Guibert Christelle, Marthan Roger, Savineau Jean-Pierre
Université Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux, France.
Curr Pharm Des. 2007;13(24):2443-55. doi: 10.2174/138161207781368585.
Pulmonary arterial hypertension (PAH) is a disease characterized by a progressive increase in pulmonary arterial pressure leading to right ventricular hypertrophy, right heart failure and ultimately to death. PAH is a disease of small pulmonary arteries inducing vascular narrowing leading to a progressive increase in pulmonary vascular resistance. The therapeutic means that improve PAH are still very limited and are too often restricted to heart/lungs transplantation. Numerous forms of pulmonary hypertension exist. Although it is still unclear as to all types of PAH share a common pathogenesis, it is generally admitted that pulmonary vasoconstriction and remodelling of the arterial wall are key events. In this review, we discuss pulmonary artery smooth muscle cells (PASMC) ion channels implication in both phenomena and we examine whether variations in expression and/or the activity of these channels can contribute to the development of PAH with special attention to K(+), Cl(-) and voltage- and non voltage-activated Ca(2+) channels. For each family of ion channels, we describe their implication in the control of both membrane potential and resting cytosolic calcium concentration which are key parameters of PASMC in PAH. We also provide evidence for an implication of these channels in not only vasoconstriction but also proliferation and/or decreased apoptosis of PASMC, phenomena which contribute to remodelling of pulmonary arterial wall. In this respect, PAH may be considered as form of vascular "channelopathy". Finally, we present examples of some substances acting on ion channels and thus potentially constituting innovative therapeutic approaches of PAH.
肺动脉高压（PAH）是一种以肺动脉压力进行性升高为特征的疾病，可导致右心室肥厚、右心衰竭，最终导致死亡。PAH是一种小肺动脉疾病，可导致血管狭窄，进而使肺血管阻力进行性增加。改善PAH的治疗手段仍然非常有限，且常常局限于心肺移植。存在多种形式的肺动脉高压。尽管目前尚不清楚所有类型的PAH是否具有共同的发病机制，但一般认为肺血管收缩和动脉壁重塑是关键事件。在本综述中，我们讨论肺动脉平滑肌细胞（PASMC）离子通道在这两种现象中的作用，并研究这些通道的表达和/或活性变化是否有助于PAH的发展，特别关注钾离子（K⁺）、氯离子（Cl⁻）以及电压门控和非电压门控钙离子（Ca²⁺）通道。对于每个离子通道家族，我们描述它们在控制膜电位和静息胞质钙浓度方面的作用，而这两个参数是PAH中PASMC的关键参数。我们还提供证据表明这些通道不仅参与血管收缩，还参与PASMC的增殖和/或凋亡减少，这些现象有助于肺动脉壁的重塑。在这方面，PAH可被视为一种血管“通道病”形式。最后，我们列举了一些作用于离子通道的物质的例子，这些物质因此可能构成PAH的创新治疗方法。
