Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE) have accelerated atherosclerosis. The underlying mechanisms are poorly understood, and investigations have been hampered by the absence of animal models that reflect the human condition of generalized atherosclerosis and lupus. We addressed this problem by transferring lupus susceptibility to low-density lipoprotein (LDL) receptor-deficient (LDLr-/-) mice, an established model of atherosclerosis, creating radiation chimeras with NZM2410-derived, lupus-susceptible, B6.Sle1.2.3 congenic or C57BL/6 control donors (LDLr.Sle and LDLr.B6, respectively). LDLr.Sle mice developed a lupus-like disease characterized by production of double-stranded DNA autoantibodies and renal disease. When fed a Western-type diet, LDLr.Sle chimeras had increased mortality and atherosclerotic lesions. The plaques of LDLr.Sle mice were highly inflammatory and contained more CD3+ T cells than controls. LDLr.Sle mice also had increased activation of CD4+ T and B cells and significantly higher antibody to oxidized LDL and cardiolipin. Collectively, these studies demonstrate that the lupus-susceptible immune system enhances atherogenesis and modulates plaque composition.     

Transiently heightened angiotensin II has distinct effects on atherosclerosis and aneurysm formation in hyperlipidemic mice

Experimentally sustained increase in angiotensin II (AngII) promotes tissue destruction in various cardiovascular disorders. We examined whether transiently heightened AngII affects subsequent atherosclerosis and aneurysm formation. AngII or saline was administered for 2 weeks to apolipoprotein E (apoE)-deficient mice. Mice were sacrificed at the end of the 2-week infusion or 6- or 14 weeks later. Short-term AngII did not affect atherosclerosis immediately following the infusion or 6 weeks later. By contrast, 14 weeks after infusion there was remarkably more atherosclerosis in previously AngII-exposed mice. Preceding the build up of atherosclerotic lesions, AngII-exposure increased mRNA expression and immunostaining of monocyte chemoattractant protein-1 (MCP-1) and its receptor, CCR2. This was followed by greater macrophage-positivity in AngII-exposed aortae. In contrast to the delayed effects on atherosclerosis, 20% of mice were found to have abdominal aneurysms at the end of AngII-exposure. This effect was not contingent on blood pressure. Moreover, despite amplification in atherosclerosis following AngII, no aneurysms were found 14 weeks later. Our studies reveal that even transient exposure to AngII primes the vessel for subsequent amplification of atherosclerosis which involves activation of MCP-1/CCR2 and influx of macrophages into the nascent atherosclerotic plaque. By contrast, transient AngII-exposure causes prompt aneurysm formation that does not parallel atherosclerosis and disappears even in the face of progressively greater atherosclerotic lesions.     

Risk of recurrence of subdural hematoma after EMMA vs surgical drainage – Systematic review and meta-analysis

ObjectiveChronic subdural hematoma (CSDH) is a common and debilitating neurological condition whose treatments, including burr hole drainage and craniotomy, suffer from high rates of recurrence and complication. Embolization of the middle meningeal artery (EMMA) is a promising minimally invasive approach to manage CSDH in a broad set of patients.MethodsTo evaluate the efficacy and safety of EMMA, a database search was conducted including the terms “subdural hematoma; embolization; embolized; middle meningeal” was performed and yielded a total of 260 results. Following exclusion based on predefined criteria, a total of four studies were identified and outcomes including recurrence rates and complication rates were extracted for analysis.ResultsFour studies including intervention and control groups were included with a total of n = 888 patients. The relative risk of CSDH recurrence in the EMMA (3.5%) compared to control group (23.5%) was significantly reduced when EMMA was performed (risk ratio = 0.17; 95% confidence interval (CI) 0.05–0.67). In addition, rates of complication were not significantly different between patients with conventional therapy and those who received EMMA (OR = 0.77; 95 confidence interval (CI) 0.3–1.99).ConclusionBased on limited data, EMMA reduces the risk of recurrence by 20% compared to surgical treatment for CSDH.     

Impact of early ventricular unloading on exercise performance in preadolescents with single ventricle Fontan physiology.

OBJECTIVES: We sought to determine if early ventricular volume unloading improves aerobic capacity in patients with single ventricle Fontan physiology. BACKGROUND: Surgical strategies for patients with single ventricle include intermediate staging or early Fontan completion to reduce the adverse affects of prolonged ventricular volume load. The impact of this strategy on exercise performance has not been evaluated. METHODS: Retrospectively, we reviewed the exercise stress test results of all preadolescents with single ventricle Fontan physiology. "Volume unloading" was considered to have occurred at the time of bidirectional cavopulmonary anastomosis or at the time of Fontan surgery in those patients who did not undergo intermediate staging. Potential predictors of aerobic capacity were analyzed using multivariate regression. RESULTS: The patients (n = 46) achieved a mean percentage predicted of maximal oxygen consumption (VO2max) of 76.1% +/- 21.1%. The mean age at the time of volume unloading was 2.7 +/- 2.4 years, and the mean age at testing was 8.7 +/- 2 years. Intermediate staging was performed in 16 of 46 patients (35%). In multivariate analysis, younger age at volume unloading was associated with increased aerobic capacity (p = 0.003). Other variables were not predictive. The subgroup of patients who underwent volume unloading before two years of age achieved a mean percentage predicted VO2max of 88.6% +/- 24.1%. CONCLUSIONS: Preadolescents with single ventricle who undergo volume unloading surgery at an early age demonstrate superior aerobic capacity compared with those whose surgery is delayed until a later age.     

Emery-dreifuss humeroperoneal muscular dystorphy: An X-linked myopathy with unusual contractures and bradycardia

Clinical, electromyographic, and muscle biopsy findings in the two largest known families with emery-Dreifuss humieroperoneal muscular dystorphy indicate that this is an X-linked recessive muscle disease with stereotyped clinical manifestations but with variable pathological and electromyographic characteristics. Elbow contractures, involvement of humeral muscles, Hyporeflexia, and abnorman electorcardiograms are present in our patients. The disorder is associated with a potentially lethal cardiac arrhythmia that should be managed by pacemaker insertion. The skeletal muscle disease is slowly progressive and is usually not life threatening. Muscle biopsy commonly shows type I fiver atrophy. Electromyogrphy usually indicates myopathy, though the classic findings of myopathy may not be present in every muscle.     

Correlates of high serum C-reactive protein levels in a socioeconomically disadvantaged population

Individuals from low socioeconomic backgrounds are disproportionately affected by the burden of cardiovascular disease (CVD), yet data regarding risk factors in this population are lacking, particularly regarding emerging biomarkers of CVD such as C-reactive protein (CRP). We measured high-sensitivity CRP and examined its association with demographic and lifestyle factors in a sample of 792 participants aged 40-79 years from the Southern Community Cohort Study, which has an over-representation of socioeconomically disadvantaged individuals (over 60% with a total annual household income < USD15,000). We found that within this population the prevalence of elevated CRP (>3 mg/L) varied significantly by sex, race, smoking status, and body mass index (BMI). The multivariable-adjusted prevalence odds ratios (ORs) (95% CIs) for having elevated CRP were 1.6 (1.1-2.3) for women vs. men, 1.4 (0.9-2.0) for African Americans vs. whites, 2.3 (1.4-3.8) for African American women vs. white men, 1.8 (1.2-2.7) for current smokers vs. non-smokers, and 4.2 (2.7-6.6) for obese (BMI 30.0-44.9 kg/m;{2}) vs. healthy-weight (BMI 18.3-24.9 kg/m;{2}) participants. Further stratified analyses revealed that the association between BMI and elevated CRP was stronger among African Americans than whites and women than men, with prevalence ORs (95% CI) comparing obese vs. healthy-weight categories reaching 22.8 (7.1-73.8) for African American women. In conclusion, in this socioeconomically disadvantaged population, sex, race, smoking, and BMI were associated with elevated CRP. Moreover, inflammatory response to obesity differed by race and sex, which may contribute to CVD disparities.