Central role of obesity in endothelial cell dysfunction and cardiovascular risk

SUMMARY Atherosclerosis is the leading cause of mortality in the contemporary world. The critical role of the endothelial cells (EC) in vascular homeostasis, the metabolic changes that take place when the cell is activated, and the elements involved in these processes have been widely explored over the past years. Obesity and its impact, promoting a rise in blood levels of free fatty acids (FAs) are often associated with atherosclerosis and cardiovascular mortality. However, the mechanisms that promote cardiovascular structural changes and adaptive changes in the ECs, particularly in the context of obesity, are little known. Here, we reviewed studies that assessed the metabolic adaptations of healthy and dysfunctional ECs during exposure to FAs, as well as the epidemiological perspectives of cardiovascular structural changes in obesity. Finally, we explored the role of new agents - sphingolipids, dietary unsaturated fatty acids and sodium-glucose cotransporter-2 inhibitors (iSGLT2) - in atherosclerosis and their relationship with obesity.

RESUMO A aterosclerose é a causa líder de mortalidade no mundo contemporâneo. O papel central da célula endotelial (EC) na homeostase vascular, as alterações metabólicas que ocorrem quando a célula se torna ativada e os elementos envolvidos nesses processos vêm sendo bastante explorados nos últimos anos. A obesidade e o seu impacto, promovendo uma elevação dos níveis sanguíneos de ácidos graxos (FAs) livres, é bastante associada à aterosclerose e à mortalidade cardiovascular. Entretanto, os mecanismos que promovem alterações estruturais cardiovasculares e alterações adaptativas nas ECs, particularmente no contexto da obesidade, são pouco conhecidos. Aqui, nós revisamos estudos que avaliaram as adaptações metabólicas das ECs normais e disfuncionais durante exposição a FAs, bem como as perspectivas epidemiológicas das alterações cardiovasculares estruturais na obesidade. Finalmente, exploramos o papel de novos atores — esfingolípides, ácidos graxos insaturados da dieta e inibidores do cotransportador de sódio-glucose 2 (iSGLT2) — na aterosclerose e sua relação com a obesidade.

Adiponectin concentration data improve the estimation of atherosclerotic risk in normal and in overweight subjects

BACKGROUND: The combinations of adipokines and body mass parameters to estimate carotid atherosclerotic disease have not been completely delineated. OBJECTIVE: To test the combinations of well-established, easily accessible body mass indices and circulating biomarkers to identify increased carotid intima-media thickness (cIMT) in a primary prevention setting. DESIGN AND PATIENTS: In a cross-sectional analysis of 339 asymptomatic individuals with no history of cardiovascular events, inflammatory and insulin sensitivity biomarkers as well as adipokine levels were measured and combined with body mass parameters to evaluate the best marker for increased cIMT.RESULTS: As isolated parameters, body mass index (BMI) and adiponectin best identified abnormal cIMT (P = .04). Adiponectin levels were also linked to the relationship between BMI and cIMT (β = 0.0371; P = .01). Twenty-nine individuals with increased cIMT were missed by BMI alone but detected by combining BMI and adiponectin measurements. When compared with BMI alone, the combination of adiponectin plus BMI improved the c-statistic (0.549-0.567) and the integrated discrimination improvement index (0.01725; P = .021). Segregation of individuals by the combined use of BMI + adiponectin is associated with significant differences in insulin sensitivity, glomerular filtration rate, systemic inflammatory activity, dyslipidaemia and cIMT.