Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen, Norway.
Cardiovasc Res. 2010 Jan 1;85(1):9-16. doi: 10.1093/cvr/cvp266.
A range of inflammatory conditions is associated with pathologically high levels of circulating chromogranin A (CgA). This prohormone belongs to the family of uniquely acidic proteins co-stored and co-secreted with other hormones and peptides from the diffuse neuroendocrine system. Two highly conserved, CgA-derived peptides, vasostatin-I and catestatin, have been implicated as modulators of a wide range of cells and tissues, including those of the cardiovascular system. This review focuses on links between elevated circulating CgA and cardiovascular dysfunctions in inflammatory conditions in relation to potential beneficial effects of vasostatin-I and catestatin. Characteristic membrane-penetrating properties have been assigned to both peptides, and pertussis toxin sensitivity is shared by a number of their responses, notably in the vascular and cardiac endothelium. Pertussis toxin-sensitive, receptor-independent activation via heterotrimeric G proteins and Galphai/o subunits will be discussed as possible mechanisms for inhibitory effects of vasostatin-I and catestatin on vascular and cardiac responses. The accumulated evidence provides convincing support for vasostatin-I and catestatin as regulatory peptides for the cardiovascular system, converging on alleviation of significant dysfunctions as part of several inflammatory conditions.
一系列炎症状态与循环中嗜铬粒蛋白 A（CgA）病理性升高有关。这种前激素属于独特酸性蛋白家族，与来自弥散神经内分泌系统的其他激素和肽共同储存和共同分泌。两种高度保守的 CgA 衍生肽，即血管抑肽-I 和卡替肽，被认为是广泛的细胞和组织的调节剂，包括心血管系统。这篇综述重点关注炎症状态下循环 CgA 升高与心血管功能障碍之间的联系，以及血管抑肽-I 和卡替肽的潜在有益作用。这两种肽都具有特征性的膜穿透特性，并且许多反应都具有百日咳毒素敏感性，特别是在血管和心脏内皮中。我们将讨论百日咳毒素敏感的、受体非依赖性的通过异三聚体 G 蛋白和 Galphai/o 亚基的激活，作为血管抑肽-I 和卡替肽对血管和心脏反应的抑制作用的可能机制。积累的证据为血管抑肽-I 和卡替肽作为心血管系统的调节肽提供了令人信服的支持，它们汇聚在一起缓解几种炎症状态下的显著功能障碍。
