Up-regulation of angiotensin-converting enzyme in response to acute ischemic stroke via ERK/NF-κB pathway in spontaneously hypertensive rats.

Zhou Ou,Xue-Ling Zhang,Meng-Xing Tao,Qing Gao,Yang Yang,Jun-Shan Zhou,Ying-Dong Zhang

doi:10.18632/oncotarget.21156

Abstract

Cerebral ischemic stroke is usually caused by a temporary or permanent decrease in blood supply to the brain. Despite general progress in diagnosis and treatment, the prognosis of stroke is still unsatisfactory, and more detailed potential mechanisms are needed to investigate underlying the pathological process. Here, we showed that serum angiotensin-converting enzyme (ACE) concentration was positively correlated with infarct volume after acute ischemic stroke (AIS). Moreover, using a permanent middle cerebral artery occlusion rat model, we indicated for the first time that increased ACE expression in response to AIS was regulated by the ERK/NF-κB pathway in peri-infarct regions. More importantly, we disclosed that angiotensin II type 1 receptors were implicated in up-regulation of ACE expression in peri-infarct regions. These findings offer insight into ACE expression and activity in response to stroke, and further our understanding of ACE mechanisms.

Highlights

Acute cerebral infarction, the leading cause of death in the world, is usually caused by a temporary or permanent decrease in the blood supply to the brain [1, 2]
Serum angiotensin-converting enzyme (ACE) levels were restored to normal levels in both the large volume and small volume groups, similar to control subjects, at 7 days after acute ischemic stroke (AIS), indicating that serum ACE levels were closely correlated with infarct volume
Numerous clinical researches have done about the relationship between ACE and AIS, no findings to date have shown whether serum ACE concentration and infarct volume after AIS are directly associated

Summary

Introduction

The leading cause of death in the world, is usually caused by a temporary or permanent decrease in the blood supply to the brain [1, 2]. Prior studies revealed that ACE was implicated in the pathological process of brain ischemic injury as well as cardiovascular disorders [6,7,8]. In contrast, a previous study from Catto and colleagues found that serum ACE activity were markedly reduced during the acute phase of cerebral infarction [10]. In this regard, these controversial findings lead to the challenge of whether ACE inhibitors can be used for anti-hypertension, and inhibit ACE activity in the days following AIS

Methods

Results

Conclusion