Key result
Dietary supplementation with des-fluoro-anacetrapib reduced intimal hyperplasia in grafted veins by 38% compared to control in New Zealand White rabbits.
Why the study?
Graft failure due to stenosis reduces the long-term benefit of coronary artery bypass grafting, and whether elevating HDL-C levels via CETP inhibition prevents vein bypass-induced neointimal hyperplasia remained unknown.
Does des-fluoro-anacetrapib prevent vein bypass-induced neointimal hyperplasia in New Zealand White rabbits?
Does des-fluoro-anacetrapib prevent vein bypass-induced neointimal hyperplasia in New Zealand White rabbits?
p-value: p=<0.05
Inhibiting CETP activity with des-fluoro-anacetrapib increases HDL-C levels and significantly reduces intimal hyperplasia, inflammation, and endothelial dysfunction in a rabbit model of vein bypass grafting.
CETP inhibition reduced rabbit vein graft hyperplasia; leaves open whether HDL elevation prevents clinical graft failure.
Coronary artery bypass grafting is among the most commonly performed of all cardiovascular surgical procedures. However, graft failure due to stenosis reduces the long-term benefit of the intervention. This study asks if elevating plasma high density lipoprotein cholesterol (HDL-C) levels by inhibition of cholesteryl ester transfer protein (CETP) activity with des-fluoro-anacetrapib, an analog of the CETP inhibitor anacetrapib, prevents vein bypass-induced neointimal hyperplasia. NZW rabbits were placed on a normal chow diet or chow containing 0.14% (wt/wt) des-fluoro-anacetrapib for 6 weeks. Bypass grafting of the jugular vein to the common carotid artery was performed 2 weeks after starting dietary des-fluoro-anacetrapib supplementation. The animals were euthanised 4 weeks post-bypass grafting. Relative to control, dietary supplementation with des-fluoro-anacetrapib reduced plasma CETP activity by 89 ± 6.9%, increased plasma apolipoprotein A-I levels by 24 ± 5.5%, increased plasma HDL-C levels by 93 ± 26% and reduced intimal hyperplasia in the grafted vein by 38 ± 6.2%. Des-fluoro-anacetrapib treatment was also associated with decreased bypass grafting-induced endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), endothelial dysfunction, and smooth muscle cell (SMC) proliferation in the grafted vein. In conclusion, increasing HDL-C levels by inhibiting CETP activity is associated with inhibition of intimal hyperplasia in grafted veins, reduced inflammatory responses, improved endothelial function, and decreased SMC proliferation.
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Wu et al. (2019) studied Vein bypass-induced neointimal hyperplasia (n=17). des-fluoro-anacetrapib vs. normal chow diet was evaluated on Intimal hyperplasia in the grafted vein (p=<0.05). Dietary supplementation with des-fluoro-anacetrapib reduced intimal hyperplasia in grafted veins by 38% compared to control in New Zealand White rabbits.
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