Dylan Burger ，Rhian M Touyz      加拿大渥太华大学    英国格拉斯哥大学
　　Originally described as inert "cellular dust，"  cell membrane-derived microparticles are now considered as biomarkers of disease as well as vectors to transfer biological messages between cells. Microparticles (MP) are extracellular vesicles that are formed by outward directed blebbing of the cell membrane and are produced in response to cell stresses， including apoptosis and cell stimulation. Circulating levels of MPs are increased in cardiovascular disease associated with inflammation and endothelial dysfunction and as such have been considered as biomarkers of disease.  In plasma samples， microparticles of endothelial， platelet， erythrocyte， and leukocyte origin can be detected and levels are correlated with measures of endothelial dysfunction. In diabetes， pulmonary hypertension and end-stage kidney disease， MPs have been reported to predict risk of future adverse cardiovascular events， although this has yet to be confirmed in hypertensive patients.
　　Amongst the various MP populations， endothelial MPs are most consistently reported to increase in both experimental models and in patients with cardiovascular disease.  Elevations in platelet， monocyte， and erythrocyte-derived MPs have also been observed and may reflect an underlying pro-coagulant， pro-inflammatory state.  Our laboratory has reported that angiotensin II-infused mice exhibit significant increases in endothelial and total MPs. Similarly， aldosterone-salt treatment has been reported to increase total， endothelial， platelet， and erythrocyte-derived MPs. Clinically， endothelial， monocyte， and platelet-derived MPs have been found to be increased in hypertensive patients and this increase may be attenuated with antihypertensive therapy.
　　An emerging concept in MP biology is the potential for MPs to act as molecular signals and regulators of biological events. For example， we have reported that MPs can act on endothelial cells to promote oxidative stress， inflammation， and senescence. MPs of various origins have also been reported to promote apoptosis， impair angiogenesis， impair vasorelaxation， and promote coagulation. Of note， increases in phosphatidylserine-positive MPs in patients with essential hypertension has been implicated in the perpetuation of a prothrombotic state.
　　In summary， MPs are both markers of and active players in endothelial injury and may contribute to the progressive decline in vascular health seen in hypertension. Although an exciting area of research， there are still many unanswered questions with regards to MPs and hypertension. Firstly， it is unclear whether elevations in MPs in hypertensive patients predict future cardiovascular risk as they do in other populations. Secondly， it is unclear to what extent MPs contribute to progressive vascular dysfunction in vivo and whether this process may be exploited therapeutically.  Finally， whether specific phenotypic changes may occur to MPs during the development of hypertension is not known. If such changes do occur it may be that the true utility of MPs as biomarkers lies in providing a snapshot of underlying cellular and molecular processes.  Such information could prove invaluable in directing therapeutic and diagnostic decisions.
　　最初被描述为惰性“细胞灰尘”的细胞膜衍生微粒现在被视为疾病的生物标志物以及细胞之间传递生物信息的载体。微粒是由细胞膜向外起泡形成的细胞外小囊泡，作为对细胞应激包括凋亡和细胞刺激的应答。在与炎症和内皮功能障碍相关的心血管疾病中，微粒的循环水平升高，因此被视为疾病的生物标志物。在血浆样本中，内皮细胞、血小板、红细胞和白细胞起源的微粒可以被检测到，其水平与内皮功能障碍的检测值有关。糖尿病、肺动脉高压和终末期肾病中，有报道微粒可预测未来不良心血管事件风险，但这尚未在高血压患者中证实。
　　各种微粒群中，在实验模型和心血管疾病患者中，内皮细胞微粒升高的报道最为一致。血小板、单核细胞和红细胞来源的微粒升高也已被观察到，这可能反映潜在的促凝促炎状态。我们的实验室报告，输注血管紧张素II的小鼠表现出内皮细胞和总微粒显著增加。与此相似，醛固酮-盐处理增加总体、内皮细胞、血小板和红细胞来源的微粒。临床发现高血压患者内皮细胞、单核细胞和血小板来源的微粒增加，抗高血压治疗可削弱这种增加。
　　微粒生物学中一个新兴的概念是微粒作为分子信号和生物事件调节因子的可能性。例如，我们曾经报道微粒可作用于内皮细胞，促进氧化应激、炎症和衰老。据报道，不同来源的微粒可促进凋亡、损害血管新生、损害血管舒张并促进凝血。值得注意的是，原发性高血压患者中磷脂酰丝氨酸阳性的微粒升高意味着促血栓状态持续存在。
　　总之，内皮损伤中，微粒既是标志物，也是积极参与者，且可能促成高血压患者血管健康的不断减退。尽管这是一个令人兴奋的研究领域，对微粒和高血压仍有许多悬而未决的问题。首先，尚不清楚在高血压患者中微粒的升高是否与在其他人群中一样可以预测未来心血管风险。其次，尚不清楚微粒在体内以何种程度促成进行性血管功能障碍，以及是否可能利用这个过程寻找治疗方法。最后，尚不知在高血压发展期间微粒是否可能发生特定的表型改变。如果的确发生了这样的改变，则微粒作为生物标志物的真正效用可能在于提供了潜在细胞和分子过程的快照。在指导治疗和诊断决策上，这种信息可能非常宝贵。