Background: Coronary artery disease (CAD) is a common complex disease that is caused by interaction between genetic and environmental factors. Accumulating evidence indicates that foam cells in the atherosclerotic plaques exhibit the characteristics of lysosomal storage diseases, namely lysosomal accumulation of indigested materials. In patients with lysosomal storage diseases, lysosomal accumulation of lipids and cholesterols in atherosclerotic plaque cells has been observed. However, the roles of lysosomal hydrolases and proteins in the pathogenesis of atherosclerosis and CAD remain unclear.
Hypothesis: Lysosomal hydrolases and proteins may be involved in the pathogenesis of atherosclerosis and CAD by affecting lipid and cholesterol metabolism.
Methods: Expression levels of LAMP-2, a lysosomal membrane marker gene, in the peripheral leukocytes of CAD patients (n = 134) and age- and sex-matched healthy controls (n = 80) were examined at transcription and protein levels with reverse transcriptase-polymerase chain reaction and Western blot analyses, respectively. The results were compared between CAD patients and healthy controls.
Results: LAMP-2 gene expression and LAMP-2 protein levels were significantly increased in the peripheral leukocytes of CAD patients, compared with healthy controls. Furthermore, multivariate logistic regression analyses revealed that CAD is significantly associated with LAMP-2 gene expression levels (odds ratio [OR] 8.84, 95% confidence interval [CI]: 2.15-36.40, P = 0.003) or LAMP-2 protein levels (OR 2.03, 95% CI: 1.15-3.59, P = 0.015).
Conclusions: In CAD patients, LAMP-2 gene expression in the peripheral leukocytes was significantly increased than were controls, which indicates lysosomal accumulation. These data suggest that insufficient lysosomal hydrolases and proteins may lead to abnormal lipid and cholesterol metabolism, which cause initiation and progression of atherosclerosis and CAD.
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| http://dx.doi.org/10.1002/clc.20870 | DOI Listing |
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