ABSTRACT
BACKGROUND: Cellular inhibitor of apoptosis protein 2 (cIAP2) is predicted to participate in atherosclerosis; however, its direct role in atherosclerosis development has not been investigated. We aimed to examine and assess the loss of cIAP2 on atherosclerosis lesion development. METHODS AND RESULTS: We used apoE-/- C57BL/6 male mice, either cIAP2-/- or cIAP2+/+. At 8 weeks, mice were fed a high-fat diet (HFD) for 4 and 12 weeks. Aortic root was serially sectioned and stained with Sudan IV, CD68, α-actin, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). cIAP2-/- mice displayed a significant decrease in atherosclerotic lesion's macrophage number after 4 weeks of HFD. Similarly, decrease in lesion area at 4 and 12 weeks HFD was detected by use of en face analysis (cIAP2-/- 0.58 ± 0.37% versus cIAP2+/+ 1.51 ± 0.79% [P = 0.0056]); (cIAP2-/- 9.34 ± 4.88% versus cIAP2+/+ 17.65 ± 6.24% [P = 0.0019]). Aortic root lesion area after 4 and 12 weeks of HFD also decreased (cIAP2-/- 0.0328 ± 0.014 mm2 versus cIAP2+/+ 0.0515 ± 0.021 mm2 [P = 0.022]); (cIAP2-/- 0.3614 ± 0.1157 mm2 versus cIAP2+/+ 0.4901 ± 0.125 mm2 [P = 0.065]). TUNEL analysis after 4 and 12 weeks of HFD showed a 2.5-fold increase in TUNEL+ cells (cIAP2-/- 4.47 ± 2.26% versus cIAP2+/+ 1.74 ± 0.98% [P = 0.036]); (cIAP2-/- 2.39 ± 0.75% versus cIAP2+/+ 1.29 ± 0.47% [P = 0.032]). Smooth muscle cell content in cIAP2-/- mice was 3.075 ± 3.3% compared with cIAP2+/+ with 0.085 ± 0.1% (P = 0.0071). CONCLUSIONS: Results uncover a key role for cIAP2 in atherosclerotic lesion development, and targeting it may represent a novel therapeutic strategy.
Subject(s)
Apolipoproteins E/physiology , Atherosclerosis/etiology , Diet, High-Fat , Inhibitor of Apoptosis Proteins/physiology , Animals , Apolipoproteins E/genetics , Inhibitor of Apoptosis Proteins/genetics , Male , Mice , Mice, Inbred C57BLABSTRACT
In addition to demonstrating luminal narrowings, cardiac computed tomography angiography (CTA) has the ability to detect nonstenotic plaque, vessel wall calcification and can assess left ventricular function. CTA prognostic studies have considered these components individually and in combination to produce novel risk factor scores to help predict clinical outcomes. In this article, we will consider the utility of CTA to predict clinical risk by considering the evidence for luminal stenosis, plaque scores, plaque descriptors and models combining these elements. We will also discuss some of the emerging applications of CTA that will likely provide future prognostic data in coronary artery disease patients. Although initially described as an anatomical investigation to determine the presence of coronary disease, CTA is being explored as a tool for functional imaging and may soon provide a noninvasive technique of anatomical and functional assessment previously only possible by invasive methods.
