Background

Mitochondria are essential organelles present in cells and platelets, their functions ranging from energy production to metabolic regulation. They are the centre of intrinsic apoptosis pathway induced by hypoxia, oxidative stress, DNA damage and high calcium levels. Mitochondrial dysfunction is involved in diseases associated with oxidative stress, such as diabetes and atherosclerosis. In blood circulation, platelets are a major reservoir of mitochondria (averaging 4 mitochondria/platelet). They are both functional for platelet energy supply, activation and subsequent thrombosis. Mitochondrial externalization is a recognized DAMPs and impact overall vascular health and level of inflammation. This study assessed mRNA and lncRNA expression in platelets from patients with acute coronary syndrome without elevation of ST segment (NSTE) by microarray analysis.

Methods

We enrolled 9 age-matched and sex-matched consecutive patients (pts): 3 Not-diabetic pts with NSTE (NSTE), 3 Diabetic pts with NSTE (T2DM-NSTE), and 3 healthy individuals (CTRL). Platelets RNA was screened by microarray analysis.

Results

Our data suggests that mitochondrial-derived mRNAs comprise a substantial fraction of the total transcriptome. In particular, mRNAs coding for proteins involved in oxygen transport, oxidative stress response and platelet activation (ALAS, AHSP, SLC4A1, SLC25A37) were strongly upregulated in NSTE and T2DM-NSTE versus healthy group. Cell death related genes as PPP2R2B, a mayor protein phosphatase implicated in mitochondrial fission and apoptosis, is downregulated in NSTE and T2DM-NSTE groups vs CTRL. APOPT1, a mitochondrial factor promoting programmed cell death by PI3K/AKT pathway, is upregulated in T2DM-NSTE versus NSTE group.

Conclusion

Our results suggest that platelets are rich in mitochondrial RNAs. These transcripts may act as a powerful reverberator of inflammation and thrombosis. As diabetes is a pro-inflammation condition, apoptosis is strongly modulated through markedly different pathways in comparison to not diabetic setting. These study may represent a key to understand the epigenetic modulation of inflammation.