The reduction of NDUFC2 expression is associated with mitochondrial impairment in circulating mononuclear cells of patients with acute coronary syndrome

Salvatore Raffa, Xiao Lan Diana Chin, Rosita Stanzione, Maurizio Forte, Franca Bianchi, Maria Cotugno, Simona Marchitti, Andrea Micaloni, Giovanna Gallo, Leonardo Schirone, Giuliano Tocci, Roberto Violini, Maria Rosaria Torrisi, Massimo Volpe, Speranza Rubattu

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Deficiency of NADH dehydrogenase [ubiquinone], the mitochondrial complex I, represents an emerging mechanism of cardiovascular diseases. Ndufc2, a subunit of mitochondrial complex I, is involved in stroke development. We aimed to gain some insights on the role of Ndufc2 into acute coronary syndrome (ACS) through the assessment of its gene expression, along with that of anti-oxidant proteins and of mitochondrial function parameters, in circulating mononuclear cells (PBMCs) of ACS versus stable angina (SA) patients. The impact of NDUFC2 silencing in human endothelial and vascular smooth muscle cells was assessed in vitro.

METHODS AND RESULTS: One hundred twenty-three patients presenting with SA (n = 41) or ACS (n = 82) were enrolled. PBMCs were used to assess the gene expression level of: NDUFC2, uncoupling protein 2 (UCP2), superoxide dysmutases 1 and 2 (SOD1, SOD2), levels of ROS and ATP. The mitochondrial dysfunction was assessed by cytofluorimetry; the structural damage by transmission electron microscopy. Cell viability, angiogenesis, markers of atherogenesis were evaluated in NDUFC2-silenced vascular cells. NDUFC2 mRNA level was significantly downregulated, along with UCP2, SOD1, SOD2 expression, in ACS patients. We found significant increases of ROS levels, reduced ATP levels, higher degree of mitochondrial structural damage and dysfunction in ACS patients. In vitro, NDUFC2 silencing favored mechanisms involved in atherogenesis and plaque vulnerability.

CONCLUSIONS: A significant reduction of NDUFC2 expression is detected in ACS. In vitro, NDUFC2 silencing affects vascular cell viability and angiogenesis while stimulating the expression of markers of plaque rupture. Our observations suggest that these mechanisms may contribute to ACS development.

Original languageEnglish
Pages (from-to)127-133
Number of pages7
JournalInternational Journal of Cardiology
Volume286
DOIs
Publication statusPublished - Jul 1 2019

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