Mitochondrial
DNA
Copy Number and Mitochondrial Homeostasis Genes in Acute and Stable Coronary Artery Disease
Paola Canale, Jonica Campolo, Marina Parolini, Cinzia Dellanoce, Emanuela Piccaluga, Irene Bossi, Matteo Maurina, Jacopo A. Oreglia, Rosa Sicari, Maria Grazia Andreassi ABSTRACT
Background
Mitochondrial dysfunction is increasingly implicated in coronary artery disease (CAD), but the relationship between mitochondrial DNA copy number (mtDNA‐CN) and mitochondrial homeostasis across CAD presentations remains unclear. We investigated mtDNA‐CN together with the expression of key regulators of mitochondrial biogenesis (PGC‐1α and TFAM) and mitophagy (PINK1) in patients with stable angina (SA) and acute coronary syndrome (ACS).
Methods
This observational study included 334 patients: 170 ACS, 117 SA and 47 individuals with non‐obstructive coronary arteries (NCA). Peripheral blood mtDNA‐CN and the expression of PGC‐1α, TFAM and PINK1 were quantified by real‐time PCR. Associations with clinical characteristics, inflammatory markers and left ventricular ejection fraction (LVEF) were evaluated.
Results
ACS patients exhibited significantly lower mtDNA‐CN than SA and NCA groups ( p = 0.01 and p = 0.004, respectively). PINK1 expression was reduced in both ACS ( p = 0.005) and SA ( p = 0.01) compared with NCA. TFAM expression was increased in SA ( p = 0.009), while PGC‐1α expression was higher in ACS ( p = 0.02). MtDNA‐CN and mitochondrial biomarkers were inversely associated with inflammatory markers, whereas mtDNA‐CN and TFAM correlated positively with LVEF. Lower mtDNA‐CN was independently associated with ACS (OR = 0.98, p = 0.0004) and SA (OR = 0.99, p = 0.04), while higher PINK1 expression was associated with reduced odds of SA ( p = 0.03) and ACS ( p = 0.02).
Conclusions
Mitochondrial markers are altered across CAD phenotypes. ACS is characterized by lower mtDNA‐CN and altered expression of mitochondrial homeostasis‐related genes, whereas SA shows a pattern consistent with a possible compensatory response. Combined assessment of mtDNA‐CN and mitochondrial homeostasis–related gene expression may provide a novel biomarker strategy for CAD risk stratification and targeted therapies.
Trial Registration
VICTORIA study, (