Nitric oxide regulation of protein trafficking in the cardiovascular system

Nitric oxide (NO) is a second messenger with diverse roles in the cardiovascular system, such as inhibiting thrombosis and limiting vascular inflammation. One mechanism by which NO modulates such disparate physiological processes is by regulating protein trafficking within cells. NO inhibits exocytosis of endothelial granules which would otherwise trigger inflammation. NO also blocks platelet secretion of granules that would otherwise activate thrombosis. NO decreases granule trafficking from the Golgi to the plasma membrane by targeting a key component of the exocytic machinery, N-ethylmaleimide sensitive factor (NSF). In contrast to its inhibitory effects on exocytosis, NO accelerates endocytosis. S-nitrosylation of dynamin increases its ability to hydrolyze GTP, assemble in oligomers around a nascent vesicle, and cleave the endocytic vesicle free from the plasma membrane. NO regulation of vesicle trafficking is a molecular mechanism that explains some of the cardiovascular effects of NO, and may be of broad physiological significance.     

Growth factor signal transduction defects in the cardiovascular system

Growth factors are important molecules mediating both the development as well as adaptive and pathological changes within the cardiovascular system. Growth factors therefore mediate both beneficial and nonbeneficial effects. The beneficial actions include the improvement of endothelial function, stimulation of vascular repair, the formation of new capillaries (angiogenesis), and the growth of collateral arteries (arteriogenesis). These actions represent the conceptual basis for the therapeutic use of growth factors, based on the idea to therapeutically induce or accelerate a given beneficial process. The beneficial effects of growth factors have to be separated from effects where growth factors act as mediators of pathological processes such as atherogenesis and plaque destabilization. This review article focuses on the physiological and beneficial effects of growth factors in the vessel wall and describes and explains the dysfunction of these effects under certain conditions now referred to as "growth factor signal transduction defects".     

转录因子FoxO1的修饰调节效应及在心血管疾病中的作用

FoxO1是FoxO亚家族中最早发现的转录因子,其转录活性受到多种蛋白修饰的调节。近年研究显示,FoxO1在多种心血管疾病的发生、发展中都发挥着重要作用。本文在此对FoxO1的修饰调节效应及其在心血管疾病中的作用作一综述。     

肝纤维化中转录因子的调控作用

肝纤维化是继发于各种形式的慢性肝损伤之后的组织修复过程中的代偿反应,他也是慢性肝病发展为肝硬化的必经病理过程.各种病因所引起的慢性肝病绝大多数都有肝纤维化,其中25%-40%最终发展为肝硬化乃至肝癌.因此,肝纤维化的发生机制成为目前慢性肝病的研究热点之一.肝纤维化的形成是一个多因素、多细胞参与的复杂过程,涉及多种细胞因子和蛋白成分表达的改变,而基因转录水平的调控可能在影响其表达中起到了关键作用.现就几种重要的转录因子在肝纤维化发生、发展过程中的可能调控作用作一综述.     

Beta 3-adrenoreceptor regulation of nitric oxide in the cardiovascular system

The presence of a third β-adrenergic receptor (β3-AR) in the cardiovascular system has challenged the classical paradigm of sympathetic regulation by β1- and β2-adrenergic receptors. While β3-AR's role in the cardiovascular system remains controversial, increasing evidence suggests that it serves as a “brake” in sympathetic overstimulation — it is activated at high catecholamine concentrations, producing a negative inotropic effect that antagonizes β1- and β2-AR activity. The anti-adrenergic effects induced by β3-AR were initially linked to nitric oxide (NO) release via endothelial NO synthase (eNOS), although more recently it has been shown under some conditions to increase NO production in the cardiovascular system via the other two NOS isoforms, namely inducible NOS (iNOS) and neuronal NOS (nNOS). We summarize recent findings regarding β3-AR effects on the cardiovascular system and explore its prospective as a therapeutic target, particularly focusing on its emerging role as an important mediator of NO signaling in the pathogenesis of cardiovascular disorders.     

Homeobox protein Hop functions in the adult cardiac conduction system

Hop is an unusual homeobox gene expressed in the embryonic and adult heart. Hop acts downstream of Nkx2-5 during development, and Nkx2-5 mutations are associated with cardiac conduction system (CCS) defects. Inactivation of Hop in the mouse is lethal in half of the expected null embryos. Here, we show that Hop is expressed strongly in the adult CCS. Hop-/- adult mice display conduction defects below the atrioventricular node (AVN) as determined by invasive electrophysiological testing. These defects are associated with decreased expression of connexin40. Our results suggest that Hop functions in the adult CCS and demonstrate conservation of molecular hierarchies between embryonic myocardium and the specialized conduction tissue of the mature heart.