Proteomic Analysis of Circulating Monocytes Identi es Cathepsin D as A Potential Novel Plasma Marker of Acute Coronary Syndromes

We have performed a proteomic analysis of peripheral blood monocytes from ACS patients in comparison with healthy subjects and stable coronary patients in order to search novel biomarkers of ACS in circulating monocytes. Monocytes were isolated from blood of patients with non-ST elevation ACS (n = 27) at day 0, 2 and 6 months, and from patients with stable coronary disease (n = 10) and matched healthy controls (n = 11). The proteomic analysis of monocytes from ACS patients at day 0 showed that cathepsin D is differentially expressed compared to healthy subjects and stable coronary patients. Western blot analysis indicated that the mature form of cathepsin D at day 0 was overexpressed in monocytes of ACS patients in relation to healthy subjects. In contrast, the precursor of this enzyme, absent at day 0 in ACS patients, was highly expressed in monocytes of healthy subjects. Furthermore, the upregulation of the mature form of cathepsin D diminished along the time, while the expression of the precursor increased. ACS patients also showed significantly increased plasma cathepsin D levels on admission compared to healthy subjects and stable patients. Cathepsin D plasma levels diminished at 2 and 6 months to control values. Finally, cathepsin D levels were independent of the existence of coronary risk factors and CRP levels, correlating only with CD40L. Since this protease participates in the genesis and rupture of atherosclerotic plaques, it could represent a potential marker of ACS.