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Clinical Pharmacology & Biopharmaceutics | ISSN : 2167-065X
Volume 7
September 18-19, 2018 | Amsterdam, Netherlands
6
th
European Biopharma Congress
Euro Biopharma 2018
Inhibition of aortic calcification by policosanol in dyslipidemic rabbits is enhanced by pentoxifyllin: Potential role of
PCSK9
Mohamed M Elseweidy, Hoda E Mohamed, Rania A Elrashidy, Hebatollah H Atteia and Gehad M ELnaggar
Zagazig University, Egypt
P
olicosanol (POL) is a hypocholesterolemic drug of natural origin and has been shown to reduce circulating levels of proprotein
convertase subtilisin/kexin type 9 (PCSK9) in healthy subjects. Recently, we have reported that POL can attenuate aortic calcification
in diabetic dyslipidemic rats; however, the underlying mechanism is not fully elucidated. We aimed to investigate the effect of POL on
aortic calcification and if PCSK9 has a contributory role, and also to examine whether combination of POL with pentoxifylline (PTX), as
antitumor necrosis factor alpha (TNFα) would offer additional benefits. Thirty adult male New Zealand rabbits weighing 1.5–2 kg were
randomly assigned into five groups. One group received standard chow diet and served as normal control group (NC). The other four groups
received 0.5% w/w cholesterol rich diet for 12 weeks and concurrently treated with placebo, POL, PTX or combination of POL and PTX.
Sera samples and aortic tissue were collected for biochemical measurements and histological assessment. Rabbits fed cholesterol rich diet
demonstrated dyslipidemia, increased inflammatory state and elevated serum levels of PCSK9, compared to NC group. Aortic calcification
was evident in dyslipidemic rabbits, represented by increased calcium deposition and osteopontin (OPN) expression in aortic tissue, along
with elevated serum levels of alkaline phosphatase (ALP) and osteocalcin (OCN). Dyslipidemic rabbits showed a significant up regulation
of wingless type MMTV integration site family 3A (Wnt3a) and bone morphogenetic protein 2 (BMP 2) genes in their aortic tissue. POL
significantly reduced circulating PCSK9 levels, suppressed calcification markers and attenuated aortic calcification. Combination of POL
with PTX alleviated aortic calcification to greater extent than either monotherapy, which may be attributed to further suppression of PCSK9
and calcification markers. These findings suggested that POL exerted anti-calcifying effect partly via inhibition of PCSK9. Combination of
POL and PTX offered additional benefits and might represent a promising therapeutic option for aortic calcification.
mmElseweidy@yahoo.comClin Pharmacol Biopharm 2018, Volume:7
DOI: 10.4172/2167-065X-C1-029