Anti-atherosclerosis effect of different doses of CETP vaccine in rabbit model of atherosclerosis.
OBJECTIVE
To evaluate atheroprotective effects of different doses of cholesteryl ester transfer protein (CETP) vaccine, three doses of Tetanus toxoid-CETP (TT-CETP) peptide including 10, 50 and 100/rabbit, termed FA10, FA50, FA100, respectively, were administered in rabbit model of atherosclerosis.


METHODS
Animals were vaccinated subcutaneously (S.C.) with 100μl of vaccine in presence of complete Freund's adjuvant (CFA) for the first administration. Rabbits were boosted 4 times at 3 weeks intervals with the same peptide dose formulated in incomplete Freund's adjuvant (IFA). Animals were fed with diet supplemented with 2% cholesterol from week 11 to week 19. Anti-TT-CETP specific antibody and CETP activity in sera were determined. Therapeutic response was examined by tracking plasma lipoprotein levels (HDL-C, LDL-C and total cholesterol), and pathologic observation of intima/media thickness at the site of aortic lesions.


RESULTS
All TT-CETP vaccine doses generated strong anti TT-CETP antibody response. CETP activity reduced in rabbits vaccinated with FA100 (P=0.031). FA100 showed significant increase in level of HDL-C rather than control group (P=0.006). However, no significant reduction were found in atherosclerotic lesion when compared to control.


CONCLUSIONS
Inhibition of CETP activity and increased HDL-C were found with FA100, but the vaccine failed to prevent aortic lesion development in immunized rabbits when compared to control. Our result supports the hypothesis stated that CETP may not be an attractive therapeutic target for the prevention of cardiovascular disease.
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran.
Tamara
T
Aghebati
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran.
Ali
A
Badiee
Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Amir Hooshang
AH
Mohammadpour
Department of Anatomy, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran; Medical Toxicology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran.
Mohammad
M
Afshar
Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran.
Mahmoud Reza
MR
Jaafari
Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Khalil
K
Abnous
Department of Cardiovascular Diseases, Razavi Hospital, 9148857114 Mashhad, Iran.
Sobhan
S
Issazadeh
Razavi Hospital, Mashhad, Iran.
Saeed
S
Hashemzadeh
17 Shahrivar Hospital, Mashhad, Iran.
Mohammad
M
Zareh
Department of Nursing, Quchan Branch, Islamic Azad University, Quchan, Iran.
Haydeh
H
Hashemizadeh
Department of Cardiovascular Diseases, Razavi Hospital, 9148857114 Mashhad, Iran. Electronic address: Saeednazemi@gmail.com.
Saeed
S
Nazemi
D000818:Animals; D000906:Antibodies / Q000097:blood; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology*; D053480:Cholesterol Ester Transfer Proteins / Q000008:administration & dosage* / Q000276:immunology*; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D008074:Lipoproteins / Q000378:metabolism; D011817:Rabbits; D015430:Weight Gain
D000906:Antibodies; D053480:Cholesterol Ester Transfer Proteins; D008074:Lipoproteins
Atherosclerosis; CETP vaccine; Cardiovascular disease; HDL-C