No abstract

Background-The endoplasmic reticulum (ER) responds to various stresses by upregulation of ER chaperones, but prolonged ER stress eventually causes apoptosis. Although apoptosis is considered to be essential for the progression and rupture of atherosclerotic plaques, the influence of ER stress and apoptosis on rupture of unstable coronary plaques remains unclear. Methods and Results-Coronary artery segments were obtained at autopsy from 71 patients, and atherectomy specimens were obtained from 40 patients. Smooth muscle cells and macrophages in the fibrous caps of thin-cap atheroma and ruptured plaques, but not in the fibrous caps of thick-cap atheroma and fibrous plaques, showed a marked increase of ER chaperone expression and apoptotic cells. ER chaperones also showed higher expression in atherectomy specimens from patients with unstable angina pectoris than in specimens from those with stable angina. Expression of 7-ketocholesterol was increased in the fibrous caps of thin-cap atheroma compared with thick-cap atheroma. Treatment of cultured coronary artery smooth muscle cells or THP-1 cells with 7-ketocholesterol induced upregulation of ER chaperones and apoptosis, whereas these changes were prevented by antioxidants. We also investigated possible signaling pathways for ER-initiated apoptosis and found that the CHOP (a transcription factor induced by ER stress)-dependent pathway was activated in unstable plaques. In addition, knockdown of CHOP expression by small interfering RNA decreased ER stress-dependent death of cultured coronary artery smooth muscle cells and THP-1 cells. Conclusions-Increased ER stress occurs in unstable plaques. Our findings suggest that ER stress-induced apoptosis of smooth muscle cells and macrophages may contribute to plaque vulnerability.

Six months of DAPT was not inferior to 18 months of DAPT following implantation of a DES with a biodegradable abluminal coating. However, this result needs to be interpreted with caution given the open-label design and wide noninferiority margin of the present study. (Nobori Dual Antiplatelet Therapy as Appropriate Duration [NIPPON]; NCT01514227).

BackgroundCardiovascular cine magnetic resonance (CMR) accelerated by compressed sensing (CS) is used to assess left ventricular (LV) function. However, it is difficult for prospective CS cine CMR to capture the complete end-diastolic phase, which can lead to underestimation of the end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF), compared to retrospective standard cine CMR. This prospective study aimed to evaluate the diagnostic quality and accuracy of single-breath-hold full cardiac cycle CS cine CMR, acquired over two heart beats, to quantify LV volume in comparison to multi-breath-hold standard cine CMR.MethodsEighty-one participants underwent standard segmented breath-hold cine and CS real-time cine CMR examinations to obtain a stack of eight contiguous short-axis images with same high spatial (1.7 × 1.7 mm2) and temporal resolution (41 ms). Two radiologists independently performed qualitative analysis of image quality (score, 1 [i.e., “nondiagnostic”] to 5 [i.e., “excellent”]) and quantitative analysis of the LV volume measurements.ResultsThe total examination time was 113 ± 7 s for standard cine CMR and 24 ± 4 s for CS cine CMR (p < 0.0001). The CS cine image quality was slightly lower than standard cine (4.8 ± 0.5 for standard vs. 4.4 ± 0.5 for CS; p < 0.0001). However, all image quality scores for CS cine were above 4 (i.e., good). No significant differences existed between standard and CS cine MR for all quantitative LV measurements. The mean differences with 95 % confidence interval (CI), based on Bland–Altman analysis, were 1.3 mL (95 % CI, −14.6 – 17.2) for LV end-diastolic volume, 0.2 mL (95 % CI, −9.8 to10.3) for LV end-systolic volume, 1.1 mL (95 % CI, −10.5 to 12.7) for LV stroke volume, 1.0 g (95 % CI, −11.2 to 13.3) for LV mass, and 0.4 % (95 % CI, −4.8 – 5.6) for LV ejection fraction. The interobserver and intraobserver variability for CS cine MR ranged from −4.8 – 1.6 % and from −7.3 – 9.3 %, respectively, with slopes of the regressions ranging 0.88–1.0 and 0.86–1.03, respectively.ConclusionsSingle-breath-hold full cardiac cycle CS real-time cine CMR could evaluate LV volume with excellent accuracy. It may replace multi-breath-hold standard cine CMR.