Background: Myocardial infarction (MI) is a common and multifactorial disease. To date, causal genes and underlying mechanisms remain largely unknown. Autophagic-lysosomal system, a highly conserved degradative process in cells, has been implicated in lipid metabolism. In this study, we explored the alterations of the autophagic-lysosomal system in patients with acute MI.
Methods: Gene expression of lysosomal associated membrane protein 2 (LAMP-2), a lysosomal marker gene, and microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker gene, in the peripheral leukocytes of MI patients were examined at transcription and protein levels by RT-PCR assay and western blot analysis, respectively.
Results: Compared to age- and sex-matched healthy controls (n=146), levels of LC3 gene expression and LC3-II protein, a cleaved form of LC3 protein, were significantly decreased in MI patients (n=81). LAMP-2 gene expression and protein levels were significantly increased. Decreased LC3 gene expression (OR, 2.150, 95%CI, 1.050-4.405, P=0.036) or increased LAMP-2 gene expression (OR, 3.317, 95%CI, 1.588-6.931, P<0.001) levels were associated with MI.
Conclusions: Our findings indicated that in the peripheral leukocytes of MI patients, autophagy activity is reduced and lysosomal accumulation is increased, which may contribute to the MI pathogenesis. Further genetic analyses of autophagic-lysosomal genes are warranted.
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