# Assessment of Cardiovascular Disease in Autosomal Dominant Polycystic Kidney Disease
## 6 Flow-Mediated Dilation (FMD), Carotid Intima-Media Thickness (IMT), and Pulse Wave Velocity (PWV)
The reduction in these glycoproteins may implicate an alteration in intracellular signaling, leading to reduced NO production. The reduction in NO may promote oxidative stress, vasoconstriction, hypoxia, and vascular remodeling, contributing to renal function decline and cardiovascular morbidity [44]. Increased oxidative stress and inflammation are other factors that contribute to the reduction in NO availability [44]. The evaluation of a possible therapy to improve endothelial-dependent vasodilation is in progress, through the brachial infusion of dopamine in normotensive APDKD patients in order to restore NO bioavailability [44]. In fact, some authors showed that the stimulation of dopamine type 5 receptor on polycystin-deficient endothelial cells restores cilia length and shear-stress-induced calcium-dependent NO release, which suggests that stimulating dopamine receptors may have beneficial effects in ADPKD patients [44]. Studies over the past 2 decades have indicated the presence of an inflammatory component in ADPKD human and murine models [45]. NOXs are enzymes present in the vascular wall, and their primary task is to produce reactive oxygen species (ROS) superoxide, at physiologically low levels, in vascular cells. Some evidence showed overactive NOX systems in the initiation and progression of vascular disease via excessive ROS production by cells of the artery wall at levels that are cytotoxic. These ROS may lead to the activation of proinflammatory pathways; the depletion of antioxidants; and oxidative damage to proteins, lipids, and DNA. Among the NOX isoforms, NOX2 is believed to have the greatest implication in vascular disease. The overexpression of NOX2 in mice results in significantly increased superoxide production, and NOX2 knockout mice show significantly reduced ROS levels. Therefore, the increased activation of NOX2 could contribute to the diminished bioavailability of NO, and thus endothelial dysfunction and vascular cell hypertrophy. NOX2 upregulation could also explain the oxidative stress observed in patients with ADPKD, including endothelial dysfunction [4; 45]. Due to the important role of the endothelium in the homeostasis of vessels, for example, in mediating vasodilation related to shear stress (increasing or decreasing the speed of blood flow), in the regulation of inflammation, it is important to detect endothelial dysfunction. Some non-invasive methods are used to detect endothelial disfunction. One of these methods is flow-mediated dilation (FMD) characterized by the evaluation of the diameter of the brachial artery before and after reactive hyperemia through the ultrasound technique. FMD is realized through the measurement of the diameter of a peripheric artery, a usual brachial artery, with a linear ultrasound transducer. The diameter of the artery is valued on a specific position at rest (baseline), then after inflation, lasting 15 s, and consequently upon the deflation of a sphygmomanometer cuff, which simulates shear stress. FMD is generally calculated as FMD (%) = (Peak diameter - baseline diameter)/(baseline diameter) [43]. After this shear stress factor, endothelia should produce NO to stimulate vasodillatation and then reactive hyperemia. In ADPKD patients, there is endothelium dysfunction in the inflammatory state, with low NO available and increased arterial stiffness worsening flow-mediated vasodillatation [44; 45; 46; 47; 48; 49]. A meta-analysis of 27 studies, including a total of 1967 ADPKD patients with preserved renal function (eGFR > 60/mL/min/1.73 m\({}^{2}\)) compared to healthy controls, showed increased vascular stiffness and endothelial disfunction in patients with ADPKD. These damages were already present at the early stage of renal disease [46]. In particular, FMD was estimated to be significantly lower in ADPKD patients compared to healthy controls. ADPKD was also linked to significantly higher pulse wave velocity (PWV) and carotid IMT with the stiffening of large elastic arteries, contributing to cardiovascular dysfunction [46].