Sudden coronary death in the young: Evidence of contractile phenotype of smooth muscle cells in the culprit atherosclerotic plaque.

Background: Culprit coronary atherosclerotic plaques (APs) from young sudden cardiac death (SCD) victims are mostly non-atheromatous, i.e., consisting of proliferative smooth muscle cells (SMCs). Coronary vasospasm has been advocated to explain plaque instability in the absence of thrombosis. Our aim was to characterize the SMC phenotype in the intima and media of coronary arteries from young SCD victims.

Methods And Results: A total of 38 coronary artery segments were studied: (a) 18 APs from young (≤40 years old) SCD patients, (b) 9 APs from old (>40 years old) SCD patients, (c) 11 non-atherosclerotic coronary arteries from young patients (≤40 years old). Markers of differentiated SMCs such as α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chains (SMMHCs), and heavy-caldesmon (h-CaD), were assessed in intima and media by immunohistochemistry and quantified morphometrically. In the intima, their expression was higher in non-atherosclerotic arteries (44.37 ± 3.03% for α-SMA, 14.21 ± 2.01% for SMMHCs, 8.90 ± 1.33% for h-CaD) and APs from young SCD victims (38.95 ± 2.29% for α-SMA, 11.92 ± 1.92% for SMMHCs, 8.93 ± 1.12% for h-CaD) compared with old patients (22.01 ± 3.56% for α-SMA, 6.39 ± 0.7% for SMMHCs, 3.00 ± 0.57% for h-CaD; all P statistically significant). The media of non-atherosclerotic arteries and APs from young SCD victims exhibited strong positivity for the differentiation markers unlike that of old patients.

Conclusions: SMCs of coronary APs as well as from the underlying media from young SCD victims exhibit strong contractile phenotype. In the setting of critical stenosis, both intima and media SMC contractility might contribute to transient coronary spasm leading to myocardial ischemia and SCD.