Bennion Douglas M, Rosado Christian A, Haltigan Emily A, Regenhardt Robert W, Sumners Colin, Waters Michael F
Department of Physiology and Functional Genomics, University of Florida, USA
Neurovascular Division, Department of Neurology, University of Florida, USA.
J Renin Angiotensin Aldosterone Syst. 2016 Aug 3;17(3). doi: 10.1177/1470320316661060. Print 2016 Jul.
Levels of angiotensin converting enzyme 2 (ACE2), a cardio and neuro-protective carboxypeptidase, are dynamically altered after stroke in preclinical models. We sought to characterize the previously unexplored changes in serum ACE2 activity of stroke patients and the mechanism of these changes. Serum samples were obtained from patients during acute ischemic stroke (n=39), conditions mimicking stroke (stroke-alert, n=23), or from control participants (n=20). Enzyme activity levels were analyzed by fluorometric assay and correlated with clinical variables by regression analyses. Serum ACE2 activity was significantly lower in acute ischemic stroke as compared to both control and stroke-alert patients, followed by an increase to control levels at three days. Serum ACE2 activity significantly correlated with the presence of ischemic stroke after controlling for other factors (P=0.01). Additional associations with ACE2 activity included a positive correlation with systolic blood pressure at presentation in stroke-alert (R(2)=0.24, P=0.03), while stroke levels showed no correlation (R(2)=0.01, P=0.50). ACE2 sheddase activity was unchanged between groups. These dynamic changes in serum ACE2 activity in stroke, which concur with preclinical studies, are not likely to be driven primarily by acute changes in blood pressure or sheddase activity. These findings provide new insight for developing therapies targeting this protective system in ischemic stroke.
血管紧张素转换酶2（ACE2）是一种具有心脏和神经保护作用的羧肽酶，在临床前模型中，中风后其水平会发生动态变化。我们试图描述中风患者血清ACE2活性此前未被探索的变化及其机制。在急性缺血性中风患者（n = 39）、模拟中风的情况（中风预警，n = 23）或对照参与者（n = 20）中采集血清样本。通过荧光测定法分析酶活性水平，并通过回归分析将其与临床变量相关联。与对照患者和中风预警患者相比，急性缺血性中风患者的血清ACE2活性显著降低，随后在三天时升高至对照水平。在控制其他因素后，血清ACE2活性与缺血性中风的存在显著相关（P = 0.01）。与ACE2活性的其他关联包括中风预警患者就诊时收缩压与ACE2活性呈正相关（R² = 0.24，P = 0.03），而中风患者组则无相关性（R² = 0.01，P = 0.50）。各组之间ACE2裂解酶活性无变化。中风患者血清ACE2活性的这些动态变化与临床前研究一致，不太可能主要由血压或裂解酶活性的急性变化驱动。这些发现为开发针对缺血性中风中这种保护系统的治疗方法提供了新的见解。
