APOLIPOPROTEIN CELLULAR INTERACTIONS IN VASCULAR BIOLOGY

低脂HDL载脂蛋白的相互作用，通过由ABC转运蛋白ABC 1控制的活性高尔基体依赖性途径刺激细胞分泌过量胆固醇。该途径产生含有脂质和细胞囊泡转运蛋白（如betaCOP）的颗粒，并且似乎依赖于细胞蛋白聚糖。分泌的含β-COP的颗粒与结合肝素的血浆HDL的底物结合。因此，贫脂载脂蛋白通过复杂的分泌途径去除细胞脂质和蛋白质，该途径产生可瞬时结合动脉基质蛋白聚糖的颗粒。我们的假设是载脂蛋白与动脉细胞的相互作用通过多种机制保护动脉粥样硬化，包括去除多余的细胞胆固醇和产生干扰致动脉粥样硬化脂蛋白与动脉蛋白聚糖结合的颗粒。我们将定义成纤维细胞，培养的动脉平滑肌细胞和巨噬细胞中的载脂蛋白介导的分泌途径的生物化学和形态学特性，我们将表征在这些不同的细胞中调节这一途径的因素。我们还将进行研究，以确定和表征在这些不同细胞中调节这一途径的细胞蛋白和蛋白聚糖。我们还将进行研究，以确定和表征细胞蛋白质和蛋白聚糖的调节。响应于细胞载脂蛋白相互作用而转运和/或分泌。最后，我们将表征分泌的和血浆中含β COP颗粒与蛋白聚糖的结合，并鉴定含β COP颗粒中的肝素和蛋白聚糖结合蛋白。这些研究将更详细地定义动脉壁细胞中载脂蛋白介导的分泌途径的性质，并提供更多的了解该途径保护动脉粥样硬化的机制。对HDL载脂蛋白抗动脉粥样硬化作用的细胞和细胞外机制的理解可能提示HDL载脂蛋白抗动脉粥样硬化作用的细胞外机制可能提示预防和消退心血管疾病的治疗干预。

The interaction of lipid-poor HDL apolipoproteins which cells stimulates secretion of excess cholesterol by an active Golgi-dependent pathway controlled by an ABC transporter called ABC1. This pathway generates particles containing lipids and cellular vesicular transport proteins such as betaCOP and appears to depend on cellular proteoglycans. The secreted betaCOP-containing particles become associated with a subst of plasma HDL that binds heparin. Thus, lipid-poor apolipoproteins remove cellular lipids and proteins by a complex secretory pathway that generates particles that may transiently bind to arterial matrix proteoglycans. Our hypothesis is that the interaction of apolipoproteins with arterial cells protects against atherosclerosis by multiple mechanisms, including removing excess cellular cholesterol and producing particles that interfere with binding of atherogenic lipoproteins to arterial proteoglycans. We will define the biochemical and morphological properties of the apolipoprotein-mediated secretory pathway in fibroblast, cultured arterial smooth muscle cells, and macrophages, and we will characterize factors that regulate this pathway in these different cells. We will also conduct studies to identify and characterize cellular proteins and proteoglycans that regulate this pathway in these different cells. We will also conduct studies to identify and characterize cellular proteins and proteoglycans that are regulated., transported, and/or secreted in response to cellular apolipoprotein interactions. Lastly, we will characterize the binding of secreted and plasma betaCOP-containing particles to proteoglycans and identify the heparin and proteoglycan binding protein(s) in betaCOP- containing particles. These studies will define in more detail the properties of the apolipoprotein-mediated secretory pathway in arterial wall cells and provide more insight into mechanisms by which this pathway protects against atherosclerotic. An understanding of the cellular and extracellular mechanisms that underlie the anti-atherogenic effects of HDL apolipoproteins may suggest extracellular mechanisms that underlie the anti-atherogenic effects of HDL apolipoproteins may suggest therapeutic interventions for preventing and regressing cardiovascular disease.