A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs

Fatty acids, which are essential nutritional components, are also involved in cardiovascular and metabolic diseases. Here we report a human cell surface receptor that we name free fatty acid receptor (FFAR), because it is specifically activated by medium to long-chain free fatty acids. The receptor belongs to the class of seven-transmembrane, G-protein coupled receptors (GPCRs) and also mediates responses to antidiabetic drugs of the thiazolidinedione type. It is expressed in skeletal muscle, heart, liver, and pancreatic beta-cells. Stimulation of FFAR increases the intracellular calcium concentration in cells expressing the receptor in a native (pancreatic beta-cell line) or in a recombinant form. In view of the nature of the activating substances, their physiological role in the body, and the tissue distribution of FFAR we suggest the term "nutrient sensing receptor" for receptors acting at the interface between dietary components and signalling molecules.     

Moderate Accumulation of Calcium and Phosphorus in the Splenic Artery with Aging and Low Accumulation of Those in the Pulmonary Artery with Aging

To elucidate compositional changes of the arteries with aging, the authors investigated age-related changes of elements in the splenic and pulmonary arteries, which supplied blood to contractile organs. After ordinary dissection by medical students at Nara Medical University was finished, the splenic and pulmonary arteries were resected from the subjects, ranging in age from 58 to 94 years. The element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that a moderate accumulation of Ca and P occurred in the splenic artery with aging, but it hardly occurred in the pulmonary artery with aging. Regarding the relationship among elements, the finding that there were significant direct correlations among the contents of Ca, P, Mg, and Na was commonly obtained in both the splenic and pulmonary arteries. The accumulation of Ca and P in the splenic artery with aging occurred independently of that in the pulmonary artery. Histologic observation indicated that a major part of Ca deposits was seen in the middle tunica, but not in the internal tunica. Therefore, the calcification occurring in the splenic artery belonged to middle sclerosis.     

腔内治疗下肢动脉硬化闭塞症的临床研究

目的：下肢动脉硬化闭塞症（arteriosclerosis obliterans,ASO）是血管外科常见疾病,我们拟讨论腔内成形术在ASO治疗中的应用。方法：回顾2008年5月至2010年4月我科收治的76例ASO病例,对手术成功率、手术效果和糖尿病等合并症对疗效的影响进行分析。结果：总体技术成功61例,技术成功率80.3%,Fontaine II期组技术成功36例（成功率92.3%）,明显高于III期（82.1%）和IV期组（22.2%）;合并糖尿病组22例（28.9%）,技术成功15例（成功率68.2%）,低于无糖尿病组的85.2%;结论：腔内成形术是治疗ASO的有效微创手术方法,积极腔内手术干预有助提高早期患者成功率,同时对晚期患者可有效改善症状。     

腔内治疗下肢动脉硬化闭塞症的临床研究

目的:下肢动脉硬化闭塞症(arteriosclerosis obliterans,ASO)是血管外科常见疾病,我们拟讨论腔内成形术在ASO治疗中的应用.方法:回顾2008年5月至2010年4月我科收治的76例ASO病例,对手术成功率、手术效果和糖尿病等合并症对疗效的影响进行分析.结果:总体技术成功61例,技术成功率80.3%,FontaineⅡ期组技术成功36例(成功率92.3%),明显高于Ⅲ期(82.1%)和Ⅳ期组(22.2%);合并糖尿病组22例(28.9%),技术成功15例(成功率68.2%),低于无糖尿病组的85.2%;结论:腔内成形术是治疗ASO的有效微创手术方法,积极腔内手术干预有助提高早期患者成功率,同时对晚期患者可有效改善症状.     

Colocalization of oxidized low-density lipoprotein, caspase-3, cyclooxygenase-2, and macrophage migration inhibitory factor in arteriosclerotic human carotid arteries

Apoptotic and inflammatory processes occur in human arteriosclerotic lesions. We examined the hypothesis whether both processes are possibly associated by studying the colocalization of corresponding markers. In 11 human arteriosclerotic carotid arteries, proapoptotic markers (CPP32 (caspase-3), poly(ADP-ribose) polymerase, apoptosis-inducing factor, c-Jun/AP-1, and p53) and proinflammatory markers (macrophage migration inhibitory factor (MIF) and cyclooxygenase-2) were found in macrophages (MΦ) evaluated by computer-assisted immunohistomorphometry. Double-labeling studies demonstrated a colocalization of, both, proapoptotic and proinflammatory markers in these MΦ. Moreover, these MΦ also contained oxidized low-density lipoproteins (oxLDL). Exposure of cultured human MΦ to oxLDL, C₆-ceramide, and tumor necrosis factor-alpha or H₂O₂ resulted in a significant increase of the apoptosis rate as well as of the MIF protein expression. Our study of MΦ in arteriosclerotic carotid arteries and in vitro experiments provide evidence that markers of apoptosis and inflammation are not only significantly increased but are also coexpressed. We conclude there are reciprocal modulatory interactions between apoptotic and inflammatory pathways in human plaque MΦ, which might importantly modify plaque progression or stability. J. Metz and R. Kinscherf are senior authors.     

2型糖尿病合并下肢动脉粥样硬化的危险因素

下肢动脉粥样硬化是2型糖尿病(T2DM)患者最常见的大血管并发症之一。作为T2DM患者严重的慢并发症之一,下肢动脉粥样硬化可引起糖尿病足的发生,严重情况下可导致足坏疽。因此,阐明T2DM合并下肢动脉粥样硬化的危险因素,早期预防和治疗糖尿病合并下肢动脉粥样硬化症,不仅提高了患者的生活质量,而且减轻了家庭和社会的经济负担,具有较大的现实意义。影响T2DM患者下肢动脉粥样硬化的因素错综复杂,分为不可调控的和可调控的因素,不可调控的危险因素包括年龄、种族、遗传等,可调控的危险因素包括吸烟、高血糖、高血脂、高血压,以及近年提出的肥胖、胰岛素抵抗、高纤维蛋白血症、炎症等。本文就T2DM合并下肢动脉粥样硬化的危险因素做一综述。     

Whole-exome sequencing reveals damaging gene variants associated with hypoalphalipoproteinemia

Low levels of high density lipoprotein-cholesterol (HDL-C) are associated with an elevated risk of arteriosclerotic coronary heart disease. Heritability of HDL-C levels is high. In this research discovery study, we used whole-exome sequencing to identify damaging gene variants that may play significant roles in determining HDL-C levels. We studied 204 individuals with a mean HDL-C level of 27.8 ± 6.4 mg/dl (range: 4–36 mg/dl). Data were analyzed by statistical gene burden testing and by filtering against candidate gene lists. We found 120 occurrences of probably damaging variants (116 heterozygous; four homozygous) among 45 of 104 recognized HDL candidate genes. Those with the highest prevalence of damaging variants were ABCA1 (n = 20), STAB1 (n = 9), OSBPL1A (n = 8), CPS1 (n = 8), CD36 (n = 7), LRP1 (n = 6), ABCA8 (n = 6), GOT2 (n = 5), AMPD3 (n = 5), WWOX (n = 4), and IRS1 (n = 4). Binomial analysis for damaging missense or loss-of-function variants identified the ABCA1 and LDLR genes at genome-wide significance. In conclusion, whole-exome sequencing of individuals with low HDL-C showed the burden of damaging rare variants in the ABCA1 and LDLR genes is particularly high and revealed numerous occurrences in HDL candidate genes, including many genes identified in genome-wide association study reports. Many of these genes are involved in cancer biology, which accords with epidemiologic findings of the association of HDL deficiency with increased risk of cancer, thus presenting a new area of interest in HDL genomics.     

Histological changes in the penis of the Chacma baboon--a model to study aging penile vascular impotence

Light and scanning electron microscopy was performed on the penes of Chacma baboons to establish their suitability as animal model for studying vascular impotence. Analogous aging penile vascular changes were found in man, and a fibrous trabeculopathy with intertrabecular senechiae was demonstrated. Considering the corresponding changes, the Chacma baboon could thus be regarded suitable for studying the pathophysiology of aging penile vascular changes.     

玉米胚芽降血脂作用的研究

玉米胚芽经提取精制得到粉状物(YF)。以含15％YF的饲料饲喂大、小鼠,可在短期内阻抑实验性高血脂大、小鼠血清总胆固醇(TC)的升高(P<0.01),并显著升高小鼠高密度脂蛋白胆固醇(HDL-C)含量(P<0.01),使TC-HDL-c/HDL-c显著降低(P<0.01)。对高血脂患者食用YF2个月的食疗观察表明,YF的降脂效果与动物实验一致,并且能使血浆卵磷脂酰基转移酶(LCAT)相对活性升高(P<0.05)。提示YF可能具有促进体内游离胆固醇(FC)转化为酯化胆固醇(EC),从而加速胆固醇从肝内移出的作用,对此尚需进一步研究。     

NLRP3炎性小体及其下游产物在TAO和ASO患者动脉中的表达及意义

目的:探讨NLRP3炎性小体及其下游产物在血栓闭塞性脉管炎(TAO)和动脉粥样硬化闭塞症(ASO)患者动脉中的表达及意义。方法:选择8例TAO患者截肢后的下肢动脉,13例ASO患者截肢后的下肢动脉,5例因窒息死亡的新生儿主动脉,将三组动脉分别进行HE染色及免疫组化分析,半定量的测量3组动脉中NLRP3、Caspase-1、IL-1β和IL-18的累积光密度值(IOD)并进行组间比较。结果:3组动脉组织的HE染色结果均符合其特征。TAO组和ASO组动脉组织中NLRP3、Caspase-1、IL-1β和IL-18的表达与对照组相比均显著升高,差异具有统计学意义(P0.05)。结论:NLRP3、Caspase-1、IL-1β和IL-18在TAO和ASO患者动脉组织中的表达明显升高,NLRP3炎性小体及其下游产物可能参与了TAO和ASO的发病过程。