Salusin-alpha - a New Factor in the Pathogenesis of Lipid Abnormalities in Hemodialysis Patients
Summary
Hyperlipidemia and atherosclerosis lead to cardiovascular diseases and are an indirect cause of increased death rate in the general population. This association is still more evident in specific subpopulations, like patients with advanced chronic kidney disease (CKD), especially hemodialysis (HD) patients, due to a higher prevalence of lipid disturbances and atherosclerosis compared to the general population. Cardiovascular events in CKD patients are frequently associated with traditional risk factors, including diabetes, male sex, hypertension, dyslipidemia and advanced age. However, these factors failed to fully account for the increased risk of cardiovascular events in CKD. The efforts are made to identify new risk factors that contribute to the development of atherosclerosis and participate in causes of cardiovascular death. In 2003, there were identified peptides designated salusin-alpha and salusin-beta. Development of atherosclerosis may be suppressed by salusin-alpha. Salusin-alpha may have a lipid lowering effect, similar to that of statins. The purpose of this study is to investigate whether 1) salusin-alpha is associated with lipid metabolism of HD patients (without or with metabolic syndrome or type 2 diabetes mellitus), similarly or not like in healthy or obese subjects; 2) treatment with atorvastatin and its effects are associated with changes in plasma salusin-alpha concentration, if so - whether it is dependent on the direct influence of atorvastatin on salusin-alpha or associated with a decrease in serum lipid level; 3) salusin-alpha may predict mortality in HD patients.
Timeline
- Start
- 2011-10
- Primary completion
- 2014-10
- Completion
- 2014-10
Publications
- Background Watanabe T, Sato K, Itoh F, Iso Y, Nagashima M, Hirano T, Shichiri M. The roles of salusins in atherosclerosis and related cardiovascular diseases. J Am Soc Hypertens. 2011 Sep-Oct;5(5):359-65. doi: 10.1016/j.jash.2011.06.003.
- Background Ti Y, Wang F, Wang ZH, Wang XL, Zhang W, Zhang Y, Bu PL. Associations of serum salusin-alpha levels with atherosclerosis and left ventricular diastolic dysfunction in essential hypertension. J Hum Hypertens. 2012 Oct;26(10):603-9. doi: 10.1038/jhh.2011.71. Epub 2011 Aug 11.
- Background Suzuki N, Shichiri M, Tateno T, Sato K, Hirata Y. Distinct systemic distribution of salusin-alpha and salusin-beta in the rat. Peptides. 2011 Apr;32(4):805-10. doi: 10.1016/j.peptides.2010.12.012. Epub 2010 Dec 28.
- Background Ozgen M, Koca SS, Dagli N, Balin M, Ustundag B, Isik A. Serum salusin-alpha level in rheumatoid arthritis. Regul Pept. 2011 Feb 25;167(1):125-8. doi: 10.1016/j.regpep.2010.12.003. Epub 2010 Dec 24.
- Background Nagashima M, Watanabe T, Shiraishi Y, Morita R, Terasaki M, Arita S, Hongo S, Sato K, Shichiri M, Miyazaki A, Hirano T. Chronic infusion of salusin-alpha and -beta exerts opposite effects on atherosclerotic lesion development in apolipoprotein E-deficient mice. Atherosclerosis. 2010 Sep;212(1):70-7. doi: 10.1016/j.atherosclerosis.2010.04.027. Epub 2010 May 4.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Atorvastatin | Small molecule | 10 mg | Oral |
| Comparator | Atorvastatin | Small molecule | 80 mg | Oral |