Microparticle miRNAs as Biomarkers of Vascular Function and Inflammation Response to Aerobic Exercise in Obesity?

OBJECTIVE: This study aimed to explore the role of nine microRNAs (miRNAs) in microparticles (MPs) on the efficacy of aerobic exercise in the regulation of inflammation and vascular function in obesity. METHODS: Sedentary women with normal weight (n = 6, BMI < 25 kg/m2 ) and women with obesity (n = 9, BMI > 30 kg/m2 ) were recruited at F. Hached Hospital (Sousse, Tunisia) and enrolled in an 8-week aerobic program. Vascular function was assessed using laser Doppler flowmetry/iontophoresis, circulating MPs by flow cytometry, miRNAs by real-time polymerase chain reaction, and inflammation by ELISA, before and after exercise. RESULTS: Women with obesity presented with high prevalence of cardiovascular risk factors and a higher circulating MP level compared with healthy subjects. The MP miRNA profile was significantly different in the two groups. Exercise reduced BMI and inflammation in both groups and significantly improved endothelial-dependent response (acetylcholine cutaneous vascular conductance) for healthy subjects, with a trend for women with obesity. Circulating MP level was increased after exercise, and miRNA expression was differentially modulated in both populations. Pearson analysis revealed a correlation between MPs miR-124a and miR150 and adiponectin, TNFα, or IL-6 levels. CONCLUSIONS: The relation between MPs and miRNA profile, inflammation, vascular function, and exercise is of particular interest for defining "miRNA biomarker signature" in patients with cardiovascular disease who are potentially susceptible to respond to exercise.

Functional G894T (rs1799983) polymorphism and intron-4 VNTR variant of nitric oxide synthase (NOS3) gene are susceptibility biomarkers of obesity among Tunisians.

OBJECTIVE: The endothelial nitric oxide synthase (NOS3) has been shown to play a role in the modulation of lipolysis. The goal of this study was to examine the impact of the G894T (rs1799983) and a 27 bp variable number of tandem repeats (VNTR 4a/b) of NOS3 gene on obesity in a sample of the Tunisian population. RESEARCH METHODS AND PROCEDURES: The study included 211 normal weight subjects and 183 obese patients. NOS3 G894T and 4a/b variants were determined by PCR analysis and examined for association with obesity-related traits. The effect of obesity on forearm skin blood flow (FSBF) response to acetylcholine, an endothelium-dependent vasodilator was determined by laser Doppler iontophoresis. RESULTS: In case-control studies, both G894T and 4a/b variants were associated with obesity. A significantly increased risk of obesity was found with the NOS3(G894T) TT genotype (OR:2.62, P=0.04). This association remains significant after adjustments for age and gender (OR: 2.93, P=0.03). A higher risk was also observed for carriers of the G894T allele (OR: 1.72, P=0.001). Stratified analysis by gender revealed that obese men (but not women) had significantly higher frequency of TT genotypes compared to controls (9.9% vs. 2.9%, P=0.01). Carriers of the 4b allele presented a significantly higher risk of obesity than non-carriers even after adjustments for age and gender (OR (95%CI): 1.72 (1.16-2.56), P=0.004). Correlations with anthropometric parameters revealed that carriers of TT and bb genotypes had significantly higher body mass index compared to those homozygous for the G and a alleles (P=0.0004). CONCLUSION: This study provides the first evidence for the association of G894T and 4a/b variants with body mass index and the risk of obesity in Tunisians. These polymorphisms did not exhibit, however any significant association with both metabolic traits and vascular function.

Role of eNOS- and NOX-containing microparticles in endothelial dysfunction in patients with obesity.

OBJECTIVE: To explore the pathophysiological profile of patients who have obesity and to investigate the potential role of circulating microparticles (MPs) in endothelial dysfunction in patients who have obesity. METHODS: The inflammatory and oxidative status and the cutaneous microvascular blood flow were characterized in 69 patients with android obesity and 46 subjects with normal weight (controls) by using laser Doppler flowmetry. Circulating MP levels were measured by flow cytometry, and endothelial nitric oxide synthase (eNOS) and NADPH oxidase (NOX) expression in MPs was investigated by Western blotting. MP effect on vascular reactivity was assessed in rat aorta rings. RESULTS: Patients with obesity showed endothelial dysfunction, hyperglycemia, inflammation, and oxidative stress. In controls, low MP levels were positively correlated with normal microvascular function. Western blot analysis revealed reduced eNOS and increased NOX4D expression in MPs from subjects with obesity compared with controls. However, this was not correlated with endothelial dysfunction parameters and did not impair ex vivo endothelium-dependent vasodilation. CONCLUSIONS: These results suggest that MPs do not contribute directly to endothelial dysfunction associated with obesity. Conversely, eNOS- and NOX-containing MPs could be involved in the compensatory mechanism of vascular endothelial cells to counteract the pathologic mechanisms underlying endothelial dysfunction.

[Towards a better knowledge of breast cancer physiopathology: the proteomics approach]. / Pour une meilleure compréhension de la physiopathologie des cancers mammaires : l'approche protéomique.

Breast cancer represents a major public health problem. Approximately one woman in ten is likely to develop a malignant tumor of the breast in their lifetime. The frequency of breast cancer is rising steadily for 20 years and the practical benefits in the diagnosis, prognosis and treatment of this disease are still too limited. Actually, there is no tumor marker with a specificity and sensitivity sufficient to have an utility in clinical and early diagnosis of breast cancer, although, carcinoembryonic antigen (CEA), MUC-1 and CA 15-3 were reported to be useful as markers for monitoring this disease. Thus, proteomics approaches are needed for the discovery and the identification of new protein biomarkers that may allow a better understanding of biological mechanisms of breast tumor development and serve as potential therapeutic targets. This article reviews advances in this field, as well as, the major contribution of these markers in breast pathology, with a focus on their biological characteristics and their clinical and therapeutic involvement.