Treatment with a Toll-like Receptor 7 ligand evokes protective immunity against atherosclerosis in hypercholesterolaemic mice.

BACKGROUND: The interplay between innate and adaptive immunity is central in life-threatening clinical complications of atherosclerosis such as myocardial infarction and stroke. The specific mechanisms involved and their protective versus detrimental effects in the disease process remain poorly understood. We have previously shown that higher levels of Toll-like receptor 7 (TLR7) expression in human atherosclerotic lesions are correlated with better patient outcome. OBJECTIVE: In this study, we explored whether TLR7 activation can ameliorate disease in experimental atherosclerosis in mice. METHODS: Apolipoprotein E deficient mice (Apoe-/- ) with established disease were injected for five weeks intraperitoneally with the TLR7 ligand R848. Local effects were evaluated by characterization of the lesion. Systemic effects of the treatment were investigated by immune composition analysis in the spleen and plasma measurements. RESULTS: The in vivo treatment arrested lesion progression in the aorta. We also detected expansion of marginal zone B cells and Treg in the spleen together with increased plasma IgM antibodies against oxidized low-density lipoprotein (oxLDL) and reduced plasma cholesterol levels. These changes were accompanied by increased accumulation of IgM antibodies, decreased necrosis and fewer apoptotic cells in atherosclerotic lesions. CONCLUSIONS: Our findings show that TLR7 stimulation could ameliorate atherosclerotic lesion burden and reduce plasma cholesterol in Apoe-/- mice. TLR7 stimulation was associated with an atheroprotective B-cell and Treg response, which may have systemic and local effects within lesions that could prevent arterial lipid accumulation and inflammation.

Neural reflex control of vascular inflammation.

Atherosclerosis is a multifactorial chronic inflammatory disease that underlies myocardial infarction and stroke. Efficacious treatment for hyperlipidemia and hypertension has significantly reduced morbidity and mortality in cardiovascular disease. However, atherosclerosis still confers a considerable risk of adverse cardiovascular events. In the current mechanistic understanding of the pathogenesis of atherosclerosis, inflammation is pivotal both in disease development and progression. Recent clinical data provided support for this notion and treatment targeting inflammation is currently being explored. Interestingly, neural reflexes regulate cytokine production and inflammation. Hence, new technology utilizing implantable devices to deliver electrical impulses to activate neural circuits are currently being investigated in treatment of inflammation. Hopefully, it may become possible to target vascular inflammation in cardiovascular disease using bioelectronic medicine. In this review, we discuss neural control of inflammation and the potential implications of new therapeutic strategies to treat cardiovascular disease.

Transcutaneous carbon dioxide measurements in the fetus during labor.

Continuous transcutaneous carbon dioxide partial pressure (tcPco2) was monitored in 40 spontaneous labors. The electrode was attached by glue fixation. An interpretable tracing was obtained in 36 cases. All cases but 2 were normal pregnancies. Thirty-two patients had epidural analgesia while the others had no analgesia. All infants had an Apgar score above 7 at five minutes after delivery and only two had a pH of the umbilical artery of less than 7.16. Mean duration of the recordings was 116 minutes (range: 15-300) and mean time for reaching steady-state was 27 minutes (range: 10-45 minutes). Mean value of tcPco2 was 48 mmHg (SD: 6) before 6 cm of dilatation, 47 mmHg (SD: 8) between 6 and 10 cm, and 47 mmHg (SD: 15) at the second stage of labor. Mean umbilical artery Pco2 was 48 mmHg (SD: 14) and mean umbilical artery pH was 7.25 (SD: 0.06). The range of tcPco2 obtained in these normal cases was 20 to 62 mmHg. Comparison of the results with those of other authors and with previous studies of normal labor and epidural analgesia show a higher tcPco2 compared to scalp Pco2. In contrast to other studies in these series no correlation was found in the series between umbilical artery Pco2 and tcPco2 values. This lack of correlation could be explained either by the small number of cases in which both measurements were available (9 cases) and by the small range of variation or by some inaccuracy in the measurements.(ABSTRACT TRUNCATED AT 250 WORDS)