Effects of rosuvastatin on 3-nitrotyrosine and aortic stiffness in hypercholesterolemia.
OBJECTIVE
Early atherosclerosis is characterized by reduced large artery distensibility, paralleled by an increased peroxynitrite formation and nitration of tyrosine in proteins. The aim of the present study was to investigate the short-term effect of cholesterol lowering with rosuvastatin on 3-nitrotyrosine (3-NT), a marker of peroxynitrite-mediated oxidative stress, and on arterial stiffness.


RESULTS
71 outpatients with primary hypercholesterolemia were recruited for this randomized open-label intervention study; 35 patients were assigned to 4-week rosuvastatin therapy (10mg daily) with a low-fat diet, and 36 patients to a low-fat diet only. Within the cohort of 71 hypercholesterolemic patients, there was a significant correlation between cholesterol levels, 3-NT and aortic pulse wave velocity (aPWV), that is a reliable measure of aortic stiffness. Among those patients who received rosuvastatin, significant reductions in plasma cholesterol, 3-NT and aPWV were observed. Reductions in both aPWV and 3-NT levels correlated significantly with the decrease in plasma cholesterol. Reduction of plasma cholesterol was the only independent predictor for reduced arterial stiffness following rosuvastatin therapy.


CONCLUSIONS
Cholesterol reduction achieved following short-term rosuvastatin therapy is associated with a decrease in peroxynitrite-mediated oxidative stress and an improvement in large artery distensibility; reduction in arterial stiffness is directly attributable to rosuvastatin-induced cholesterol lowering and not to reduction of plasma 3-NT levels.
Pirro
Matteo
M
Unit of Internal Medicine, Department of Clinical and Experimental Medicine, University of Perugia, Ospedale R. Silvestrini, S. Andrea delle Fratte, 06100 Perugia, Italy.
Schillaci
Giuseppe
G
Mannarino
Massimo Raffaele
MR
Savarese
Gianluca
G
Vaudo
Gaetano
G
Siepi
Donatella
D
Paltriccia
Rita
R
Mannarino
Elmo
E
D000328:Adult; D000368:Aged; D001011:Aorta / Q000187:drug effects* / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D003131:Combined Modality Therapy; D003187:Compliance; D018752:Diet, Fat-Restricted; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011673:Pulsatile Flow; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C002744:3-nitrotyrosine; D014443:Tyrosine; D000068718:Rosuvastatin Calcium; D002784:Cholesterol