title: Statin treatment and gene expression of anti-atherogenic factor C-type natriuretic peptide system in stenotic aortic valves.
abstract: OBJECTIVE
  Aortic valve calcification is an actively regulated process with endothelial dysfunction displaying hallmarks of atherosclerosis. C-type natriuretic peptide (CNP) system has been reported to have a role in the pathogenesis of vascular atherosclerosis and to be distinctly downregulated in aortic valve stenosis (AS). Here we studied gene expressions of CNP and is target receptor natriuretic peptide receptor type B (NPR-B) in human aortic valves. Furthermore, we compared gene expression of CNP system in patients with HMG-coenzyme-A reductase (statin) treatment to non-statin-treated patients in AS group.
  
  
  RESULTS
  With the study population of 108 patients, we characterized expression of CNP and NPR-B in human aortic valves and compared normal control valves (n = 12) with valves obtained from patients with aortic regurgitation (AR, n = 16), AR with fibrosis (AR+fibr., n = 19) and AS (n = 61). By reverse transcription-polymerase chain reaction (RT-PCR), CNP mRNA levels were 89% lower (p = 0.022) in stenotic valves, when compared to AR group. Moreover, the mRNA levels of NPR-B, the target receptor of CNP, were 62% lower (p < 0.001) in stenotic valves when compared to control group and 54% lower (p = 0.002) in stenotic valves, when compared to AR group. There was no statistical significant difference in CNP and NPR-B levels in AS group when the statin-treated patients were compared to untreated patients.
  
  
  CONCLUSIONS
  These results show for the first time that the gene expression of anti-atherogenic CNP system did not differ between statin-treated and non-statin-treated patients in AS. The research data supports the results of clinical trials with the same drug class.
authors: Institution of Biomedicine, Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, Finland.
authors: Tuomas
authors: T
authors: Peltonen
authors: Pasi
authors: P
authors: Ohtonen
authors: Juha
authors: J
authors: Näpänkangas
authors: Pauli
authors: P
authors: Ohukainen
authors: Heikki
authors: H
authors: Ruskoaho
authors: Panu
authors: P
authors: Taskinen
mesh_terms: D000328:Adult; D000368:Aged; D001021:Aortic Valve / Q000473:pathology; D001024:Aortic Valve Stenosis / Q000378:metabolism*; D002114:Calcinosis / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020098:Natriuretic Peptide, C-Type / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020098:Natriuretic Peptide, C-Type; D012333:RNA, Messenger; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B