The association of cardiovascular events with Lp-PLA2 has been studied continuously today. The enzyme has been strongly associated with several cardiovascular risk markers and events. Its discovery was directly related to the hydrolysis of the platelet-activating factor and oxidized phospholipids, which are considered protective functions. However, the hydrolysis of bioactive lipids generates lysophospholipids, compounds that have a pro-inflammatory function. Therefore, the evaluation of the distribution of Lp-PLA2 in the lipid fractions emphasized the dual role of the enzyme in the inflammatory process, since the HDL-Lp-PLA2 enzyme contributes to the reduction of atherosclerosis, while LDL-Lp-PLA2 stimulates this process. Recently, it has been verified that diet components and drugs can influence the enzyme activity and concentration. Thus, the effects of these treatments on Lp-PLA2 may represent a new kind of prevention of cardiovascular disease. Therefore, the association of the enzyme with the traditional assessment of cardiovascular risk may help to predict more accurately these diseases.

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Oxidative modifications in lipoproteins (LP), especially in low-density lipoproteins (LDL), are associated with initiation and progression of atherosclerosis. The levels of a sub-fraction of LDL with oxidative characteristics, named electronegative LDL [LDL(-)], minimally oxidized LDL, and minus LDL, are known to be increased in subjects with familial hypercholesterolemia, hypertriglyceridemia, nonalcoholic steatohepatitis, diabetes mellitus, coronary artery disease, patients undergoing hemodialysis, and athletes after aerobic exercise. In addition to the oxidative profile, physical and biological characteristics of LDL(-) consist of nonenzymatic glycosylation, increased expression and activity of platelet-activating factor acetylhydrolase (PAF-AH) and phospholipase A(2) (PLA(2)), enriched NEFA content, hemoglobin and ApoB-100 cross-linking, and increase in ApoC-III and ApoE in LDL. Herein, we summarize the state of the art of the up-to-date body of knowledge on the possible origin and impact of LDL(-) in health and disease. Further, the potential perspectives of using LDL(-) as a biomarker in conditions under metabolic stress are also discussed.

The aim of this study was to assess the relationship between homocysteine (tHcy), folate and vitamin B12 levels, urinary albumin excretion, and arterial blood pressure in patients with non-insulin-dependent diabetes mellitus (NIDDM). Our study was carried out in 33 NIDDM patients (16 men, 17 women) and 16 healthy volunteers as controls (seven men, nine women). Fasting and postmethionine load plasma tHcy levels were assessed, together with folate, vitamin B12, and urinary albumin excretion levels. In NIDDM patients, there were correlations between folate and mean arterial pressure (r = -0.352, P = .046), folate and systolic blood pressure (r = -0.437, P = .013), folate and vitamin B12 (r = 0.499, P = .004), tHcy and vitamin B12 (r = -0.348, P = .04), ln tHcy and ln folate (r = -0.404, P = .01), and, lastly, between tHcy, either fasting or postload, and urinary albumin excretion. Patients with elevated tHcy levels had significantly higher diastolic blood pressure (P = .04) and mean arterial pressure (P = .03). Otherwise, higher folate values were associated with lower systolic blood pressure (P = .004) and mean arterial pressure (P = .02). In addition, NIDDM patients with complications presented higher tHcy basal values than the group without complications (P = .003). A particular propensity of such patients towards endothelial dysfunction could explain the presence of correlations between these metabolic parameters and arterial blood pressure.

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OBJECTIVEThe pathogenesis of brain disorders in type 1 diabetes (T1D) is multifactorial and involves the adverse effects of chronic hyperglycemia and of recurrent hypoglycemia. Kidney-pancreas (KP), but not kidney alone (KD), transplantation is associated with sustained normoglycemia, improvement in quality of life, and reduction of morbidity/mortality in diabetic patients with end-stage renal disease (ESRD).RESEARCH DESIGN AND METHODSThe aim of our study was to evaluate with magnetic resonance imaging and nuclear magnetic resonance spectroscopy (1H MRS) the cerebral morphology and metabolism of 15 ESRD plus T1D patients, 23 patients with ESRD plus T1D after KD (n = 9) and KP (n = 14) transplantation, and 8 age-matched control subjects.RESULTSMagnetic resonance imaging showed a higher prevalence of cerebrovascular disease in ESRD plus T1D patients (53% [95% CI 36–69]) compared with healthy subjects (25% [3–6], P = 0.04). Brain 1H MRS showed lower levels of N-acetyl aspartate (NAA)-to-choline ratio in ESRD plus T1D, KD, and KP patients compared with control subjects (control subjects vs. all, P < 0.05) and of NAA-to-creatine ratio in ESRD plus T1D compared with KP and control subjects (ESRD plus T1D vs. control and KP subjects, P ≤ 0.01). The evaluation of the most common scores of psychological and neuropsychological function showed a generally better intellectual profile in control and KP subjects compared with ESRD plus T1D and KD patients.CONCLUSIONSDiabetes and ESRD are associated with a precocious form of brain impairment, chronic cerebrovascular disease, and cognitive decline. In KP-transplanted patients, most of these features appeared to be near normalized after a 5-year follow-up period of sustained normoglycemia.

OBJECTIVEIslets after kidney transplantation have been shown to positively affect the quality of life of individuals with type 1 diabetes (T1D) by reducing the burden of diabetes complications, but fewer data are available for islet transplantation alone (ITA). The aim of this study was to assess whether ITA has a positive impact on hemostatic and cerebral abnormalities in individuals with T1D.RESEARCH DESIGN AND METHODSProthrombotic factors, platelet function/ultrastructure, and cerebral morphology, metabolism, and function have been investigated over a 15-month follow-up period using ELISA/electron microscopy and magnetic resonance imaging, nuclear magnetic resonance spectroscopy, and neuropsychological evaluation (Profile of Mood States test and paced auditory serial addition test) in 22 individuals with T1D who underwent ITA (n = 12) or remained on the waiting list (n = 10). Patients were homogeneous with regard to metabolic criteria, hemostatic parameters, and cerebral morphology/metabolism/function at the time of enrollment on the waiting list.RESULTSAt the 15-month follow-up, the group undergoing ITA, but not individuals with T1D who remained on the waiting list, showed 1) improved glucose metabolism; 2) near-normal platelet activation and prothrombotic factor levels; 3) near-normal cerebral metabolism and function; and 4) a near-normal neuropsychological test.CONCLUSIONSITA, despite immunosuppressive therapy, is associated with a near-normalization of hemostatic and cerebral abnormalities.

Summary Obesity has increased in children and adolescents. What is reflected in the early occurrence of cardiometabolic alterations, like hypertension and type 2 diabetes, where the oxLDL formation is stimulated. Various studies have shown that plasma a-tocopherol (a-TP) can protect LDL against oxidation. Nevertheless, the action of plasma a-TP in cardiovascular diseases remains controversial. We conducted a cross-sectional study to evaluate plasma a-TP and its impact on the concentration of LDL(2). Adolescents (n5150) of both sexes were classified into three groups: healthy weight (HW; 50%), overweight (OV; 22%), and obese (OB; 28%). Lipid profile, LDL(2), anti-oxLDL and anti-LDL(2) antibodies, CRP (ELISA) and plasma a-TP (HPLC) were analyzed. Demographic, anthropometric, and food intake data were evaluated. Crude and energy-adjusted intake of vitamin E in the OB group were higher than in the HW group (p,0.001). Crude and energy-adjusted vitamin E intakes were not correlated with plasma a-TP (r520.07; p50. 412 and r520.064; p50.467, respectively). Subjects in the OB group had higher TC and LDL-C and lower HDL-C than in the HW and OV groups. C-reactive protein and anti-oxLDL antibodies changed as a function of BMI. The impact of obesity was reinforced by high values for LDL(2) and low content of plasma a-TP in comparison with the HW (p,0.001) and OV groups (p50.03). This negative profile was maintained for the ratio between a-TP and TC or LDL-C. Plasma a-TP, a-TP/TC and a-TP/LDL-C were negatively associated with LDL(2) and other cardiometabolic risk factors (BMI, WC, AC and anti-oxLDL). Our results demonstrate that obesity in adolescents is associated with high levels of LDL(2) and low plasma a-TP content.