Increased Plasma Urotensin-II and Carotid Atherosclerosis are Associated with Vascular Dementia

Abstract

Aim: Human urotensin-(U ) is a cyclic neuropeptide with potent vasoconstrictive activity in the vasculature. The expression of U and its receptor (UT) mRNA is detected at high levels in the brain. We evaluated the relationship between plasma U levels and vascular dementia (VaD) caused by stroke or atherosclerotic small vessel disease. Methods: Carotid artery intima-media thickness (IMT), plaques, plasma levels of immunoreactive U (IR-U ), and atherosclerotic biomarkers were determined in 42 patients with VaD, 197 with Alzheimer's disease (AD), and 47 non-demented elderly controls. Results: Age, gender, body mass index, systolic blood pressure (SBP), fasting plasma glucose, insulin, triglycerides, high-density lipoprotein cholesterol, leptin, and plasminogen activator inhibitor-1 levels were not significantly different among these groups. IR-U , low-density lipoprotein (LDL) cholesterol, lipoprotein(a), lipid peroxides, interleukin-6, and high-sensitive C-reactive protein (hs-CRP) levels, and maximum IMT were significantly higher in VaD than in AD patients or controls. IR-U level showed a significantly positive correlation with SBP or maximum IMT. Multivariate logistic regression analysis revealed a significantly independent association between IR-U levels or increased maximum IMT ( ≥ 1.1 mm) and VaD as compared with SBP, LDL cholesterol, and interleukin-6 levels. Conclusion: Increased plasma IR-U levels and carotid atherosclerosis may be involved in the pathogenesis and progression of VaD.

Genetic and Pharmacological Manipulation of Urotensin II Ameliorate the Metabolic and Atherosclerosis Sequalae in Mice

“…33 Moreover, elevated plasma level of UII and expression of UII and the UT have been reported in experimental animals of hypertension, 34,35 and a recent study has shown significant correlation between blood pressure and UII levels in patients with carotid atherosclerosis and vascular dementia. 36 Here we demonstrated that UII KO mice tend to exhibit decreased mean arterial and, particularly, systolic blood pressure than wild type. Similarly, the use of UT antagonist SB657510A significantly reduced mean blood pressure and systolic pressure in apoE KO mice fed a HFD.…”

“…UII has been shown to influence lipase activity in the cohoe salmon, 38,39 and UII plasma level is associated with LDL in atherosclerosis. 36 However, since those initial studies, little has been done to assess the effects of UII on serum lipids. Here, we demonstrated for the first time that deletion of the UII gene alone or in the pathological setting of apoE KO in mice fed a HFD resulted in a decrease in serum LDL and triglycerides and an increase in serum pre-β highdensity lipoprotein as evident in the increase of lipoprotein particles containing apoA-I.…”

Evaluation of serum urotensin-II levels of children with attention deficit hyperactivity disorder and autism spectrum disorder

“…20 In a similar context, U-II might have different effects on the various regions of brain, and because of this variability, U-II could play a role in the etiologies of different neuropsychiatric disorders.…”

“…Furthermore, there was no reported association between Alzheimer's and U-II levels. 20 These findings indicate that U-II could play a role in vascular dementia's etiology via severe vasoconstriction. U-II is also an important molecule for understanding the brain's blood supply, as well as oxidative and immunological mechanisms.…”

“…U-II is also an important molecule for understanding the brain's blood supply, as well as oxidative and immunological mechanisms. 20,21 Oxidative and immunologic mechanisms are also subjected to playing role in the etiology of ADHD and ASD. 22,23 In this context, it worths to analyze that if U-II levels have an effect on microcirculation and this might have an important aspect in the etiology of ASD or ADHD.…”