J. Nanobachvili

Simvastatin decreases free radicals formation in the human abdominal aortic aneurysm wall via NF-κB.

OBJECTIVES Statins have been reported to suppress the progression of abdominal aortic aneurysm (AAA). However, the effects of statins on inflammatory processes and free radicals generation are poorly understood. METHODS Wall samples from 51 patients (simvastatin patients, n = 34; non-statin patients, n = 17; matched by sex, age and aneurysm size) subjected to elective open AAA repair were analysed. We examined the effects of simvastatin on lipid peroxidation (4-hydroxy-trans-2-nonenal (4-HNE)), hydrogen peroxide (H(2)O(2)), tumour necrosis factor alpha (TNF-α) concentration, superoxide dismutase (SOD) and catalase (CAT) activity as well as nuclear factor kappa B (NF-κB) pathway activation in human AAA wall samples. RESULTS Treatment with simvastatin resulted in a decrease in 4-HNE and TNF-α concentration (median 4.18 μg/mg protein vs. 4.75, p = 0.012; median 10.33 pg/ml vs. 11.81, p = 0.026, respectively). CAT activity was higher in the simvastatin group (median 3.98 U ml vs. 3.19, p = 0.023). NF-κB expression was lower (p = 0.018) in the simvastatin group. However, simvastatin had little effect on H(2)O(2) concentration (p = 0.832) and SOD activity (p = 0.401). CONCLUSION Simvastatin inhibits free radicals and TNF-α generation and improves antioxidant capacity of human AAA wall tissue, possibly through the suppression of NF-κB activity. This may be one possible explanation how statins can inhibit AAA oxidative stress.

Decreased Tissue Levels of Cyclophilin A, a Cyclosporine A Target and Phospho-ERK1/2 in Simvastatin Patients with Abdominal Aortic Aneurysm

BACKGROUND Cyclophilin A (CyPA), a cyclosporine A-binding protein, influences abdominal aortic aneurysm (AAA) formation and the ERK1/2 signalling pathway in animal and in vitro studies. Statins decrease CyPA in smooth muscle cells although their influence on CyPA in human AAA is unknown. MATERIAL AND METHODS The study was performed on AAA wall-tissue samples obtained from 30 simvastatin-treated and 15 non-statin patients (2:1 case to control). The patients were matched by age, sex and AAA diameter. We investigated the gene expression of CyPA, its receptor extracellular matrix metalloproteinase inducer (EMMPRIN) by real-time RT-PCR. CyPA and EMMPRIN protein level and phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) were measured by Western blot. RESULTS The AAA wall tissue from simvastatin-treated patients had significantly lower CyPA gene expression and protein levels (P = 0.0018, P = 0.0083, respectively). Furthermore, phosphorylation of ERK1 and ERK2 was markedly suppressed in the simvastatin group (P = 0.0002, P = 0.0027, respectively). However, simvastatin did not influence EMMPRIN gene and protein expression. CONCLUSION Simvastatin-treated patients with AAA exert lower CyPA messenger RNA (mRNA), as well as CyPA intracellular protein levels and a decreased amount of phospho-ERK1/2. Thus, the interference with signalling pathways leading to CyPA formation and ERK1/2 activation reveals a new anti-inflammatory role of statins in AAA.

NGAL and MMP-9/NGAL as biomarkers of plaque vulnerability and targets of statins in patients with carotid atherosclerosis

Abstract Background: Neutrophil gelatinase associated lipocalin (NGAL) is expressed in atherosclerotic lesions and was recently implicated in the pathogenesis of cardiovascular pathologies. Statins are known to exert stabilizing effects on atherosclerotic plaque. The aims of our study were (1) to investigate the association of serum NGAL and metalloproteinase (MMP)-9/NGAL complex with the vulnerability of the atherosclerotic plaque, and (2) to reveal the effects of statin treatment on circulating NGAL and MMP-9/NGAL levels in patients with carotid artery stenosis. Methods: We examined the levels of NGAL and MMP-9/NGAL in blood samples from 136 patients with carotid artery stenosis by specific enzyme-linked immunosorbent assays. Results: Patients with vulnerable plaques, as determined by ultrasound (plaques with decreased echogenicity) and histological analysis (type VI according to the classification of American Heart Association [AHA]), displayed the highest levels of NGAL (both p<0.0001) and MMP-9/NGAL complex (p=0.0004 and p=0.004, respectively). Moreover, patients with symptomatic carotid atherosclerosis had significantly higher NGAL levels compared to asymptomatic patients (p=0.0007). The statin-treated group (n=108) demonstrated lower NGAL (73.9 vs. 128.0 μg/L, p<0.0001) and MMP-9/NGAL (28.9 vs. 40.6 μg/L, p=0.046) as compared to the non-statin group (n=28). Furthermore, in multivariate regression analysis NGAL, but not MMP-9/NGAL levels, were independently associated with symptomatic carotid artery stenosis. In addition, statin treatment was independently associated with lower NGAL levels. Conclusions: Circulating NGAL and MMP-9/NGAL are associated with plaque vulnerability in patients with carotid artery stenosis. Statin treatment could contribute to plaque stabilization by reducing circulating NGAL and MMP-9/NGAL levels.

Analysis of host Toll-like receptor 3 and RIG-I-like receptor gene expression in patients with abdominal aortic aneurysm

Objective: Abdominal aortic aneurysm (AAA) is a vascular disease relatively common in the elderly population. Although some events that contribute to the development and progression of AAA are known, there are limited data examining the association of Toll‐like receptor 3 (TLR3) and RIG‐I‐like receptor expression with the pathogenesis of AAAs. In this study, we investigated the gene and protein expression of TLR3 and RIG‐I‐like receptors (RIG‐I and MDA5) in aortic wall and blood of AAA patients and examined the relationship between their expression and immune response. Methods: Total RNA was extracted from aortic wall tissues and blood samples collected from 20 patients with AAA and blood samples of 17 healthy volunteers without aortic aneurysm. To evaluate the DDX58 (RIG‐I), IFIH1 (MDA5), and TLR3 gene expression level, quantitative real‐time polymerase chain reaction was used. Extracellular cytokine and pattern recognition receptor levels were quantified by enzyme‐linked immunosorbent assays. Results: TLR3, RIG‐I, and MDA5 were constitutively expressed in both aortic tissues and blood samples from AAA patients and healthy volunteers. In patients with AAA, higher TLR3 expression in aortic tissues than in blood was found (P = .004). The DDX58 messenger RNA expression was higher in blood of patients with AAA compared with healthy subjects (P = .021). A significantly higher level of plasma interleukin 4 was noticed in patients with AAA than in healthy individuals (P = .008). Conclusions: This study suggests that RIG‐I and TLR3 seem to be important factors in the pathogenesis of AAA. Clinical Relevance: Abdominal aortic aneurysm is a vascular disease relatively common in the elderly population. This study shows that Toll‐like receptor 3 and RIG‐I‐like receptors may contribute to the development and progression of abdominal aortic aneurysm.

Repair of abdominal aortic aneurysms : The benefits of offering both endovascular and open surgical techniques

Two treatment options are available for abdominal aortic aneurysms (AAAs): open surgical technique with graft replacement and endovascular aortic aneurysm repair (EVAR) as a minimally invasive procedure. The intention of this review is to highlight the advantages of both procedures and to demonstrate that offering both procedures is beneficial for the patient when he or she makes the important decision regarding which treatment to select. A comparative evaluation of both treatment options is offered as well as a short description of the risk of rupture and its consequences. The authors discuss the latest literature as well as their own experiences. An innovative statistical approach-the propensity score-based Cox model-is presented to evaluate the 2 treatment options. The benefits of offering both EVAR and open surgery permit optimal management of AAA for the individual patient and tailor the treatment to his or her organ dysfunctions and impaired physical status. In addition, EVAR offers a treatment option for otherwise incurable high-risk patients.

Gefäßchirurgische Behandlung der Krampfadern

ZusammenfassungGrundlagen: Krampfadern sind eine weit verbreitete Erkrankung, die Beschwerden und Komplikationen verursachen kann. Deshalb sind adäquate diagnostische und therapeutische Verfahren wichtig. In der letzten Dekade haben sich die nicht invasiven diagnostischen Methoden rapide entwickelt. Mittels Duplex-Ultraschalluntersuchung kann man die Morphologie des Venensystems, die Lokalisation der insuffizienten Klappen und Thrombosen sowohl in oberflächlichen als auch in tiefen Venen darstellen. Heute gibt es im Wesentlichen zwei Möglichkeiten, eine medizinisch bedeutende, krankhafte Varikose operativ zu behandeln: „radikale Varizenoperation = 4-Schritt-Operation“ (Crossektomie, Stripping, Ligatur der Vv. Perforantes, Phlebektomie) und die hohe Ligatur der Vena saphena magna (ohne Stripping). Methodik: Der aktuelle Stand der chirurgischen Behandlung variköser Venen wurde untersucht. Die Langzeit-Ergebnisse der „radikalen Varizenoperation“ wurden mit denen der „hohen Ligatur“ verglichen. Ergebnisse: Die publizierten Ergebnisse bestätigen die Überlegenheit der Radikaloperation gegenüber der „hohen Ligatur“. Die exakte Identifikation und Ligatur aller Seitenäste an der sapheno-femoralen Mündung und die Ligatur der relevanten Vv. Perforantes sind wichtige Schritte der „radikalen Varizenoperation“, um einer Rezidivvarikose vorzubeugen. Schlußfolgerungen: Die Radikaloperation ermöglicht eine effektivere Kontrolle des Reflux, erzielt ein besseres Resultat, hat langfristig gesehen eine geringere Rezidivrate und sollte als optimale Technik der chirurgischen Behandlung einer Varikose gelten.SummaryBackground: Varicose disease is widely prevalent, causing discomfort and disability of patients. Therefore, adequate diagnostic and treatment modalities are important.In the last decade, non-invasive diagnostic methods developed rapidly. Duplex-ultrasonographic examination shows the morphology of the venous system, distribution of insufficient valves and reveals thrombosis in the both superficial and deep veins. Today there are two different methods of surgical treatment of varicose veins: radical operation (crossectomy, stripping, ligature of the insufficient perforating veins, phlebectomy) and high ligation of the saphenous vein without stripping. Methods: The current status of surgery for varicose veins is reviewed. “Radical operation” is compared to “high ligature” in terms of long-term outcome. Results: The published results are convincing evidence of the superiority of radical operation over high ligature. Accurate identification and ligation of all tributaries at saphenofemoral junction, ligation of relevant perforating veins are important steps of the radical operation in preventing recurrent varicose. Conclusions: Radical surgery of varicose veins provides good results of treatment, prevents better the recurrence of the disease and should be considered the optimal method of treatment.

Editorial: Diagnose und Therapie von Varizen

Apparative Diagnostik der Varikose Die Diagnostik sollte sowohl eine sorgf~ltige ktinische Untersuchung als auch funktionelle und bildgebende Veffahren beinhalten. Die alleinige klinische peinlich genaue Untersuchung ist aber nicht als ausreichend anzusehen. Duplexsonographie und aszendierende Pre6phlebographie sind akzeptierte bildgebende Routinemethoden for die prfioperative Varizendiagnostik. Es sollte abet die Ultraschalluntersuehung als nichtinvasive Methode bevorzugt werden. Zwei Voraussetzungen mtissen allerdings gegeben sein: ein FarbDuplex-Ultraschall-Ger~it und ein erfahrener Untersucher. Die Ultrasonographie erm6glicht sowohl morphologische als auch funktionelle Aussagen yon diagnostischer Relevanz fiir die exakte Therapieplanung. Nur Patienten mit unklaren UltraschallErgebnissen oder Rezidivvarikosen sollten einer ergfinzenden Phlebographie unterzogen werden (1). Die Ultrasonographie erm6glicht prfioperativ eine direkte Markierung der Perforansvehen auf der Haut, was sich for den Chirurgen als unverzichtbar erweist. Ein gewisser Vortei.! des Phlebogramms gegen~iber der Duplexsonographie ist die Ubersichtlichkeit des Gesamtbildes und eine bessere Dokumentationsm6glichkeit.