Biomedical subjects

J Jawien

Publications and source records attributed to J Jawien.

5 recordsLinked to original sources

PubMed2006

Hypercholesterolemia does not alter endothelial function in spontaneously hypertensive rats.

In humans, hypercholesterolemia and hypertension are associated with endothelial dysfunction. Here, we assess whether hypercholesterolemia induces endothelial dysfunction in rats with pre-existing hypertension. Spontaneously hypertensive rats (SHR) and normotensive controls (WKY) were fed with a high-cholesterol diet for 12 weeks, and endothelial function was assessed in isolated thoracic aortic rings. In SHR and WKY rats, the hypercholesterolemic diet resulted in the elevation of total cholesterol and low-density lipoprotein levels by approximately 2.5- and 4.5-fold, respectively. However, in aorta, the basal nitric oxide (NO) production--as assessed by the magnitude of L-NG-nitroarginine methyl ester-induced vasoconstriction as well as the NO-dependent relaxation induced by acetylcholine or histamine--were not diminished either in SHR or in WKY rats fed with the hypercholesterolemic diet. Interestingly, prostacyclin (PGI2) production in aortic rings from SHR rats was higher than in the aorta from WKY rats. However, the hypercholesterolemic diet had no further effects on PGI2 production in the aorta either of SHR or WKY rats. The monocyte chemoattractant protein 1 level in plasma was slightly elevated in SHR and WKY rats fed with the hypercholesterolemic diet compared with their normocholesterolemic counterparts. In summary, even in the presence of pre-existing hypertension, hypercholesterolemia fails to modify NO-dependent and PGI2-dependent endothelial function in SHR rats; it also does not induce a robust inflammatory response. Both are prerequisites for the development of atherosclerosis.

Animals↗

PubMed2006

Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice.

BACKGROUND: Recent reports point to an important role of leukotrienes in atherogenesis. Leukotrienes are produced by 5-lipoxygenase co-operating with five lipoxygenase activating protein (FLAP). We hypothesized that MK-886, an inhibitor of FLAP, could attenuate the development of atherosclerosis in the atherogenic apolipoprotein E/low density lipoprotein receptor (apoE/LDLR) double knockout (DKO) mouse model. MATERIALS AND METHODS: Female apoE/LDLR-DKO mice at the age of 8 weeks were put on Western diet. The experimental group (n = 10) received the same diet as the control group (n = 10), but mixed with MK-886 (Merck, Rahway, NJ) at a dose of 4 microg per 100 mg of body-weight per day. At age 6 months the mice were sacrificed under anaesthesia. RESULTS: Measured by the en face method, the percentage of area occupied by lesions in aortas in the control group was 25.15 +/- 2.9%, whereas in the MK-886-treated group it was 11.16 +/- 0.7% (P < 0.05). Lesion area measured by cross-section of aortic roots was 455,494 +/- 29,564 microm(2) in the control group versus 263,042 +/- 20,736 microm(2) in the MK-886-treated group (P < 0.05). The MK-886 did not change the plasma cholesterol lipoprotein profile as compared with the control mice. Finally, we show that MK-886 may increase plaque stability by decreasing the macrophage content as well as increasing the collagen and smooth-muscle cell content. CONCLUSIONS: Our results show for the first time that inhibition of FLAP by MK-886 reduces development of atherosclerosis in gene-targeted apoE/LDLR-DKO mice.

5-Lipoxygenase-Activating Proteins↗

PubMed2005

Endothelial action of thienopyridines and thienopyrimidinones in the isolated guinea pig heart.

Antiplatelet thienopyridines (ticlopidine, clopidogrel) and their thienopyrimidinone congeners, induce prostacyclin-dependent thrombolysis in vivo. Here we tested whether thienopyridines (ticlopidine, clopidogrel, and its enantiomer without antiplatelet properties) and structurally related thienopyrimidinones release NO from coronary endothelium in the isolated guinea pig heart, perfused according to Langendorff technique. The involvement of endothelium-derived NO in coronary vasodilation induced by these agents was assessed by effect of L-N(G)-nitro-arginine methyl ester (L-NAME). In addition, effect of thienopyridines or thienopyrimidinones on nitrite accumulation in cultured endothelium was assayed. Tienopyridines (10-100 micromol L(-1)) and thienopyrimidinones (10-30 micromol L(-1)) produced concentration-dependent increase in coronary flow comparable to that induced by acetylcholine (0.1 micromol L(-1)) or bradykinin (3 nmol L(-1)) which was inhibited by L-NAME (by 50-70%) but not by indomethacin. Furthermore, thienopyridines and thienopyrimidinones caused NO release from cultured endothelial cells. In conclusion, both thienopyridines independently from their antiplatelet action and their thienopyrimidinone congeners that are devoid of antiplatelet action stimulate coronary endothelium to release NO. Endothelial action of these compounds merits further investigation.

Animals↗

PubMed2005

Superoxide dismutase activity and expression in human venous and arterial bypass graft vessels.

UNLABELLED: Venous bypass grafts are more prone to accelerated atherosclerosis than arterial grafts, which is partly related to increased oxidative stress and diminished nitric oxide bioavailability. In veins superoxide production is dependent primarily on nox2 NAD(P)H oxidase expression, while in arteries nox4 appears to play an important role. This may in part explain differences in susceptibility to graft failure. Net levels of oxidative stress are however determined in parallel by the production as well as by degradation of free radicals (eg. by superoxide dismutases, catalases, thioredoxins etc). The differences in superoxide dismutase (SOD) expression and activity in human bypass conduit vessels remain unclear. Accordingly, we aimed to compare SOD activity and protein levels as well as its functional effects on superoxide production in segments of human internal mammary arteries (IMA) and saphenous veins (HSV) from patients undergoing bypass graft surgery (n=24). SOD activity was assessed by inhibition of pyrogallol autoxidation, Cu-Zn SOD and Mn SOD protein levels were studied by immunoblotting. Basal superoxide release was detected by lucigenin (5 microM) enhanced chemiluminescence. Total SOD activity did not differ significantly between HSV and IMA. Similarly, no difference was observed in SOD activity in the presence of KCN (Mn-SOD). Human bypass conduit vessels show amounts of Cu-Zn SOD or Mn-SOD protein levels. In both HSV and IMA segments superoxide production was more than doubled in the presence of SOD inhibitor-DETC. CONCLUSIONS: These studies suggest that the differences in oxidative stress between human arteries and veins are unlikely to be caused by SOD activity. However SOD plays and important role in amelioration of oxidative stress in both types of vessels.

Coronary Artery Bypass↗

PubMed2002

A new insight into aspirin-induced asthma.

In about 10% of adult patients with asthma, aspirin and other nonsteroidal anti-inflammatory drugs precipitate attacks of dyspnoea. Accumulated evidence shows that these reactions are due to the interference of aspirin-like drugs with arachidonic acid metabolism in the lungs of the sensitive patients: inhibition of cyclooxygenase is accompanied by overproduction of cysteinyl leukotrienes. The mechanisms of these reactions and the characteristic course of aspirin-induced asthma and its management are discussed.

Adult↗