*1.4. Endothelial Dysfunction and Changes in Vascular Structure*

Endothelial dysfunction plays an important role in the pathogenesis of CKD and albuminuria [50]. Insulin resistance, low levels of adiponectin, high plasma leptin, increased levels of plasma glucose, and FFAs induce an inflammation profile that causes endothelial dysfunction, which causes increased protein loss from the kidneys.

Nitric oxide (NO) is produced from the endothelium, promotes vasodilation, reduces inflammation, and platelet aggregation. Phosphoinositide 3-kinase activation is causing phosphorylation of endothelial NO synthase (e-NOs) that produce NO [51]. Obesity is associated with reduced NO bioavailability. In the presence of insulin resistance this pathway is down-regulated, while hyperinsulinemia increases endothelin-1 levels resulting in imbalance between vasodilator and vasoconstrictor endothelium factors causing hypertension [52,53]. Vascular cell adhesion molecule-1 (VCAM-1), inter-cellular adhesion

molecule-1 (ICAM-1), and E-selectin increase monocyte adhesion to the vascular wall, inducing atherosclerosis. These vascular factors promote a cycle that is causing renal damage and hypertension [33].
