Imaging of Small Animal Peripheral Artery Disease Models: Recent Advancements and Translational Potential

Peripheral artery disease (PAD) is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead to rupture, while ischemic atherosclerosis reduces blood flow, increasing the risk of claudication, poor wound healing, limb amputation, and stroke. Current PAD treatment is often ineffective or associated with serious risks, largely because these disorders are commonly undiagnosed or misdiagnosed. Active areas of research are focused on detecting and characterizing deleterious arterial changes at early stages using non-invasive imaging strategies, such as ultrasound, as well as emerging technologies like photoacoustic imaging. Earlier disease detection and characterization could improve interventional strategies, leading to better prognosis in PAD patients. While rodents are being used to investigate PAD pathophysiology, imaging of these animal models has been underutilized. This review focuses on structural and molecular information and disease progression revealed by recent imaging efforts of aortic, cerebral, and peripheral vascular disease models in mice, rats, and rabbits. Effective translation to humans involves better understanding of underlying PAD pathophysiology to develop novel therapeutics and apply non-invasive imaging techniques in the clinic.     

Circulating YKL-40 Level,but not CHI3L1 Gene Variants,Is Associated with Atherosclerosis-Related Quantitative Traits and the Risk of Peripheral Artery Disease

YKL-40, a pleotropic cytokine, is emerging as a risk factor and a prognostic predictor of atherosclerotic cardiovascular disease. We attempted to elucidate the genetic, clinical and biochemical correlates of circulating YKL-40 level and, by combining it with CHI3L1 gene variants, with the risk and long-term mortality of peripheral artery disease (PAD). Plasma YKL-40 concentrations were measured in 612 Taiwanese individuals who had no clinically overt systemic disease. Clinical parameters, CHI3L1 gene promoter variants and 18 biomarker levels were analyzed. Eighty-six PAD patients were further enrolled for analysis. Significant associations were found between CHI3L1 genotypes/haplotypes and YKL-40 levels for the health examination subjects (smallest p = 8.36 × 10⁻⁷ for rs4950928 and smallest p = 1.72 × 10⁻¹⁰ for haplotype TGG) and also for PAD patients. For the health examination subjects, circulating YKL-40 level, but not CHI3L1 gene variants, were positively associated with age, smoking, and circulating levels of triglyceride, lipocalin 2 and multiple inflammatory biomarkers and negatively associated with low-density-lipoprotein cholesterol levels. Circulating YKL-40 level is also significantly associated with the risk of PAD (p = 3.3 × 10⁻²³). Circulating YKL40 level, but not CHI3L1 gene promoter variants, is associated with the risk of PAD in Taiwanese. The association of YKL-40 levels with multiple quantitative traits relating to the risk of PAD may provide a molecular basis linking YKL-40 to atherosclerotic cardiovascular disease.     

Association between Single Nucleotide Polymorphism rs1044925 and the Risk of Coronary Artery Disease and Ischemic Stroke

The present study was performed to clarify the association between the acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) single nucleotide polymorphism (SNP) rs1044925 and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Guangxi Han population. Polymerase chain reaction and restriction fragment length polymorphism was performed to determine the genotypes of the ACAT-1 SNP rs1044925 in 1730 unrelated subjects (CAD, 587; IS, 555; and healthy controls; 588). The genotypic and allelic frequencies of rs1044925 were significantly different between the CAD patients and controls (p = 0.015) and borderline different between the IS patients and controls (p = 0.05). The AC/CC genotypes and C allele were associated with a decreased risk of CAD and IS (CAD: p = 0.014 for AC/CC vs. AA, p = 0.022 for C vs. A; IS: p = 0.014 for AC/CC vs. AA; p = 0.017 for C vs. A). The AC/CC genotypes in the healthy controls, but not in CAD or IS patients, were associated with an increased serum high-density lipoprotein cholesterol (HDL-C) concentration. The present study shows that the C allele carriers of ACAT-1 rs1044925 were associated with an increased serum HDL-C level in the healthy controls and decreased risk in CAD and IS patients.     

Associations between Variants in IL-33/ST2 Signaling Pathway Genes and Coronary Heart Disease Risk

The IL-33/ST2 signaling pathway plays an important role in coronary artery disease (CHD); however, few studies have explored how variants in IL-33/ST2 genes influence CHD risk. Here, we examined the association between genetic variants in IL-33, ST2, and IL-1RAcP of the IL-33/ST2 axis and the risk of CHD. We conducted a case-controlled study with 1146 CHD cases and 1146 age- and sex-frequency-matched controls. Twenty-eight single nucleotide polymorphisms (SNPs) in IL-33, ST2, and IL-1RAcP were genotyped by Sequenom MassArray and TaqMan assay. Logistic regression was used to analyze these associations. The SNP rs4624606 in IL-1RAcP was nominally associated with CHD risk. The AA genotype was associated with a 1.85-fold increased risk of CHD (95% confidence interval (CI) = 1.01–3.36; p = 0.045) compared to the TT genotype. Further analysis showed that AA carriers also had a higher risk of CHD than TT + TA carriers (odds ratio (OR) = 1.85; 95% CI = 1.85–3.35; p = 0.043). However, no significant association was observed between variants in IL-33/ST2 genes and CHD risk. Further studies are needed to replicate our results in other ethnic groups with larger sample size.     

CO2在醇中溶解度的测定与分子连接性指数的关联

用恒定溶剂法测定了303.15K下CO2在乙醇、正丙醇、异丙醇、正丁醇、正戊醇、异戊醇、正己醇、正辛醇、乙二醇、1,2-丙二醇中的溶解度。实验表明:随着碳链的增长,吸收CO2的效果越好,CO2在正辛醇中的溶解度最大,CO2在二元醇中的亨利常数显著大于一元醇。利用线性回归方法建立CO2在醇中的亨利常数lgH与分子连接性指数的相关关系模型,模型计算简单易行,对CO2在醇中的亨利常数有良好的估算和预测能力,相关系数R>0.99,计算值和实验值吻合良好。研究表明:用一阶分子连接性指数1χv、羟基的个数N、经验参数COH三个参数可以描述CO2在醇中的溶解特性lgH,且精确度很高。     

Association between Phosphatase Related Gene Variants and Coronary Artery Disease: Case-Control Study and Meta-Analysis

Recent studies showed that the serum alkaline phosphatase is an independent predictor of the coronary artery disease (CAD). In this work, we aimed to summarize the association between three phosphatase related single nucleotide polymorphisms (rs12526453, rs11066301 and rs3828329) and the risk of CAD in Han Chinese. Our results showed that the rs3828329 of the ACP1 gene was closely related to the risk of CAD in Han Chinese (OR = 1.45, p = 0.0006). This significant association of rs3828329 with CAD was only found in the females (Additive model: OR = 1.80, p = 0.001; dominant model: OR = 1.69, p = 0.03; recessive model: OR = 1.96, p = 0.0008). Moreover, rs3828329 was likely to exert its effect in females aged 65 years and older (OR = 2.27, p = 0.001). Further meta-analyses showed that the rs12526453 of PHACTR11 gene (OR = 1.14, p < 0.0001, random-effect method) and the rs11066301 of PTPN11 gene (OR = 1.15, p < 0.0001, fixed-effects method) were associated with CAD risk in multiple populations. Our results showed that the polymorphisms rs12526453 and rs11066301 are significantly associated with the CAD risk in multiple populations. The rs3828329 of ACP1 gene is also a risk factor of CAD in Han Chinese females aged 65 years and older.