Glycosylation enhances oxygen radical-induced modifications and decreases acetylhydrolase activity of human low density lipoprotein

Background. Posttranslational nonenzymatic glycosylation of native low-density lipoprotein (n-LDL) occurs bothin vitro andin vivo in diabetic patients. Glycosylated LDL (glc-LDL) behave similarly to oxidized LDL in some respects. In fact, unlike n-LDL, uptake of glc-LDL can occur in part by the scavenger receptor(s), as also demonstrated for oxidized LDL. The enzyme acetylhydrolase, carried by LDL, catabolizes platelet activating factor (PAF). This enzymatic activity is inhibited in oxidized LDL. However, it is unknown whether glc-LDL have reduced acetylhydrolase activity.Objectives. The first aim of the study was to investigate whether glc-LDL were more susceptible than n-LDL to oxidative modification, and which different oxygen radical species were involved in the phenomenon. Moreover, in order to investigate whether glycosylation may affect acetylhydrolase, we also measured this enzymatic activity in both n- and glc-LDL.Methods. In vitro glc-LDL and n-LDL were exposed to the oxidants xanthine/xanthine oxidase (X/XO; 2 mM and 100 mU/ml, respectively), or CuSO₄ (10 M) for 18 hs at 37°C. Parallel experiments were done in the presence of the superoxide radical scavenger superoxide dismutase (SOD; 330 U/ml), the hydrogen peroxide scavenger catalase (1000 U/ml), or the hydroxyl radical scavenger dimethylthiourea (10 mM) or dimethylsulfoxide (1 mM). Standards of PAF and lyso-PAF were visualized with iodine vapors after separation by thin layer chromatography. The distribution of label was determined by an imaging scanner. Labeled products were then isolated from the chromatography plate, and the amount of³H-lyso-PAF formed was determined by liquid scintillation counting.Results. Glc-LDL were more susceptible than n-LDL to lipid peroxidation (n-LDL 22.9±3.4 vs 34.8±4.2^* nmoles/MDA/mg of protein in glc-LDL oxidized by X/XO and n-LDL 28.9±4.2 vs 40.4±4.1^* in glc-LDL oxidized by CuSO₄,^*p<0.05 vs n-LDL). SOD, but not other scavengers, prevented peroxidation, indicating an obligatory role for superoxide radicals. Oxidation of glc-LDL also induced a higher degree of apolipoprotein-B₁₀₀ modifications than n-LDL, with increased electrophoresis mobility and decreased TNBS reactivity. These effects were similarly prevented by SOD. Finally, acetylhydrolase activity was significantly lower in glc-LDL than in n-LDL.Conclusion. Glycosylation increases LDL oxidation due to superoxide radicals, and also reduces acetylhydrolase activity. These phenomenona may contribute to enhance and/or accelerate the progression of atherosclerosis in diabetic patients.Abbreviation LDL low density lipoprotein - n-LDL native LDL - glc-LDL glycosylated LDL - PAF platelet activating factor - X/XO xanthine/xanthine oxidase reaction - SOD superoxide dismutase - DMTU dimethylthiourea - DMSO dimethylsulfoxide - TNBS trinitrobenzenesulfonic acid - MDA malonyldialdehyde - LPO lipid peroxides This study was presented in abstract form at the 42nd Annual Scientific Session of the American College of Cardiology, Anaheim, CA, 14–18 March 1993 (see Ref. 30).     

Additive effects of simulated climate changes,elevated CO2, and nitrogen deposition on grassland diversity

Biodiversity responses to ongoing climate and atmospheric changes will affect both ecosystem processes and the delivery of ecosystem goods and services. Combined effects of co-occurring global changes on diversity, however, are poorly understood. We examined plant diversity responses in a California annual grassland to manipulations of four global environmental changes, singly and in combination: elevated CO2, warming, precipitation, and nitrogen deposition. After 3 years, elevated CO2 and nitrogen deposition each reduced plant diversity, whereas elevated precipitation increased it and warming had no significant effect. Diversity responses to both single and combined global change treatments were driven overwhelmingly by gains and losses of forb species, which make up most of the native plant diversity in California grasslands. Diversity responses across treatments also showed no consistent relationship to net primary production responses, illustrating that the diversity effects of these environmental changes could not be explained simply by changes in productivity. In two- to four-way combinations, simulated global changes did not interact in any of their effects on diversity. Our results show that climate and atmospheric changes can rapidly alter biological diversity, with combined effects that, at least in some settings, are simple, additive combinations of single-factor effects.     

Pattern of left ventricular filling in hypertrophic cardiomyopathy: Assessment by Doppler echocardiography and radionuclide angiography

Aims The left ventricle in hypertrophic cardiomyopathy is anatomicallyand functionally non-uniform. This study was undertaken to verifywhether a heterogeneity in the pattern of diastolic fillingcan be detected along the left ventricular inflow tract in hypertrophiccardiomyopathy. Methods and results Early (E) and late (A) diastolic velocitieswere recorded by Doppler echocardiography at mitral and at mid-ventricularlevel in 16 normal volunteers and 30 patients with hypertrophiccardiomyopathy. Patients with hypertrophic cardiomyopathy alsounderwent radionuclide angiography to assess left ventricularfunction. E wave decreased significantly in normal volunteers(80±15 to 60±14cm.s^–1;P<0·001),but it increased in hypertrophic cardiomyopathy (76±22to 87±28cm.s^–1;P=0·04), whereas the A wavedecreased similarly in both. By multivariate analysis, systolicasynchrony and the ejection fraction of left ventricular lateralwall were directly related to the pattern of early filling progression(r=0·656; F=9·467;P<0·002). Moreover,systolic asynchrony showed a univariate direct correlation withchanges in E velocity (r=0·42;P=0·02). Conclusion Many patients with hypertrophic cardio-myopathy havean acceleration of filling within the left ventricular inflowtract; this phenomenon is directly related to systolic asynchronyand ejection fraction of the left ventricular lateral wall,suggesting increased suction.     

Abdominal Aortic dissections: anatomic and clinical features and therapeutic options

Isolated abdominal aortic dissections are rare events. Their anatomic and clinical features are different from those of atherosclerotic aneurysms. We report 4 cases of isolated abdominal aortic dissection that were successfully treated with surgical or endovascular intervention. The anatomic and clinical features and a review of the literature are also presented.     

Mechanisms and predictors of transient left ventricular dysfunction early after successful percutaneous balloon mitral valvuloplasty.

BACKGROUND: The immediate effects of balloon mitral valvuloplasty (BMV) on left ventricular (LV) function in patients with mitral stenosis are still controversial. The aim of this study was to investigate the mechanisms and potential clinical, echocardiographic and hemodynamic predictors of transient LV dysfunction occurring in patients with mitral stenosis early after successful percutaneous BMV. METHODS: Sixty patients without residual mitral regurgitation were divided into two groups according to the changes in the left atrial (LA) pressure 15 min after successful BMV: 18 patients (group A) did not present with any reduction in LA pressure, and underwent nitroglycerin administration (0.4 mg, sublingually). The remaining 42 patients (group B) presented with a decrease in LA pressure. RESULTS: At baseline, both the mitral valve gradient and area assessed at echocardiography and during cardiac catheterization were similar in groups A and B. Group A patients presented with, however, higher LV early- and end-diastolic pressures and peak V waves during cardiac catheterization both prior to and 15 min after BMV than group B patients (all p values < 0.05). In group A, nitroglycerin administration was associated with a decrease in LV end-diastolic pressure (p = 0.049), LA pressure (p < 0.001), and peak V wave (p < 0.001) that was still persistent 30 min after its administration, reaching values similar to those observed in group B early after BMV. At multivariate analysis, the only independent predictors of LV dysfunction early after BMV were found to be LV early- (p = 0.015) and end-diastolic (p = 0.023) pressures at baseline and the Wilkins' score (p = 0.004). CONCLUSIONS: After successful BMV a transient lack of LV adaptation to the increased LV preload resulting in a persistently elevated LA pressure is predicted by higher baseline LV diastolic filling pressures and higher Wilkins' scores. It is promptly and steadily reversed by nitroglycerin administration through a transient LV unloading, thus allowing a correct hemodynamic evaluation of the immediate results of the procedure.     

Heart rate acceleration without changes in the QT interval and severe ventricular tachyarrhythmias: a variant of the long QT syndrome?

We report a 48-year-old woman without demonstrable heart disease who developed ventricular tachycardia associated with increase in her heart rate without normal QT interval shortening.