Abstract 16884: Sudden Coronary Death in the Young: Evidence of a Contractile Phenotype of Smooth Muscle Cells in the Culprit Atherosclerotic Plaque
Introduction: Atherosclerotic coronary artery disease precipitating sudden cardiac death (SCD) in the young is peculiar in terms of extent (single vessel), site (left anterior descending branch) and morphology (mostly fibrocellular due to smooth muscle cells [SMC] proliferation, in the absence of thrombosis) of the culprit atherosclerotic plaque (AP).
Hypothesis: To characterize the SMCs phenotype in coronary AP from young SCD victims.
Methods: Among 652 young (< 40 years old) victims in the SCD Registry of Northeast Italy, 125 (19%) were due to coronary atherosclerosis. Fifteen AP from young atherosclerotic SCD victims with critical stenosis (>75% luminal area) and no thrombosis were selected for the study (all males, age range 17-40 years old, mean 33). AP from older (>40 years old) atherosclerotic SCD victims (n=8, 7 males) and normal coronary segments from young people (n=5, 4 males) were used for comparison. Besides traditional staining, the expression of α-smooth muscle actin (α-SMA), S100A4, smooth muscle myosin heavy chains (SMMHCs) and caldesmon (CaD) was assessed by immunohistochemistry and morphometric quantification to characterize the synthetic (α-SMA, S100A4) vs contractile (α-SMA, SMMHCs, CaD) SMC phenotype.
Results: The proportion of α-SMA positive SMCs was significantly higher in the intima of young compared to that of older SCD victims (α-SMA positive area staining/intima area: 17% vs 8% , p= 0.007). Moreover, intimal SMCs coexpressed the contractile phenotype markers SMMHCs (3.1% vs 0.6%, p=0.001) and CaD (7.1% vs 2.5%, p=0.017) in young compared to that of older SCD victims. At difference from older SCD victims, the coronary segments with AP from young SCD victims exhibited a preserved tunica media, with strong positivity for the contractile SMC markers α-SMA, SMMHCs and CaD.
Conclusions: Intimal SMCs of AP in the young exhibit a more contractile phenotype characterized by α-SMA, SMMHC and CaD expression. In the setting of critical stenosis, intimal SMC contractility and a preserved tunica media might contribute by vasospasm to transient coronary occlusion, with myocardial ischemia precipitating SCD.
Author Disclosures: S. Rizzo: None. M. Coen: None. A. Sakic: None. G. Thiene: None. G. Gabbiani: None. C. Basso: None. M. Bochaton-Piallat: None.
- © 2016 by American Heart Association, Inc.