{Reference Type}: Journal Article
{Title}: Expression of ectopic trypsin in atherosclerotic plaques and the effects of aprotinin on plaque stability.
{Author}: Shi JY;Pan HY;Liu K;Pan M;Si GJ;
{Journal}: Arch Biochem Biophys
{Volume}: 690
{Issue}: 0
{Year}: 09 2020 15
{Factor}: 4.114
{DOI}: 10.1016/j.abb.2020.108460
{Abstract}: Our previous research revealed that trypsin is abundantly expressed in atherosclerotic plaques and its distribution overlaps with that of matrix metalloproteinase-9 (MMP-9). This study was performed to explore the possible roles of trypsin in vulnerable atherosclerotic plaque formation.<BR>Twenty-four rabbits were randomly assigned to a normal (control) group, an atherosclerosis (experimental) group and a trypsin inhibitor (aprotinin) group. In the 13th feeding week, the aprotinin group was treated with 5 mg/kg/day aprotinin via ear vein for 4 weeks. At the end of the 16th week, coronary arterial and aortic expression of trypsin, proteinase-activated receptor-2 (PAR-2), activated MMP-9, and pro-inflammatory cytokines were significantly greater in the experimental group than in the control group. Aprotinin decreased trypsin expression and activation in plaques, blocked PAR-2 and MMP-9 activation, and decreased cytokine expression; it also increased fibrous cap thickness, decreased the intima-media thickness and intimal/medial ratio, thus significantly ameliorating plaque vulnerability. Upregulated trypsin, MMP-9 and PAR-2 were also found in coronary intimal atherosclerotic plaques of patients undergoing coronary artery bypass grafting.<BR>Ectopic trypsin was significantly upregulated in atherosclerotic plaques, which increased pro-inflammatory cytokine levels by activating PAR-2 and promoted plaque instability by activating proMMP-9, thereby promoting atherosclerosis and plaque vulnerability. In addition, the high trypsin expression in human coronary intimal atherosclerotic plaques suggests that targeting trypsin may be a new strategy for acute coronary syndrome prevention.