerosis. The best recognized of these is the ability of HDL to promote the efflux of cholesterol from cells. This process may minimize the accumulation of foam cells in the artery wall. However, HDL has additional properties that may also be antiatherogenic. For example, HDL is an effective antioxidants. The major proteins of HDL, apoA-I and apoA-II, as well as other proteins such as paraoxonase that cotransport with HDL in plasma, are well-known to have antioxidant properties. As a consequence, HDL has the capacity to inhibit the oxidative modification of low-density lipoprotein (LDL) in a process that reduces the atherogenicity of these lipoproteins. HDL also possesses other antiinflammatory properties. By virtue of their ability to inhibit the expression of adhesion molecules in endothelial cells, they reduce the recruitment of blood monocytes into the artery wall. These antioxidant and antiinflammatory properties of HDL may be as important as its cholesterol efflux function in terms of protecting against the development of atherosclerosis.

1,241 citations

Journal ArticleDOI
Ira Tabas1
TL;DR: This Review provides an overview of concepts, with a focus on macrophage death and defective apoptotic cell clearance, and discusses new therapeutic strategies designed to boost inflammation resolution in atherosclerosis.
Abstract: A key event in atherosclerosis is a maladaptive inflammatory response to subendothelial lipoproteins. A crucial aspect of this response is a failure to resolve inflammation, which normally involves the suppression of inflammatory cell influx, effective clearance of apoptotic cells and promotion of inflammatory cell egress. Defects in these processes promote the progression of atherosclerotic lesions into dangerous plaques, which can trigger atherothrombotic vascular disease, the leading cause of death in industrialized societies. In this Review I provide an overview of these concepts, with a focus on macrophage death and defective apoptotic cell clearance, and discuss new therapeutic strategies designed to boost inflammation resolution in atherosclerosis.

1,022 citations

Journal ArticleDOI
TL;DR: Given the strong prognostic links between vascular structure, function and cardiovascular events, the implications of these findings are obvious, yet many unanswered questions remain, including the mechanisms responsible for NO bioactivity, the nature of the cellular effect and relevance of other autacoids, but also such practical questions as the optimal intensity, modality and volume of exercise training required in different populations.
Abstract: Vascular endothelial function is essential for maintenance of health of the vessel wall and for vasomotor control in both conduit and resistance vessels. These functions are due to the production of numerous autacoids, of which nitric oxide (NO) has been the most widely studied. Exercise training has been shown, in many animal and human studies, to augment endothelial, NO-dependent vasodilatation in both large and small vessels. The extent of the improvement in humans depends upon the muscle mass subjected to training; with forearm exercise, changes are restricted to the forearm vessels while lower body training can induce generalized benefit. Increased NO bioactivity with exercise training has been readily and consistently demonstrated in subjects with cardiovascular disease and risk factors, in whom antecedent endothelial dysfunction exists. These conditions may all be associated with increased oxygen free radicals which impact on NO synthase activity and with which NO reacts; repeated exercise and shear stress stimulation of NO bioactivity redresses this radical imbalance, hence leading to greater potential for autacoid bioavailability. Recent human studies also indicate that exercise training may improve endothelial function by up-regulating eNOS protein expression and phosphorylation. While improvement in NO vasodilator function has been less frequently found in healthy subjects, a higher level of training may lead to improvement. Regarding time course, studies indicate that short-term training increases NO bioactivity, which acts to homeostatically regulate the shear stress associated with exercise. Whilst the increase in NO bioactivity dissipates within weeks of training cessation, studies also indicate that if exercise is maintained, the short-term functional adaptation is succeeded by NO-dependent structural changes, leading to arterial remodelling and structural normalization of shear. Given the strong prognostic links between vascular structure, function and cardiovascular events, the implications of these findings are obvious, yet many unanswered questions remain, not only concerning the mechanisms responsible for NO bioactivity, the nature of the cellular effect and relevance of other autacoids, but also such practical questions as the optimal intensity, modality and volume of exercise training required in different populations.

945 citations