Matrix metallopeptidase 9 and placental growth factor may correlate with collateral status based on whole-brain perfusion combined with multiphase computed tomography angiography

ABSTRACT

Objective

The aim of this study was to find out the relationship between serum biomarkers and cerebral collateral status in acute ischemic stroke with cerebral large artery atherosclerosis.

Methods

We enrolled patients with ischemic stroke due to large artery atherosclerosis within 7 days of symptom onset, age 18–80 years, from August 2016 to December 2017. Twelve biomarkers representing different pathophysiological mechanisms were tested after admission. Whole-brain perfusion combined with multiphase computed tomography angiography was performed to assess cerebral collateral structure and function.

Results

Fifty-two patients completed the test of candidate biomarkers and recruited in this study. The mean age was 55.0 (11.1) years, 42 (80.8%) patients were male, 20 (38.5%) had poor collateral, 36 (69.2%) patients had anterior circulation stenosis or occlusion. Compared with poor collateral group, the level of MMP-9 (135,475.00 pg/ml vs. 103,612.00 pg/ml, p = 0.040) and PGF (5.75 pg/ml vs. 3.46 pg/ml, p = 0.046) was significantly higher in good collateral group. The adjusted OR (95%CI) of MMP-9 and PGF were 5.533 (1.10–27.74, p = 0.038), 7.73 (1.41–42.39, p = 0.018), respectively. sTie-2 level had a positive correlation with proportion of Tmax 4–6 (r = 0.302, p = 0.033) and HMW-KGN had negative correlation with proportion of Tmax 6–8 (r = −0.338, p = 0.02). After adjustment, the correlation of sTie-2 level and proportion of Tmax 4–6 was statistically significant (p = 0.003), and correlation of HMW-KGN and Tmax6-8 was not statistically significant (p = 0.056).

Discussion

Serum PGF and MMP-9 levels may correlate with collateral status based on MP-CTA in acute ischemic stroke patients with cerebral large artery atherosclerosis. Higher PGF and MMP-9 concentration associated with good collateral status.

KEYWORDS:

• Cerebral large artery atherosclerosis
• collateral
• multiphase cta
• biomarkers

Supplementary material

Supplemental data for this article can be accessed here.

Acknowledgments

We thank our colleagues on Dr Liu’s research team and physicians in the Department of Neurology in Beijing Tiantan Hospital. BY & YD was responsible for writing the manuscript. XL conceived of the study design and provided critical review of the manuscript. YP provided critical review of the manuscript. LL conceived of the study design and provided critical review of the manuscript. All authors approved the final version of the manuscript. We also thank all the patients and their families involved.

Disclosure of potential conflicts of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Statement of ethics

All participants (or their legal representative) have given their written informed consent. The protocol was approved by the Ethics Committee of Beijing Tiantan Hospital.

Additional information

Funding

Supported by the National Natural Science Foundation of China (81870913), and the National Key R&D program of China (2016YFC1307301).

Notes on contributors

Bo Yang

Bo Yang, MD, attending doctor of neurology department, Beijing Tiantan Hospital of Capital Medical University, focuses on intensive care for stroke.

Yarong Ding

Yarong Ding, a post-graduate of Capital Medical University, is now undertaking clinical practice and research in Beijing Tiantan Hospital, the main research area is cerebrovascular diseases.

Xin Liu

Xin Liu, MD, PhD, resident doctor of neurology department, Beijing Tiantan Hospital of Capital Medical University, the main research area is cerebrovascular diseases.

Yuan Cai

Yuan Cai, a master student of Beijing Tiantan Hospital of Capital Medical University; the main research area is cerebrovascular diseases.

Xinxuan Yang

Xinxuan Yang, a master student of Beijing Tiantan Hospital of Capital Medical University; the main research area is cerebrovascular diseases.

Qixuan Lu

Qixuan Lu, a master student of Beijing Tiantan Hospital of Capital Medical University; the main research area is cerebrovascular diseases.

Weibin Gu

Weibin Gu, MD, PhD, attending doctor of Department of Radiology, Beijing Tiantan Hospital of Capital Medical University.

Liping Liu

Liping Liu, MD, PhD, professor of Neurology Department of Beijing Tiantan Hospital Affiliated to Capital Medical University, mainly focuses on intensive care for stroke, cerebrovascular disease.

Yuehua Pu

Yuehua Pu, MD, PhD, attending doctor of Neurology Department, Beijing Tiantan Hospital of Capital Medical University, mainly focuses on intracranial atherosclerosis, cerebral collateral circulation.