Dataset Information

Human Urinary Kallidinogenase Promotes Angiogenesis and Cerebral Perfusion in Experimental Stroke.

ABSTRACT: Angiogenesisis a key restorative mechanism in response to ischemia, and pro-angiogenic therapy could be beneficial in stroke. Accumulating experimental and clinical evidence suggest that human urinary kallidinogenase (HUK) improves stroke outcome, but the underlying mechanisms are not clear. The aim of current study was to verify roles of HUK in post-ischemic angiogenesis and identify relevant mediators. In rat middle cerebral artery occlusion (MCAO) model, we confirmed that HUK treatment could improve stroke outcome, indicated by reduced infarct size and improved neurological function. Notably, the 18F-FDG micro-PET scan indicated that HUK enhanced cerebral perfusion in rats after MCAO treatment. In addition, HUK promotespost-ischemic angiogenesis, with increased vessel density as well as up-regulated VEGF andapelin/APJ expression in HUK-treated MCAO mice. In endothelial cell cultures, induction of VEGF and apelin/APJ expression, and ERK1/2 phosphorylation by HUK was further confirmed. These changes were abrogated by U0126, a selective ERK1/2 inhibitor. Moreover, F13A, a competitive antagonist of APJ receptor, significantly suppressed HUK-induced VEGF expression. Furthermore, angiogenic functions of HUK were inhibited in the presence of selective bradykinin B1 or B2 receptor antagonist both in vitro and in vivo. Our findings indicate that HUK treatment promotes post-ischemic angiogenesis and cerebral perfusion via activation of bradykinin B1 and B2 receptors, which is potentially due to enhancement expression of VEGF and apelin/APJ in ERK1/2 dependent way.

SUBMITTER: Han L

PROVIDER: S-EPMC4519127 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Human Urinary Kallidinogenase Promotes Angiogenesis and Cerebral Perfusion in Experimental Stroke.

Han Lijuan L Li Jie J Chen Yanting Y Zhang Meijuan M Qian Lai L Chen Yan Y Wu Zhengzheng Z Xu Yun Y Li Jingwei J

PloS one 20150729 7

Angiogenesisis a key restorative mechanism in response to ischemia, and pro-angiogenic therapy could be beneficial in stroke. Accumulating experimental and clinical evidence suggest that human urinary kallidinogenase (HUK) improves stroke outcome, but the underlying mechanisms are not clear. The aim of current study was to verify roles of HUK in post-ischemic angiogenesis and identify relevant mediators. In rat middle cerebral artery occlusion (MCAO) model, we confirmed that HUK treatment could ...[more]

PMID: 26222055

Similar Datasets

Project description:New treatments for cerebral small-vessel disease are needed to reduce the risk of small-vessel occlusion stroke and vascular cognitive impairment. We investigated an approach targeted to the signalling molecule cyclic guanosine monophosphate, using the phosphodiesterase 5 inhibitor tadalafil, to explore if it improves cerebral blood flow and endothelial function in patients with cerebral small-vessel disease and stroke. In a randomized, double-blinded, placebo-controlled, cross-over pilot trial (NCT02801032), we included patients who had a previous (>6?months) small-vessel occlusion stroke. They received a single dose of either 20?mg tadalafil or placebo on 2 separate days at least 1?week apart. We measured the following: baseline MRI for lesion load, repeated measurements of blood flow velocity in the middle cerebral artery by transcranial Doppler, blood oxygen saturation in the cortical microvasculature by near-infrared spectroscopy, peripheral endothelial response by EndoPAT and endothelial-specific blood biomarkers. Twenty patients with cerebral small-vessel disease stroke (3 women, 17 men), mean age 67.1?±?9.6, were included. The baseline mean values ± standard deviations were as follows: blood flow velocity in the middle cerebral artery, 57.4?±?10.8?cm/s; blood oxygen saturation in the cortical microvasculature, 67.0?±?8.2%; systolic blood pressure, 145.8?±?19.5?mmHg; and diastolic blood pressure, 81.3?±?9.1?mmHg. We found that tadalafil significantly increased blood oxygen saturation in the cortical microvasculature at 180?min post-administration with a mean difference of 1.57?±?3.02%. However, we saw no significant differences in transcranial Doppler measurements over time. Tadalafil had no effects on peripheral endothelial function assessed by EndoPAT and endothelial biomarker results conflicted. Our findings suggest that tadalafil may improve vascular parameters in patients with cerebral small-vessel disease stroke, although the effect size was small. Increased oxygenation of cerebral microvasculature during tadalafil treatment indicated improved perfusion in the cerebral microvasculature, theoretically presenting an attractive new therapeutic target in cerebral small-vessel disease. Future studies of the effect of long-term tadalafil treatment on cerebrovascular reactivity and endothelial function are needed to evaluate general microvascular changes and effects in cerebral small-vessel disease and stroke.

Dataset Information

Human Urinary Kallidinogenase Promotes Angiogenesis and Cerebral Perfusion in Experimental Stroke.

Publications

Human Urinary Kallidinogenase Promotes Angiogenesis and Cerebral Perfusion in Experimental Stroke.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets