Zaabalawi, Azziza, Renshall, Lewis, Beards, Frances, Lightfoot, Adam P 
ORCID: 0000-0003-1501-7879, Degens, Hans, Alexander, Yvonne, Hasan, Ragheb, Bilal, Haris, Graf, Brigitte A, Harris, Lynda K et al (show 1 more authors)
(2022)
Internal Mammary Arteries as a Model to Demonstrate Restoration of the Impaired Vasodilation in Hypertension, Using Liposomal Delivery of the CYP1B1 Inhibitor, 2,3 ',4,5 '-Tetramethoxystilbene.
PHARMACEUTICS, 14 (10).
2046-.
Abstract
A significant number of patients with severe cardiovascular disease, undergoing coronary artery bypass grafting (CABG), present with hypertension. While internal mammary arteries (IMAs) may be a better alternative to vein grafts, their impaired vasodilator function affects their patency. Our objectives were to (1) determine if inhibition of the cytochrome P450 enzyme CYP1B1, using liposome-encapsulated 2,3′,4,5′-tetramethoxystilbene (TMS), can potentiate vasodilation of IMAs from CABG patients, and (2) assess mechanisms involved using coronary arteries from normal rats, in an ex vivo model of hypertension. PEGylated liposomes were synthesized and loaded with TMS (mean diameter 141 ± 0.9 nm). Liposomal delivery of TMS improved its bioavailability Compared to TMS solution (0.129 ± 0.02 ng/mL vs. 0.086 ± 0.01 ng/mL at 4 h; p < 0.05). TMS-loaded liposomes alleviated attenuated endothelial-dependent acetylcholine (ACh)-induced dilation in diseased IMAs (@ACh 10−4 M: 56.9 ± 5.1%; n = 8 vs. 12.7 ± 7.8%; n = 6; p < 0.01) for TMS-loaded liposomes vs. blank liposomes, respectively. The alleviation in dilation may be due to the potent inhibition of CYP1B1 by TMS, and subsequent reduction in reactive oxygen species (ROS) moieties and stimulation of nitric oxide synthesis. In isolated rat coronary arteries exposed to a hypertensive environment, TMS-loaded liposomes potentiated nitric oxide and endothelium-derived hyperpolarization pathways via AMPK. Our findings are promising for the future development of TMS-loaded liposomes as a promising therapeutic strategy to enhance TMS bioavailability and potentiate vasodilator function in hypertension, with relevance for early and long-term treatment of CABG patients, via the sustained and localized TMS release within IMAs.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 2,3 ',4,5 '-tetramethoxystilbene, cardiac rehabilitation, coronary artery, coronary artery bypass graft, endothelial cell, internal mammary artery, liposomes, nanoparticle drug delivery, oxidative stress, reactive oxygen species, vascular function |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 07 Feb 2023 09:43 |
| Last Modified: | 21 Mar 2023 07:55 |
| DOI: | 10.3390/pharmaceutics14102046 |
| Open Access URL: | https://doi.org/10.3390/pharmaceutics14102046 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3168234 |
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