Regulation of Apolipoprotein a-I Gene Expression By Antihistamines

Presentation Number: MON 519
Date of Presentation: April 3rd, 2017

Ramadan Hammoud*1, Krista Lucille Gonzales1, Marilu MARGARITA Jurado2, Kui-Tzu Feng1, Luisa M. Onstead-Haas1, Norman C W Wong3, Arshag D Mooradian4 and Michael John Haas5
1University of Florida, Jacksonville, FL, 2University of Florida Jacksonville College of Medicine, Jacksonville, FL, JACKSONVILLE, 3Univ of Calgary, Calgary, AB, Canada, 4University of Florida, Jacksonville, Jacksonville, FL, 5Univ of Florida, Jacksonville, FL


Background. To identify novel compounds induce or repress hepatic apolipoprotein A-I (apo A-I) expression, we screened a library of 742 compounds composed of FDA-approved drugs and drugs in phase 2 and phase 3 clinical trials and discovered that the H1 antihistamine receptor azelastine induced hepatic apo A-I expression.

Methods. Apo A-I levels were measured by enzyme immunoassay or Western blot. Apo A-I and GAPDH mRNA levels were measured by reverse transcription real-time PCR. The effects of histamine and antihistamines on apo A-I gene transcription were determined by transient transfection of plasmids containing the apo A-I gene promoter.

Results. Azelastine treatment increased apo A-I protein and mRNA levels at 24-hours while histamine repressed apo A-I protein and mRNA levels within 48 hours in a dose-dependent manner. Azelastine and histamine increased and suppressed, respectively, apo A-I gene promoter activity through a PPARa response element. Treatment of HepG2 cells with other H1 receptor antagonists including fexofenadine, cetirizine, and diphenhydramine increased apo A-I levels in a dose-dependent manner while treatment with H2 receptor antagonists including cimetidine, famotidine, and ranitidine had no effect.

Conclusions. We conclude that antihistamines may be useful to enhance de novo apo A-1 synthesis and may be useful for treating hypoalphalipoproteinemia.


Nothing to Disclose: RH, KLG, MMJ, KTF, LMO, NCWW, ADM, MJH