Lipoprotein(a) and inflammation in human coronary atheroma: association with the severity of clinical presentation

Objectives. The purpose of this study was the investigation of the in vivo role of lipoprotein(a) [Lp(a)] and inflammatory infiltrates in the human coronary atherosclerotic plaque and their correlation with the clinical syndrome of presentation. Background. Lipoprotein(a) is an atherogenic and thrombogenic lipoprotein, and has been implicated in the pathogenesis of acute coronary syndromes. Lipoprotein(a) induces monocyte chemoattraction and smooth muscle cell activation in vitro. Macrophage infiltration is considered one of the mechanisms of plaque rupture. Methods. This study of atherectomy specimens investigated the in vivo role of Lp(a) at different stages of the atherogenic process, and its relationship with macrophage infiltration. We examined coronary atherom removed from 72 patients with stable or unstable angina. Specimens were stained with antibodies specific for Lp(a), macrophages (KP-1), and smooth muscle cells (alpha-actin). Morphometric analysis was used to quantify the plaque areas occupied by each of the three antigens, and their colocalization. Results. All specimens had localized Lp(a) staining; the mean fractional are was 58.2%. Ninety percent of the macrophage areas colocalized with Lp(a) positive areas, whereas 31.3% of the smooth muscle cell areas colocalized with Lp(a) positive areas. Patients with unstable angin (n = 46) had specimens with larger mean plaque Lp(a) areas than specimens from stable angin patients (n = 26): 64.4% versus 47.7% (p = 0.004). Unstable angin patients with rest pain (n = 28) had greater mean plaque Lp(a) are than unstable angin patients with crescendo exertional pain (n = 18): 71.1% versus 52.4% (p < 0.001). Mean KP-1 are was 31.2% in unstable rest angin versus 18.3% in stable angin (p = 0.05); alpha-actin are was greater in stable (48.5%) and crescendo exertional angin (48.8%) than in rest angin (30.4%). The strongest correlation between plaque KP-1 and Lp(a) are was in unstable rest angin (r = 0.88, p < 0.001), and between alpha-actin and Lp(a) areas in the crescendo exertional angin (r = 0.62, p < 0.01). Conclusions. Lipoprotein(a) is ubiquitous in human coronary atheroma. It is detected in larger amounts in tissue from culprit lesions in patients with unstable compared to stable syndromes, and has significant colocalization with plaque macrophages. correlation of plaque alpha-actin and Lp(a) are suggests role of Lp(a) in plaque growth.