무증상 뇌경색에서 aspirin 복용에 따른 염증 및 혈관신생 생물표지자의 변화

Abstract

Background and purpose: Silent Brain Infarcts (SBIs), asymptomatic focal ischemic lesions on imaging modalities, are found commonly even in healthy population and are well known as a risk factor of symptomatic stroke, depression, and dementia. Researchers support the theory that lacunar infarcts and silent brain infarcts share core pathophysiology associated with inflammatory cascade. Therefore, this study aimed to find the differences in the levels of inflammation- and angiogenesis-related biomarkers between patients with SBIs and healthy controls. Furthermore, the present study sought to find the effect of aspirin on these biomarkers as aspirin is one of the most well-known secondary preventive treatments of ischemic stroke. Methods: Among patients who had visited our hospital for the evaluation of headache, vertigo, and subjective memory impairment, some of them wanted to take Magnetic Resonance Imaging (MRI) to evaluate their brain and their MR images were interpreted by neuroradiologists. We finally recruited 26 patients with SBIs and 10 healthy controls without SBIs. Plasma levels of Macrophage Migration Inhibitory Factor (MIF), Matrix Metalloproteinase-9 (MMP-9), Vascular Endothelial Growth Factor (VEGF), Chemokine C-X-C Motif Ligand 12 (CXCL12), and visfatin were measured between two groups at baseline. Patients with SBIs started to take aspirin (100mg/day) and the levels of plasma biomarkers were rechecked 3 months after medication. Results: MIF and MMP-9 levels were significantly higher in patients with SBIs than in control group. After taking aspirin, plasma level of visfatin decreased in the patient group. Biomarker levels were compared between patients with SBIs 3 months after treatment and control group at baseline. MMP-9 level was still higher and VEGF and visfatin levels were lower in the patient group. Conclusions: Inflammation could be one of the important factors in pathogenic mechanisms of silent brain infarcts just like in symptomatic ischemic stroke and aspirin affects several biomarkers related in inflammatory cascade. |무증상 뇌경색은 영상 검사를 통해 발견된 증상의 발현이 없는 국소적인 허혈병변을 뜻한다. 무증상 뇌경색은 건강한 사람에서도 흔하게 발견되며 이는 증상이 동반된 급성 뇌경색, 우울증, 치매의 위험인자로 알려져 있다. 최근 연구에 따르면 무증상 뇌경색은 병리적 발생 기전이 열공성 경색과 유사하다는 사실이 밝혀졌으며 연구자들은 여러 발병 기전 중 염증 과정 또한 유사한 형태로 일어나는 것으로 판단하고 있다. 본 연구에서는 무증상 뇌경색이 발견된 환자와 건강한 대조군 간에 염증 인자와 혈관신생 관련 인자의 차이 여부를 알아보고자 하였다. 또한 무증상 뇌경색 환자에게 뇌경색의 이차 예방 약제로 널리 알려진 aspirin을 복용하게 한 후 약제의 효과를 생물표지자의 변화로 확인하고자 하였다. 26명의 무증상 뇌경색 환자와 10명의 건강한 대조군이 최종적으로 선별되었고 생물표지자로는Plasma levels of Macrophage Migration Inhibitory Factor (MIF), Matrix Metalloproteinase-9 (MMP-9), Vascular Endothelial Growth Factor (VEGF), Chemokine C-X-C Motif Ligand 12 (CXCL12), visfatin 이 측정되었다. 환자들은 무증상 뇌경색 진단 당시부터 aspirin (100mg/day)을 복용하기 시작하였고 생물표지자는 진단 당시와 약물 복용 3개월 후 총 2회 확인하였다. 대조군에서는 선별 당시에만 생물 표지자를 측정하였다. MIF와 MMP-9 수치가 대조군에 비해 환자군에서 유의미하게 증가되어 있었다. Aspirin을 복용한 후에는 환자군에서 visfatin이 감소한 것을 확인할 수 있었다. 약제 복용 3개월 후 환자군의 생물표지자 수치와 대조군의 수치를 비교하였을 때 환자군에서 MMP-9 수치는 여전히 증가되어 있었고 VEGF와 visfatin 수치는 감소되어 있었다. 본 연구를 통해 증상이 동반된 허혈성뇌경색과 유사하게 무증상 뇌경색에서도 염증반응이 동반된다는 사실을 확인할 수 있었고 aspirin이 염증 반응에 관여함을 알 수 있었다.; Background and purpose: Silent Brain Infarcts (SBIs), asymptomatic focal ischemic lesions on imaging modalities, are found commonly even in healthy population and are well known as a risk factor of symptomatic stroke, depression, and dementia. Researchers support the theory that lacunar infarcts and silent brain infarcts share core pathophysiology associated with inflammatory cascade. Therefore, this study aimed to find the differences in the levels of inflammation- and angiogenesis-related biomarkers between patients with SBIs and healthy controls. Furthermore, the present study sought to find the effect of aspirin on these biomarkers as aspirin is one of the most well-known secondary preventive treatments of ischemic stroke. Methods: Among patients who had visited our hospital for the evaluation of headache, vertigo, and subjective memory impairment, some of them wanted to take Magnetic Resonance Imaging (MRI) to evaluate their brain and their MR images were interpreted by neuroradiologists. We finally recruited 26 patients with SBIs and 10 healthy controls without SBIs. Plasma levels of Macrophage Migration Inhibitory Factor (MIF), Matrix Metalloproteinase-9 (MMP-9), Vascular Endothelial Growth Factor (VEGF), Chemokine C-X-C Motif Ligand 12 (CXCL12), and visfatin were measured between two groups at baseline. Patients with SBIs started to take aspirin (100mg/day) and the levels of plasma biomarkers were rechecked 3 months after medication. Results: MIF and MMP-9 levels were significantly higher in patients with SBIs than in control group. After taking aspirin, plasma level of visfatin decreased in the patient group. Biomarker levels were compared between patients with SBIs 3 months after treatment and control group at baseline. MMP-9 level was still higher and VEGF and visfatin levels were lower in the patient group. Conclusions: Inflammation could be one of the important factors in pathogenic mechanisms of silent brain infarcts just like in symptomatic ischemic stroke and aspirin affects several biomarkers related in inflammatory cascade.