# 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)  
Changes in endothelial function and increased carotid IMT and arterial stiffness are present in the early stages of the disease in young ADPKD patients and are associated with increased cardiovascular risk [5]. Endothelial cells produce more collagen and dysregulate matrix metalloproteinases as a consequence of the inflammatory status and stress factors present in ADPKD, which increase arterial stiffness. This is associated with uncontrolled arterial blood pressure and increases peripherical resistance, worsening hypertension and exposing patients to an increased rate of cardiovascular events and mortality [44]. A damaged endothelium loses its atheoprotective effect, as impaired vasomotion is responsible for the abnormal regulation of blood vessel tone [44; 45]. When endothelial dysfunction occurs, the composition of the endothelial bilayer changes: the intima-media thickness is augmented and the amount of collagen is increased, worsening arterial stiffness. The pathogenic process underlying endothelial dysfunction in ADPKD is still an object of debate, suggesting a role of the inflammatory status and vascular oxidative stress, as demonstrated by high levels of circulating NF-kB. Endothelial dysfunction is characterized by changes in the barrier permeability, which expose the vessels to aging and atherosclerosis, and by an altered vasodilitation/vasoconstr ratio, mediated by the reduction in NO [5; 45]. Endothelial dysfunction leads to the stiffness of the vessels increasing the peripherical arterial resistances, worsening arterial hypertension. Thus, endothelial dysfunction is a risk factor for cardiovascular events, such as stroke and coronary artery disease, with an increased mortality rate. Some studies suggest that the activation of RAAS, mediated by the extension of cysts, can contribute to vascular dysfunction in addition to autonomic dysfunction [43]. Figure 2: Autonomic dysfunction in autosomal dominant polycystic kidney disease. Abbreviations: SDNN: standard deviation of all sinus rhythm RR intervals; LF: low frequency, HF: high frequency, LF/HF: low frequency/high frequency, SRAA: systemic renin angiotensin aldosterone; NO: nitric oxide. In fact, the activation of RAAS, impaired NO-related vasorelaxation, increased sympathetic nerve activity, increased plasma endothelin-1 concentrations, and insulin resistance have also been observed [1; 2]. Hyperaldosteronism contributes to the further growth of cysts, renal fibrosis, and the progression of cardiorenal disease. This effect is attributed to the aldosterone-induced target organ inflammation and fibrosis and the development of metabolic syndrome. The mechanisms by which aldosterone exerts its negative effect include oxidative stress and endothelial dysfunction through the decreased synthesis and release of NO, the production of reactive oxygen species mediated by nicotinamide-adenine-dinucleotide-phosphate-oxidase-dependent mechanisms, inflammation, and fluid retention, determining vascular remodeling, hypertrophy, and fibrosis. Furthermore, aldosterone also seems to be involved in the development of metabolic syndrome, dyslipidemia, endothelial dysfunction, and insulin resistance. The majority of these effects are mediated by the activation of the mineralocorticoid receptors that are expressed in cardiomyocytes, cardiac fibroblasts, and vascular smooth muscle cells, and they are mediated by the genomic and non-genomic effects of the hormone. The mechanisms by which aldosterone may contribute to insulin resistance include the increased degradation of insulin receptor substrates, the reduced transcription of the insulin receptor gene, interference with insulin signaling mechanisms, inflammation, reduced adiponectin production, and increased oxidative stress [4; 43]. Moreover, experimental evidence suggests that PC1 and PC2 serve as mechanoreceptors in endothelial cells and smooth muscle cells, which sense the shear stress of the blood flow.