Involvement of enhanced expression of classical complement C1q in atherosclerosis progression and plaque instability: C1q as an indicator of clinical outcome

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.

Identification and Validation of Candidate Gene Module Along With Immune Cells Infiltration Patterns in Atherosclerosis Progression to Plaque Rupture via Transcriptome Analysis

“…The classical complement C1q, mainly produced by macrophages in vivo (53), can promote macrophage survival during ingestion of excess cholesterol and improves foam cell efferocytosis function, which provides insight into the protective role of C1q in early atherosclerosis (54,55). However, C1q was recently reported to be positively associated with coronary artery disease and could be considered as one of the indicators of cardiovascular outcomes (56,57), and this was also reflected in our study that enhanced expression of C1q (C1QC and C1QA) may be a contributory factor to instability or rupture of atherosclerotic plaques. Additionally, previously published results suggested a strong association between hemoglobinhaptoglobin scavenger receptor CD163 expression in alternative macrophages and atherosclerotic disease progression, leading to intimal angiogenesis, promoted vascular permeability, and plaque inflammation (58,59).…”

The clinical role of combined circulating complement C1q and AIP for CAD with LDL-C level below 1.8mmol/L

“…Research has indicated that the comparative levels of protein and mRNA expression of C1q exhibited a noteworthy increase in advanced atherosclerotic plaques compared with early lesions. Furthermore, the expression of C1q in the culprit plaques of patients diagnosed with ACS significantly surpassed that in patients with stable angina pectoris [ 14 ]. In recent clinical studies involving C1q, the serum complement C1q was significantly correlated with cardiovascular outcomes in ACS patients undergoing PCI treatment when levels of the highly-sensitive CRP (hs-CRP) were below 2 mg/L.…”

An integrative analysis of single-cell and bulk transcriptome and bidirectional mendelian randomization analysis identified C1Q as a novel stimulated risk gene for Atherosclerosis

“…Previous research has indicated a positive correlation between C1Q and coronary artery disease, with the potential for it to serve as a cardiovascular event indicator ( 61 , 62 ). Our own investigation supports this finding, as heightened C1Q expression may significantly contribute to atherosclerotic plaque instability or rupture.…”