Abstract
Activation of the classical complement pathway plays a major role in regulating atherosclerosis progression, and it is believed to have both proatherogenic and atheroprotective effects. This study focused on C1q, the first protein in the classical pathway, and examined its potentialities of plaque progression and instability and its relationship with clinical outcomes. To assess the localization and quantity of C1q expression in various stages of atherosclerosis, immunohistochemistry, western blotting, and real-time polymerase chain reaction (PCR) were performed using abdominal aortas from eight autopsy cases. C1q immunoreactivity in relation to plaque instability and clinical outcomes was also examined using directional coronary atherectomy (DCA) samples from 19 patients with acute coronary syndromes (ACS) and 18 patients with stable angina pectoris (SAP) and coronary aspirated specimens from 38 patients with acute myocardial infarction. C1q immunoreactivity was localized in the extracellular matrix, necrotic cores, macrophages and smooth muscle cells in atherosclerotic lesions. Western blotting and real-time PCR illustrated that C1q protein and mRNA expression was significantly higher in advanced lesions than in early lesions. Immunohistochemical analysis using DCA specimens revealed that C1q expression was significantly higher in ACS plaques than in SAP plaques. Finally, immunohistochemical analysis using thrombus aspiration specimens demonstrated that histopathological C1q in aspirated coronary materials could be an indicator of poor medical condition. Our results indicated that C1q is significantly involved in atherosclerosis progression and plaque instability, and it could be considered as one of the indicators of cardiovascular outcomes.
Highlights
Atherosclerosis is an inflammatory disease [1], and its associated complement activation is intimately involved in the development of multiple chronic inflammatory diseases [2, 3]
C-reactive protein (CRP) is present in the intima of atherosclerotic plaques [5, 6], and autoantibodies against oxidized low-density lipoprotein (OxLDL) [7] and heat shock proteins [8] are found in atherosclerotic lesions
Aspirated coronary materials obtained from patients with acute myocardial infarction (AMI) were investigated to evaluate whether C1q immunoreactivity in the aspirated plaque is related to clinical outcomes
Summary
Atherosclerosis is an inflammatory disease [1], and its associated complement activation is intimately involved in the development of multiple chronic inflammatory diseases [2, 3]. Some studies suggested that the complement system is activated within atherosclerotic plaques. The role of complement in atherogenesis is complicated and not fully understood, its activation has dual effects: proatherogenic and atheroprotective [4]. The classical pathway is activated mainly by immune complexes, microbial and apoptotic cells, and pattern recognition molecules such as C-reactive protein (CRP). C1q and mannose-binding lectin can trigger a rapidly enhanced phagocytosis resulting in the clearance of cellular debris, apoptotic cells, and immune complexes, which have atheroprotective effects [9]. We focused on C1q, the first protein in the classical pathway, and assessed its association with atherosclerotic lesions. We assessed C1q immunoreactivity in the culprit coronary plaques obtained by directional coronary atherectomy (DCA) and its association with acute coronary syndromes (ACS). Aspirated coronary materials obtained from patients with acute myocardial infarction (AMI) were investigated to evaluate whether C1q immunoreactivity in the aspirated plaque is related to clinical outcomes
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