脂联素的血管及心肌保护作用

脂联素是由脂肪细胞分泌的一种内源性生物活性多肽.多项研究结果表明,脂联素具有抗炎、抗动脉粥样硬化、抑制新生血管、抗氧化应激及调节能量代谢等心血管保护作用.流行病学调查亦显示:在一些肥胖相关疾病的患者体内,脂联素水平的降低与心血管疾病风险增加相关.脂联素的作用机制复杂,与多种信号转导通路有关.脂联素有望为糖尿病心血管疾病...     

脂联素与心血管疾病的研究现状与展望

肥胖与心血管疾病及代谢紊乱密切相关。脂联素是一种脂肪源性血浆蛋白,在与肥胖相关的代谢紊乱及疾病中含量降低,低脂联素水平与肥胖相关的心血管疾病危险性增加有关。有研究表明,脂联素可直接作用于心肌及血管细胞发挥作用,可通过多种机制保护心血管系统。其中主要包括调节一磷酸腺苷活性蛋白酶介导的信号通路、抑制炎症与促进内皮细胞功能等。脂联素所共有的调节代谢、抗炎及血管保护、心肌保护作用,可为临床治疗代谢综合征性心血管疾病,提供新的干预靶点和治疗思路。     

脂联素对骨性关节炎影响的研究进展

脂联素是脂肪细胞因子中的一种。随着对脂联素研究的不断深入,已发现在多种疾病中,如心血管疾病、血管内皮功能障碍、2型糖尿病、代谢综合征和风湿性疾病,其作为炎症反应的组成部分发挥重要作用。骨性关节炎(OA)是老年人常见的关节退行性疾病,其具体病理生理机制尚不明确。本文就OA患者中脂联素的浓度,以及脂联素与脂联素受体、OA和疼痛之间的关系加以综述,以期对脂联素和OA的进一步研究提供帮助。     

脂联素与血管内皮细胞功能障碍的相关性

代谢综合征的组成成份致冠状动脉粥样硬化性心脏病发生发展的内在机制尚待进一步研究。脂联素作为一种脂肪细胞因子,与内皮依赖性血管舒张功能呈独立正相关,并且是后者的独立决定因素;通过多重信号传导途径上调内皮细胞一氧化氮合成酶活性、增加一氧化氮生成,抑制内皮细胞氧化应激反应、降低细胞损伤程度,阻断内皮细胞炎症信号传导、减轻血管炎症反应。因此,脂联素可能是联系代谢综合征与心血管疾病的枢纽,可以考虑利用脂联素改善代谢综合征患者的血管内皮功能,进而预防或延缓心血管疾病的发生发展。     

脂联素与胰岛素抵抗、动脉粥样硬化及心血管疾病

脂联素是脂肪细胞特异性细胞因子,其血浆水平与胰岛素抵抗、肥胖症、2型糖尿病以及动脉硬化疾病的发病有关。血浆脂联素在血管损伤的早期和晚期均具有终止炎症反应,阻止动脉粥样硬化发生的作用。此外,脂联素还可通过增强胰岛素的敏感性,纠正高胰岛素和高糖血症所致的高血压;通过调节代谢降低导致心血管疾病的多种危险因素。     

脂联素抑制血管紧张素Ⅱ诱导的心肌肥大的信号转导机制研究

目的 脂联素是主要由白色脂肪组织分泌的一种活性多肽,低脂联素血症与心血管疾病的发生和发展密切相关.外源性补充脂联素能够减轻压力负荷诱导的脂联素基因敲除小鼠和糖尿病小鼠出现的心肌肥大,但其具体的信号转导机制仍不十分明确.核转录因子NF-kB的活化能促进心肌细胞肥大,抑制NF-kB活性能显著减轻心肌肥大的程度.本研究探讨了球形脂联素在血管紧张素Ⅱ诱导的心肌肥大的作用及其可能的信号机制.方法 原代培养乳鼠心室肌细胞,real-time PCR和3H-亮氨酸掺入法检测心肌肥大;免疫印记法检测NF-kB核转位和腺苷酸活化蛋白激酶(AMPK)磷酸化;双荧光素酶报告基因技术检测NF-kB转录活性;EMSA检测NF-kB的DNA结合能力.结果 血管紧张素Ⅱ刺激明显增加乳鼠心肌细胞3H-亮氨酸掺入量和胎儿型基因心房钠尿肽(ANP)mRNA的表达;球形脂联素(5 mg/L)可减轻血管紧张素Ⅱ诱导的心肌细胞蛋白质合成增加和ANP mRNA表达增加,证实球形脂联素能够抑制血管紧张素Ⅱ诱导的心肌肥大.球形脂联素与心肌细胞共孵育60min能够明显抑制血管紧张素Ⅱ诱导NF-kB核转位.荧光素酶报告基因检测显示,球形脂联素抑制血管紧张素Ⅱ诱导的NF-kB转录活性增强和DNA结合活性,提示球形脂联素抑制AngⅡ诱导的心肌肥大至少部分是通过抑制NF-kB的活化实现的.球形脂联素激活心肌细胞内AMPK的磷酸化;应用AMPK的竞争性抑制剂阿糖腺苷和感染AMPK失活的腺病毒能明显削弱球形脂联素对NF-kB转位活性的抑制作用;而AMPK激动剂AICAR能够抑制血管紧张素Ⅱ诱导的NF-kB核转位增强,提示球形脂联素可以通过磷酸化AMPK抑制NF-kB活化.在抑制内源性AMPK活性后,球形脂联素抑制心肌细胞肥大的作用也被减弱.结论 球形脂联素通过磷酸化AMPK而抑制NF-kB活化,从而减轻血管紧张素Ⅱ诱导的心肌肥大.     

尿脂联素——2型糖尿病血管损害的新标志物

脂联素是脂肪细胞衍生的血管活性肽（30kDa）,通过降低血管炎症、泡沫细胞形成和细胞黏附,对血管内皮细胞产生抗炎和抗动脉粥样化作用。最近研究报道,在非糖尿病肾脏的肾小球毛细血管和肾内小动脉的内皮细胞表面有脂联素,在糖尿病肾小球毛细血管应激时,来自内皮细胞表面的脂联素被蛋白水解,由高级脂联素复合物降解为单聚体（～28kDa）、双聚体（～56kDa）和三聚体（～68kDa）而出现在尿液内,推测脂联素在尿内出现反映2型糖尿病（T2DM）肾小球血管早期损害甚于代谢改变时伴随的血脂联素变化。     

脂联素及其信号转导通路与高血压靶器官损害

高血压是一种常见而多发的心血管疾病,我国目前的高血压患者人数已超过1.6亿。高血压对机体的危害不仅是体循环的异常增高,更主要的是与之相伴的各种代谢异常及靶器官损害。血管、心脏、肾脏在高血压发展过程中将出现结构及功能的异常改变,从而又加重高血压形成恶性循环。脂联素(adiponectin)是脂肪细胞分泌的特殊蛋白质,通过调节代谢降低导致心血管疾病发生的多种危险因素,在高血压形成和发展过程中起重要作用。1脂联素及其信号转导通路与高血压1.1脂联素脂联素又叫Acrp30、AdipoQ、GBP28,是从脂肪细胞中分离出的一种结构上与补体因子C1…     

脂联素在心血管系统中的作用

脂联素是由脂肪细胞分泌的一种蛋白质,研究证实脂联素与胰岛素抵抗密切相关,具有抗动脉粥样硬化形成、抗炎症和损伤后抗内膜增生的特性。因此脂联素与糖尿病、心血管疾病密切相关,脂联素减少可作为冠心病的独立危险因子,补充脂联素可能是对上述疾病的一种新的治疗手段。     

脂联素是心血管疾病的风险预测因子?

脂联素(adiponectin)是由脂肪组织释放的一种激素,增加胰岛素敏感性和抗炎作用。体外实验显示,脂联素可影响血管内皮细胞、巨噬细胞和血管平滑肌细胞,具有抗动脉粥样硬化的作用。此外,HPFS研究(the Health Professionals Follow-up Studies)和其他的一些队列研究数据都显示,脂联素可作为心血管疾病独立的风险预测因子(主要在男性)。然而,此结论并没有得到随后的亚组研究数据的证实,包括女性群体、不同的种族、明确冠心病患者。因此,本文主要是对最近的脂联素相关研究做简要概述,内容涉及它作为风险预测因子的潜在作用及其生物学作用。     

Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis

Obesity is a risk factor for the development of many severe human diseases such as cardiovascular disorders, diabetes, and cancer, which are tightly linked to angiogenesis. The adipose tissue produces several growth factors/hormones including leptin, tumor necrosis factor alpha, and adiponectin. It has been found that adiponectin levels are reduced in obesity. Here, we report a unique function of adiponectin as a negative regulator of angiogenesis. In vitro, adiponectin potently inhibits endothelial cell proliferation and migration. In the chick chorioallantoic membrane and the mouse corneal angiogenesis assays, adiponectin remarkably prevents new blood vessel growth. Further, we demonstrate that the antiendothelial mechanisms involve activation of caspase-mediated endothelial cell apoptosis. Adiponectin induces a cascade activation of caspases-8, -9, and -3, which leads to cell death. In a mouse tumor model, adiponectin significantly inhibits primary tumor growth. Impaired tumor growth is associated with decreased neovascularization, leading to significantly increased tumor cell apoptosis. These data demonstrate induction of endothelial apoptosis as an unique mechanism of adiponectin-induced antiangiogenesis. Adiponectin, as a direct endogenous angiogenesis inhibitor, may have therapeutic implications in the treatment of angiogenesis-dependent diseases.     

脂联素对糖尿病大血管病变保护作用的研究进展

脂联素是一种脂肪细胞特异性蛋白。脂联素及其基因多态性与糖尿病大血管病变等的发生有密切的关系,脂联素通过抑制血管内皮细胞炎症及黏附、巨噬细胞向泡沫细胞转化、血管平滑肌细胞的增殖移行以及改善糖脂代谢,影响动脉粥样硬化的形成,发挥心血管保护作用。     

Adiponectin actions in the cardiovascular system

Obesity is strongly associated with the pathogenesis of type 2 diabetes, hypertension, and cardiovascular disease. Levels of the hormone adiponectin are downregulated in obese individuals, and several experimental studies show that adiponectin protects against the development of various obesity-related metabolic and cardiovascular diseases. Adiponectin exhibits favorable effects on atherogenesis, endothelial function, and vascular remodeling by modulation of signaling cascades in cells of the vasculature. More recent findings have shown that adiponectin directly affects signaling in cardiac cells and is beneficial in the setting of pathological cardiac remodeling and acute cardiac injury. Several of these effects of adiponectin have been attributed to the activation of the 5' AMP-activated protein kinase signaling cascade and other signaling proteins. This review will discuss the epidemiological and experimental studies that have elucidated the role of adiponectin in a variety of cardiovascular diseases.     

脂联素在冠状动脉粥样硬化性心脏病合并糖尿病中的研究进展

脂联素是一种具有心血管保护作用的因子。研究表明,脂联素在冠状动脉粥样硬化性心脏病的发生、发展中起保护和调控作用;冠状动脉粥样硬化性心脏病、糖尿病等疾病患者脂联素水平明显降低。     

Adiponectin: an update

The discoveries of leptin and adiponectin were breakthroughs in the field of metabolic diseases. Adipose cells produce both proteins and release them into the circulation. Leptin acts as a fundamental signal for the brain to modulate food intake as a function of energy status. Loss of leptin function results in obesity. Although a biological role for adiponectin has not been firmly established, clinical and experimental observations indicate that low plasma levels contribute to the pathogenesis of insulin resistance, type 2 diabetes and cardiovascular diseases in obese or overweight patients. Adiponectin circulates as several multimeric species, including a high-molecular-weight form thought to be the most clinically relevant. Adiponectin exerts anti-atherogenic effects by targeting vascular endothelial cells and macrophages and insulin-sensitizing effects, mainly predominantly in muscle and liver. The best-characterized molecular mechanism mediating adiponectin's metabolic and vascular activities involved stimulation of AMP kinase activity. Adiponectin signaling pathways comprise at least two putative receptors (AdipoR1 and AdipoR2). Ways to enhance adiponectin bioactivity are actively being sought. In obesity, reducing chronic adipose-tissue inflammation and macrophage infiltration into it could be beneficial to reverse downregulation of adiponectin gene expression by pro-inflammatory cytokines. Pharmacologically, thiazolidinediones and cannabinoid-1 receptor blockers (e.g., rimonabant) increase plasma adiponectin and gene expression in adipocytes. Finally, AdipoR activation to mimic adiponectin actions could prove beneficial to reduce metabolic risk factors in conditions, such as obesity, where low adiponectinemia prevails.     

Adiponectin: A multitasking player in the field of liver diseases

Adiponectin is the most abundant adipokine synthesized by adipose tissue and has been shown to be a key component in the relationship between adiposity, insulin resistance and inflammation. It circulates in plasma at physiological concentrations that represent 0.05% of all plasma proteins. Adiponectin has trimeric, hexameric and multimeric forms that bind to receptors AdipoR1, AdipoR2 and T-cadherin especially in liver, muscle and endothelial cells. Adiponectin is considered a potent modulator of lipid and glucose metabolism with antidiabetic, antiatherogenic and anti-inflammatory properties, and plays an important role in the pathogenesis of metabolic diseases. The hepatoprotective effects of adiponectin, especially in non-alcoholic fatty liver disease (NAFLD), have been widely investigated, and its antisteatotic, anti-inflammatory and antifibrogenic effects have already been described. Adiponectin levels are reduced in individuals with fatty liver disease independently of body mass index, insulin resistance and other adipokines, and are inversely related to the severity of steatosis and necroinflammation, suggesting an important role in the relationship between adipose tissue, the liver and insulin sensitivity. Adiponectin has also been found to be reduced in cases of hepatitis B and C infection, and in cholestatic and autoimmune diseases, but is increased in patients with cirrhosis of different aetiologies. In addition, an important role for the liver in the regulation of adiponectin secretion by adipocytes, mediated by bile acids, has recently been proposed. The present report describes the importance of adiponectin in hepatic diseases as well as some future perspectives of the role of adiponectin as a biomarker and therapeutic target in liver diseases.     

Adiponectin and cardiovascular disease: response to therapeutic interventions.

Adiponectin is a protein secreted specifically by adipose cells that may couple regulation of insulin sensitivity with energy metabolism and serve to link obesity with insulin resistance. Obesity-related disorders including the metabolic syndrome, diabetes, atherosclerosis, hypertension, and coronary artery disease are associated with decreased plasma levels of adiponectin, insulin resistance, and endothelial dysfunction. Adiponectin has insulin-sensitizing effects as well as antiatherogenic properties. Lifestyle modifications and some drug therapies to treat atherosclerosis, hypertension, and coronary heart disease have important effects to simultaneously increase adiponectin levels, decrease insulin resistance, and improve endothelial dysfunction. In this review, we discuss insights into the relationships between adiponectin levels, insulin resistance, and endothelial dysfunction that are derived from various therapeutic interventions. The effects of lifestyle modifications and cardiovascular drugs on adiponectin levels and insulin resistance suggest plausible mechanisms that may be important for treating atherosclerosis and coronary heart disease.