The infiltration of red blood cells into atheromatous plaques is implicated in atherogenesis. Inside the lesion, hemoglobin (Hb) is oxidized to ferri- and ferrylHb which exhibit prooxidant and proinflammatory activities. Cystathione gamma-lyase- (CSE-) derived H2S has been suggested to possess various antiatherogenic actions. Expression of CSE was upregulated predominantly in macrophages, foam cells, and myofibroblasts of human atherosclerotic lesions derived from carotid artery specimens of patients. A similar pattern was observed in aortic lesions of apolipoprotein E-deficient mice on high-fat diet. We identified several triggers for inducing CSE expression in macrophages and vascular smooth muscle cells including heme, ferrylHb, plaque lipids, oxidized low-density lipoprotein, tumor necrosis factor-α, and interleukin-1β. In the interplay between hemoglobin and atheroma lipids, H2S significantly mitigated oxidation of Hb preventing the formation of ferrylHb derivatives, therefore providing a novel function as a heme-redox-intermediate-scavenging antioxidant. By inhibiting Hb-lipid interactions, sulfide lowered oxidized Hb-mediated induction of adhesion molecules in endothelium and disruption of endothelial integrity. Exogenous H2S inhibited heme and Hb-mediated lipid oxidation of human atheroma-derived lipid and human complicated lesion. Our study suggests that the CSE/H2S system represents an atheroprotective pathway for removing or limiting the formation of oxidized Hb and lipid derivatives in the atherosclerotic plaque.

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Technetium-99m sestamibi was used for functional investigation of the muscle perfusion of lower extremities in 35 patients with peripheral vascular disease. The aim was to test what useful information could be obtained by additional imaging of the legs in patients referred for risk stratification with dipyridamole myocardial scanning. Posterior images were acquired over the thighs and calves after postocclusive reactive hyperaemia and at rest. Inter- and intraextremity ratios and differences between the stress and rest data were used for the assessment of abnormal circulation. Arteriography was performed in every case, and surgical procedures or transluminal angioplasty in 31 patients. To estimate diagnostic accuracy, the results of 99mTc-sestamibi scintigraphy were compared with those of angiography and the functional consequences of revascularization procedures. The sensitivity and specificity of 99mTc-sestamibi scintigraphy were 55% and 25%, respectively, with an overall accuracy of 50%. Apparently methodological error was not responsible for these poor results. Instead, a paradoxically high uptake of the radiopharmaceutical in muscles supplied by significantly stenosed vessels was identified as the main source of both false-negative and false-positive results. The phenomenon resembles the findings of a previous study involving delayed administration of thallium-201 after exercise. In conclusion, 99mTc-sestamibi scintigraphy has not proved sufficiently reliable to help in the management strategy for patients with peripheral vascular disease.

Atherosclerosis is a systemic disease affecting the coronary, carotid, intracerebral, renal and peripherial arteries. The early morphological and functional impairments could be detected in the second or third decades of life and their progression depend on the number and severity of risk factors and individual susceptility. Although the vascular risk factors (smoking, overweight, age, unhealthy diet, lack of physical exercise, hypertension, diabetes mellitus, chronic kidney disease and dyslipidemia) are the same and common in the different vascular diseases, the present clinical routine artificially classifies the diagnosis and therapy of different vascular diseases into different subfields of medicine with the negative impact of possible polypragmasia. Recently, worldwide health surveys (e.g. REACH registry) have proven the usefulness of a holistic approach in the diagnosis and therapy of multiorgan-affected vascular patients. This review summarizes the multidisciplinary advances and future perspective of vascular diseases. Orv. Hetil., 2012, 153, 483–498.

Dynamic imaging of the inflow of technetium-99m hexamethylpropylene amine oxime (HMPAO) to the brain has been proved to allow estimation of the hemispherical cerebral blood flow (CBF) using the Patlak plot. In this study, we compared the hemispherical CBF (in ml/min/100 g) of different patient groups. A total of 25 patients (comprising 13 with migraine and 12 scheduled for endarterectomy owing to angiographically confirmed severe stenosis of the internal carotid artery on at least one side) underwent baseline and acetazolamide 99mTc-HMPAO brain perfusion studies. In addition, acetazolamide 99mTc-HMPAO studies were performed in 12 healthy subjects (no baseline study was performed for ethical reasons.) Dynamic studies were acquired by means of a dual-detector gamma camera with a large field of view (HELIX, Elscint). Special difference images were created to make definition of the aortic arch and hemispherical brain regions easier and more reproducible. A semi-automatic method was developed to determine the transit time from the aorta to the brain, making the generation of the Patlak plot even more robust. The baseline CBF values did not significantly depend on the disease (P>0.1), whereas the CBF values obtained after acetazolamide provocation did do so (ANOVA, P<0.001). Patients suffering from migraine showed a significant increase in global CBF values after acetazolamide provocation (paired t test, P<0.05), but we could not find any effect of the provocation in patients awaiting carotid endarterectomy, indicating a lack of cerebrovascular reserve capacity. Comparison of the results of the acetazolamide study in patients and the control group revealed the CBF values to be significantly lower in patients with carotid stenosis (two-sample t-test, P<0.001), but not in those with migraine (P>0.1). In summary, using quantitative analysis of 99mTc-HMPAO brain studies we could objectively compare the CBF of patients suffering from different diseases. Especially the CBF values obtained after acetazolamide provocation permitted effective differentiation of disease states. The quantitative results may be of assistance in therapy planning, e.g. in selection of the correct operative technique.