endothelin-1 and Leukoaraiosis

Leukoaraiosis (LA), as an age-related white matter degeneration, is mainly caused by chronic ischemia. Our study aims to explore the efficacy of different doses of atorvastatin (ATV) in the vascular endothelial function in patients with LA.. Our study enrolled 402 LA patients who were then randomly included as control or treated with ATV (10 mg), ATV (20 mg), or ATV (30 mg). The total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were detected by enzyme colorimetric assay. The high-sensitivity C-reactive protein (hs-CRP) level, reactive hyperemia index (RHI), endothelin-1 (ET-1) content, and nitric oxide (NO) level were tested by latex agglutination test, peripheral arterial tonometry technology, radioimmunoassay, and nitrate reductase assay, respectively.. After 8 weeks of ATV treatment, the levels of TC, LDL-C, and HS-CRP decreased significantly, and the trends were demonstrated in a more significant way with the increases of dose of ATV. The treatment with ATV at different doses elevated NO level and RHI and declined ET-1 content. Gastrointestinal reaction, muscular pain, and increased aminopherase were observed after treatment with the ATV at different doses with more obvious symptoms detected accompanied by the increase of the dose. The RHI was in negative correlation with the ET-1 and HS-CRP while in positive correlation with NO.. Our study demonstrates that ATV can significantly improve the vascular endothelial function in LA patients with a dose-dependent effect.

Topics: Adult; Aged; Aged, 80 and over; Atorvastatin; C-Reactive Protein; Case-Control Studies; Cholesterol; Cholesterol, LDL; Dose-Response Relationship, Drug; Endothelin-1; Endothelium, Vascular; Female; Humans; Latex Fixation Tests; Leukoaraiosis; Magnetic Resonance Imaging; Male; Middle Aged; Nitric Oxide

Endothelial dysfunction has been implicated in the pathogenesis of cerebral small-vessel disease (SVD). Endothelin (ET), released by the endothelium, plays a crucial role in vasoconstriction in the cerebral circulation and could contribute to the pathogenesis of cerebral SVD. Circulating ET levels may not reflect vascular production of endothelin-1 (ET-1), most of which is abluminal. Studying genetic associations, particularly of functional polymorphisms that alter activity of the ET system, is an attractive method of determining whether ET plays a role in SVD pathogenesis. We determined whether genetic variants in components of the ET system are a risk factor for cerebral SVD.. Three hundred SVD patients and 600 community controls were genotyped. Polymorphisms in the ET-1 gene (K198N), the ET receptor type A (ETA), (-231G>A and +1222C>T), and the ET type B (ETB) receptor (G57S and L277L) were genotyped. Polymorphisms were studied both individually and as haplotypes. With brain imaging, cases were subtyped into those with lacunar infarct without leukoaraiosis and those with leukoaraiosis.. No significant differences were observed between SVD cases and controls for any individual single-nucleotide polymorphism or the ETA haplotype. There were no differences between cases with isolated lacunar infarct or with lacunar infarct and leukoaraiosis.. This study, in a well-phenotyped population, does not support a role for genetic variation in the ET system as a risk factor for cerebral SVD.

Topics: Blood Vessels; Brain; Brain Infarction; Brain Ischemia; Case-Control Studies; Cerebrovascular Circulation; Endothelin-1; Endothelins; Female; Genetic Variation; Genotype; Haplotypes; Humans; Leukoaraiosis; Male; Odds Ratio; Phenotype; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptor, Endothelin A; Receptor, Endothelin B; Risk Factors; RNA, Messenger; Sequence Analysis, DNA