Article,
Assessment of the alpha 7 nicotinic acetylcholine receptor as an imaging marker of cardiac repair-associated processes using NS14490
Affiliations
- [1] Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Scotland [NORA names: United Kingdom; Europe, Non-EU; OECD];
- [2] Kaunas Univ Technol, Dept Organ Chem, Kaunas, Lithuania [NORA names: Lithuania; Europe, EU; OECD];
- [3] Univ Edinburgh, Roslin Inst, Prote & Metabol Facil, Edinburgh, Scotland [NORA names: United Kingdom; Europe, Non-EU; OECD];
- [4] Univ Edinburgh, Roslin Inst, Prote & Metabol Facil, Edinburgh, Scotland [NORA names: United Kingdom; Europe, Non-EU; OECD];
- [5] Univ Edinburgh, Roslin Inst, Prote & Metabol Facil, Edinburgh, Scotland [NORA names: United Kingdom; Europe, Non-EU; OECD];
(... more)
Abstract
Background Cardiac repair and remodeling following myocardial infarction (MI) is a multifactorial process involving pro-reparative inflammation, angiogenesis and fibrosis. Noninvasive imaging using a radiotracer targeting these processes could be used to elucidate cardiac wound healing mechanisms. The alpha7 nicotinic acetylcholine receptor (alpha 7nAChR) stimulates pro-reparative macrophage activity and angiogenesis, making it a potential imaging biomarker in this context. We investigated this by assessing in vitro cellular expression of alpha 7nAChR, and by using a tritiated version of the PET radiotracer [F-18]NS14490 in tissue autoradiography studies.Results alpha 7nAChR expression in human monocyte-derived macrophages and vascular cells showed the highest relative expression was within macrophages, but only endothelial cells exhibited a proliferation and hypoxia-driven increase in expression. Using a mouse model of inflammatory angiogenesis following sponge implantation, specific binding of [H-3]NS14490 increased from 3.6 +/- 0.2 mu Ci/g at day 3 post-implantation to 4.9 +/- 0.2 mu Ci/g at day 7 (n = 4, P < 0.01), followed by a reduction at days 14 and 21. This peak matched the onset of vessel formation, macrophage infiltration and sponge fibrovascular encapsulation. In a rat MI model, specific binding of [H-3]NS14490 was low in sham and remote MI myocardium. Specific binding within the infarct increased from day 14 post-MI (33.8 +/- 14.1