Quantification and modulation of vascular inflammatory activity for the detection and treatment of high-risk atherosclerotic plaque

Acute coronary syndrome (ACS), including myocardial infarction, is the leading cause of premature death in the UK accounting for 33,000 lost lives annually. ACS is primarily caused by rupture of high-risk/unstable plaque with subsequent thrombosis.

Despite unequivocal data establishing inflammation as a driver of plaque rupture, current imaging technologies do not provide information on arterial inflammatory activity. Myeloperoxidase (MPO) is an inflammatory enzyme expressed in high-risk human plaque.

Using a mouse model, we reported higher myeloperoxidase activity in unstable than stable plaque; molecular magnetic resonance imaging (MRI) of plaque myeloperoxidase activity using an MPO specific agent to correlate with plaque destabilization; and myeloperoxidase blockade to increase plaque stability, thereby establishing arterial myeloperoxidase activity as an imaging and therapeutic target to identify and treat high risk plaque.

We now aim to investigate whether in a rabbit model: (i)molecular MRI of myeloperoxidase activity can distinguish plaque that rupturescausing thrombosis from plaque that does not rupture;and (ii)myeloperoxidase inhibition promotes plaque stabilisation and reduces plaque rupture.

This study will answer the clinically important question whether MRI canselectively identify high-risk plaque, based on measuring disease activity, and guide treatment for reducing the risk of ACS in a precision medicine approach.