Marek Naruszewicz

Stabilisation of atherosclerotic plaques position paper of the european society of cardiology (ESC) working group on atherosclerosis and vascular biology

Plaque rupture and subsequent thrombotic occlusion of the coronary artery account for as many as three quarters of myocardial infarctions. The concept of plaque stabilisation emerged about 20 years ago to explain the discrepancy between the reduction of cardiovascular events in patients receiving lipid lowering therapy and the small decrease seen in angiographic evaluation of atherosclerosis. Since then, the concept of a vulnerable plaque has received a lot of attention in basic and clinical research leading to a better understanding of the pathophysiology of the vulnerable plaque and acute coronary syndromes. From pathological and clinical observations, plaques that have recently ruptured have thin fibrous caps, large lipid cores, exhibit outward remodelling and invasion by vasa vasorum. Ruptured plaques are also focally inflamed and this may be a common denominator of the other pathological features. Plaques with similar characteristics, but which have not yet ruptured, are believed to be vulnerable to rupture. Experimental studies strongly support the validity of anti-inflammatory approaches to promote plaque stability. Unfortunately, reliable non-invasive methods for imaging and detection of such plaques are not yet readily available. There is a strong biological basis and supportive clinical evidence that low-density lipoprotein lowering with statins is useful for the stabilisation of vulnerable plaques. There is also some clinical evidence for the usefulness of antiplatelet agents, beta blockers and renin-angiotensin-aldosterone system inhibitors for plaque stabilisation. Determining the causes of plaque rupture and designing diagnostics and interventions to prevent them are urgent priorities for current basic and clinical research in cardiovascular area.

The effect of thermally oxidized soya bean oil on metabolism of chylomicrons. Increased uptake and degradation of oxidized chylomicrons in cultured mouse macrophages

Oral administration of thermally oxidized soya bean oil (TO) increased the level of lipid peroxides in human plasma, mainly in chylomicrons. No changes were observed after fresh oil (FO) intake. Human chylomicrons obtained after TO ingestion were rich in lipid peroxides and degraded more rapidly by cultured mouse macrophages than chylomicrons after FO. The uptake of TO chylomicrons by macrophages occurred via a saturable process and was partially inhibited by beta-very low density lipoprotein as well as by acetyl-low density lipoprotein and fucoidin. A 48-h incubation of macrophages with TO chylomicrons caused a 10-fold higher accumulation of cholesterol ester mass in the cells than the incubation with FO chylomicrons. These studies suggest that chylomicrons containing lipid peroxides may be taken up by mouse macrophages by mediation of beta-VLDL receptor as well as by acetyl-LDL receptor, and show a potential pathway by which chylomicrons obtained after ingestion of heated oil could contribute to accumulation of cholesterol esters in macrophages.

Oleuropein and oleacein may restore biological functions of endothelial progenitor cells impaired by angiotensin II via activation of Nrf2/heme oxygenase-1 pathway

Endothelial progenitor cells (EPCs) are responsible for neovascularization of ischaemic tissue and may participate in re-endothelization of an injured arterial wall. There is evidence that angiotensin II, by an increase of gp91phox expression and induction of ROS generation, accelerates cell senescence and impairs functions of EPCs. Oleacein is a main phenolic compound from olive oil, whereas oleuropein is present in olive leaves. Both compounds possess antioxidative, hypotensive and anti-inflammatory properties and show beneficial activity on the cardiovascular system. In this study, we examined whether oleoeuropein and oleacein could protect EPCs against impairment of their functions due to angiotensin-induced cell senescence. CD31(+)/VEGFR-2(+) cells were isolated from young healthy volunteers blood samples and cultured on fibronectin-coated plates with angiotensin (1.0μM) in presence or absence of increasing concentrations (from 1.0 to 10.0 μM) of oleoeuropein or oleacein. As compared to angiotensin II-treated cells, EPCs exposed to oleacein or oleuropein prior to angiotensin II showed a significant increase of proliferation and telomerase activity, and a decrease in the percentage of senescent cells and intracellular ROS formation. Oleacein and oleuropein restored migration, adhesion and tube formation of EPCs diminished by angiotensin II in a concentration-dependent manner. This effect was related to NF-E2-related factor 2 (Nrf2) transcription factor activation and the increase of heme oxygenase-1 (HO-1) expression.

Extracts from Epilobium sp. Herbs, Their Components and Gut Microbiota Metabolites of Epilobium Ellagitannins, Urolithins, Inhibit Hormone-Dependent Prostate Cancer Cells-(LNCaP) Proliferation and PSA Secretion

Extracts from Epilobium sp. herbs have been traditionally used in the treatment of prostate‐associated ailments. Our studies demonstrated that the extracts from Epilobium angustifolium, Epilobium parviflorum and Epilobium hirsutum herbs are potent prostate cancer cells (LNCaP) proliferation inhibitors with IC50 values around 35 µg/ml. The tested extracts reduced prostate specific antigen (PSA) secretion (from 325.6 ± 25.3 ng/ml to ~90 ng/ml) and inhibited arginase activity (from 65.2 ± 1.1 mUnits of urea/mg of protein to ~40 mUnits of urea/mg protein). Selected constituents of extracts (oenothein B, quercetin‐3‐O‐glucuronide, myricetin‐3‐O‐rhamnoside) were proven to be active in relation to LNCaP cells. However, oenothein B was the strongest inhibitor of cells proliferation (IC50 = 7.8 ± 0.8 μM), PSA secretion (IC50 = 21.9 ± 3.2 μM) and arginase activity (IC50 = 19.2 ± 2.0 μM). Additionally, ellagitannins from E. hirustum extract were proven to be transformed by human gut microbiota into urolithins. Urolithin C showed the strongest activity in the inhibition of cell proliferation (IC50 = 35.2 ± 3.7 μM), PSA secretion (reduced PSA secretion to the level of 100.7 ± 31.0 ng/ml) and arginase activity (reduced to the level of 27.9 ± 3.3 mUnits of urea/mg of protein). Results of the work offer an explanation of the activity of Epilobium extracts and support the use of Epilobium preparations in the treatment of prostate diseases. Copyright

Novel Biological Properties of Oenothera paradoxa Defatted Seed Extracts: Effects on Metallopeptidase Activity

In this study, for the first time, we used the in vitro metallopeptidase model for the identification of a potential novel activity of defatted evening primrose seed extracts. Prepared extracts of different polarity (aqueous, 60% ethanolic, isopropanolic, and 30% isopropanolic) at concentrations of 1.5-100 microg/mL exhibited a significant and dose dependent inhibition of three tested enzymes. The 50% inhibition of enzymes activity showed that aminopeptidase N (APN) was the enzyme affected to the greatest extent with IC50 at the level of 2.8 microg/mL and 2.9 microg/mL for aqueous and 30% isopropanolic extracts, respectively. The activity of neutral endopeptidase (NEP) was quite strongly inhibited by the extracts as well. The HPLC-DAD analysis and bioguided fractionation led to the identification of four active compounds: (-)-epicatechin gallate, proanthocyanidin B3, oenothein B, and penta-O-galloyl-beta-D-glucose (PGG). Oenothein B has been shown previously to inhibit metallopeptidases. The three other compounds are known to inhibit angiotensin-converting enzyme (ACE), but they have not been previously reported to inhibit the NEP and APN activity. PGG and procyanidins with different degrees of polymerization, as the dominating compounds in O. paradoxa seeds, seemed to play a role in the crude extract activity.

Oenothera paradoxa defatted seeds extract and its bioactive component penta-O-galloyl-β-D-glucose decreased production of reactive oxygen species and inhibited release of leukotriene B4, interleukin-8, elastase, and myeloperoxidase in human neutrophils.

In this study, we analyzed ex vivo the effect of an aqueous extract of Oenothera paradoxa defatted seeds on the formation of neutrophil-derived oxidants. For defining active compounds, we also tested lypophilic extract constituents such as gallic acid, (+)-catechin, ellagic acid, and penta-O-galloyl-β-D-glucose and a hydrophilic fraction containing polymeric procyanidins. The anti-inflammatory potential of the extract and compounds was tested by determining the release from activated neutrophils of elastase, myeloperoxidase, interleukin-8 (IL-8), and leukotriene B4 (LTB4), which are considered relevant for the pathogenesis of cardiovascular diseases. The extract of O. paradoxa defatted seeds displays potent antioxidant effects against both 4β-phorbol-12β-myristate-α13-acetate- and formyl-met-leu-phenylalanine-induced reactive oxygen species production in neutrophils with IC50 values around 0.2 μg/mL. All types of polyphenolics present in the extract contributed to the extract antioxidant activity. According to their IC50 values, penta-O-galloyl-β-D-glucose was the more potent constituent of the extract. In cell-free assays, we demonstrated that this effect is partially due to the scavenging of O2- and H2O2 oxygen species. The extract and especially penta-O-galloyl-β-D-glucose significantly inhibit elastase, myeloperoxidase IL-8, and LTB4 release with an IC50 for penta-O-galloyl-β-D-glucose of 17±1, 15±1, 6.5±2.5, and around 20 μM, respectively. The inhibition of penta-O-galloyl-β-D-glucose on reactive oxygen species and especially on O2- production, myeloperoxidase, and chemoattractant release may reduce the interaction of polymorphonuclear leukocyte with the vascular endothelium and by that potentially diminish the risk of progression of atherosclerosis development.

Epidemiology and prevention of arterial hypertension in Poland

The authors review the present situation in epidemiology and prevention of arterial hypertension in Poland. In 2002, the NATPOL PLUS survey on representative sample of adults (n=3051, age range 18–93) was conducted. Prevalence of hypertension, diagnosed on basis of three separate visits, was 29%, awareness 67% and efficacy of treatment 12.5%. Thus, in Poland, one-third of 8.6 million hypertensives are unaware of their disease. A comparison with data from other countries should be careful due to the different methods (age range, number of readings and visits) used in the studies. The data, in concert with a decrease in awareness of ones own blood pressure (from 71% in 1994 to 59% in 2002), called for urgent preventive measures. Two large interventions were implemented under the National Programme POLKARD in 2003: the Polish 400 Cities Project aimed to increase detection and knowledge of hypertension and other risk factors among small-town and village communities, and the educational project, A Chance for the Young Heart targeted at children aged 11–14 years and using traditional teaching methods and an interactive Internet website. Also, an educational and marketing programme targeted at public opinion leaders and decision makers (trade unions, local governments, healthcare financing authorities, print media and radio, the Polish Parliament) started in 1999 and is still in process.

Extracts from Epilobium sp. herbs induce apoptosis in human hormone‐dependent prostate cancer cells by activating the mitochondrial pathway

The aim of this work was to determine the effect of standardized aqueous extracts from Epilobium angustifolium L., E. parviflorum Schreb. and E. hirsutum L. herbs on the apoptosis of hormone‐dependent prostate cancer cells (LNCaP).

The influence of clofibrate on lipid and protein components of very low density lipoproteins in type IV hyperlipoproteinaemia

After 30 days of clofibrate administration to 11 patients with type IV hyperlipoproteinemia, a significant fall was observed in serum triglyceride and cholesterol levels. In the VLDL fraction the concentrations of triglycerides, cholesterol and apo B were significantly decreased. The apo CII/apo CIII ratio was raised. Cholesterol concentration changes in LDL and HDL fractions were not significant.

Inhibition of human neutrophils NEP activity, CD11b/CD18 expression and elastase release by 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde, oleacein

Polyphenols, such as oleacein (3,4-DHPEA-EDA; 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde), are believed to play a role in the prevention of cardiovascular diseases. Due to an increase of neutrophil mediators in acute myocardial infarction the aim of this study was to establish the effect of oleacein on neutral endopeptidase (NEP) activity and other functions of human neutrophils, such as elastase, MMP-9 and IL-8 production. The effect on CD62L and CD11b/CD18 expression on neutrophils was also determined. Oleacein with a concentration of 100 μM inhibited NEP activity, elastase, MMP-9 and IL-8 release from neutrophils by 77.7 ± 2.7%, 21.3 ± 7.8%, 22.7 ± 4.2% and 25.2 ± 5.6%, respectively. Oleacein with a concentration of 50 μM suppressed CD11b/CD18 expression by 63.6 ± 3.1% and to a lesser extent, increased CD62L expression by 27.3 ± 8.3% on the surface of neutrophils, in comparison with stimulated cells. Oleacein by inhibiting NEP activity, adhesion molecules expression and elastase release might play a role in the protective effects of olive oil against endothelial injuries.