Tumor Necrosis Factor-α Antagonism Improves Vasodilation During Hyperinsulinemia in Metabolic Syndrome

OBJECTIVE—Obesity is associated with chronic inflammation due to overproduction of proinflammatory cytokines, including tumor necrosis factor (TNF)-α. We assessed the effects of TNF-α neutralization by infliximab on vascular reactivity during hyperinsulinemia in obesity-related metabolic syndrome

MicroRNA in ischemic stroke etiology and pathology

Small, noncoding, microRNAs (miRNAs) have emerged as key mediators of posttranscriptional gene silencing in both pathogenic and pathological aspects of ischemic stroke biology. In stroke etiology, miRNA have distinct expression patterns that modulate pathogenic processes including atherosclerosis (miR-21, miR-126), hyperlipidemia (miR-33, miR-125a-5p), hypertension (miR-155), and plaque rupture (miR-222, miR-210). Following focal cerebral ischemia, significant changes in the miRNA transcriptome, independent of an effect on expression of miRNA machinery, implicate miRNA in the pathological cascade of events that include blood brain barrier disruption (miR-15a) and caspase mediated cell death signaling (miR-497). Early activation of miR-200 family members improves neural cell survival via prolyl hydroxylase mRNA silencing and subsequent HIF-1α stabilization. Pro- (miR-125b) and anti-inflammatory (miR-26a, -34a, -145, and let-7b) miRNA may also be manipulated to positively influence stroke outcomes. Recent examples of successfully implemented miRNA-therapeutics direct the future of gene therapy and offer new therapeutic strategies by regulating large sets of genes in related pathways of the ischemic stroke cascade

Nota su Libero de libero.

New genetic evidence strongly supports a role for the immune system in the pathogenesis of essential hypertension (EH) through chemokines and their receptors (CCR) involvement. The aim of the present study was to evaluate the possible relation between CCR2 and CCR5 alleles and blood pressure (BP) levels in hypertensive subjects. In all, 118 essential hypertensive outpatients (male 90, female 28; stage I and II; age 27-54 years; not previously treated with antihypertensive drugs) were selected for the study. All of the subjects underwent office BP measurement. Subsequently, 24-h ambulatory BP monitoring (ABPM) was performed with a Spacelabs 90207 monitor during a regular working day. CCR264I and CCR5.32 polymorphisms were determined by polymerase chain reaction (PCR), following the standard molecular biology protocols. Allelic frequencies were the following: CCR5 Delta 32 = 0.097, CCR264I = 0.101. Logistic regression analysis showed an association between the CCR5 Delta 32 allele and the following: 24-h systolic BP (SBP > 140 mmHg; p = 0.027), values over the 50th percentile of 24-h SBP (p = 0.032), and the values over the 50th percentile of nighttime SBP (p = 0.039). Office BP showed an association with the Delta 32 allele in a range over the 75th percentile of SBP (p = 0.087) and the 75th percentile of DBP (p = 0.085). No significant association was observed for CCR264I and BP levels or between physiological nocturnal BP decline and genotype. The observed results not only support the role of the immune system in the development and maintenance of hypertension, but they also indicate an influence of CCR5 Delta 32 polymorphism on the establishment of BP levels