C1q/TNF‐related protein 9: A novel therapeutic target in ischemic stroke?

Abstract

| INTRODUC TI ONIschemic stroke and coronary atherosclerosis disease (CAD) are both kinds of atherosclerotic diseases with high morbidity and high mortality, which have already been on the spotlight in both clinic and research. Vascular lesion is the major feature in the pathogenesis of these two diseases. Initially, the endothelial cells (EC) are damaged by risk factors, followed with activated platelets, inflammatory reactions, and accelerated vessel wall remodeling. Consequently, atherosclerotic plaques forming, rupture and erosion, with different subtypes of surface thrombosis, vasospasm and distal vascular embolization, lead to ischemic lesions, including ischemic stroke and CAD. However, the molecular mechanism of vascular lesion is complicated, which requires further research for the full understanding of pathogenesis of atherosclerotic diseases.C1q/TNF-related protein 9 (CTRP9) is a newly discovered adipokine. By searching databases of Medline and Web of Science (WOS), we found only a few reports about this factor, most of which were published in the past two years. Meanwhile, they mainly expounded the role of CTRP9 in the blood vessels related pathogenesis of CAD, including regulating energy metabolism, modulating vasomotion, protecting EC, inhibiting platelet activation, inhibiting pathological vascular remodeling, stabilizing atherosclerotic plaques, and protecting heart. Here, we reviewed the genic features, proteinic features and physiologic functions of CTRP9, and proposed some possible associations between CTRP9 and ischemic stroke as well. AbstractIschemic stroke has become a serious public health problem, which is in need of advanced research on the prevention and treatment. As a newly discovered adipokine, C1q/TNF-related protein 9 (CTRP9) plays a vital role in the pathogenesis of coronary atherosclerosis disease (CAD), including regulating energy metabolism, modulating vasomotion, protecting endothelial cells, inhibiting platelet activation, inhibiting pathological vascular remodeling, stabilizing atherosclerotic plaques, and protecting heart. The present review raised a critical question of whether CTRP9 could also have the capacity of protecting the brain tissue and decreasing the severity of brain lesions in the ischemic stroke since CAD and ischemic stroke are both the major subtypes of atherosclerotic vascular diseases which share a large of common pathogenesis in the vascular lesion particularly. Therefore, we proposed that CTRP9 could be a feasible biomarker and potential therapeutic target in ischemic stroke on the basis of the reviewed research reports. K E Y W O R D Sadipokine, coronary atherosclerosis disease, CTRP9, ischemic stroke | 129 YANG et al.

Salivary cytokine profile in patients with ischemic stroke

“…Although further studies in a larger patient population are needed, TNF-α may be a potential biomarker of cognitive impairment/functional status in stroke cases. As shown in previous studies, elevated TNF-α serum level was noted already in the first few hours after the ischemic stroke 10 , 16 . Serum TNF-α also correlates with brain infarct volume and severity of neurological symptoms as well as reflects the degree of patients' functional disability 82 , 83 .…”

“…Availability of the latest diagnostic techniques (CT perfusion, MRI) is also often limited 15 . Therefore, it is not surprising that new diagnostic methods are still being sought 16 . In particular, biochemical biomarkers are being searched extensively to facilitate early diagnosis of stroke or to establish further patient’s prognosis 17 , 18 .…”

“…In particular, biochemical biomarkers are being searched extensively to facilitate early diagnosis of stroke or to establish further patient’s prognosis 17 , 18 . Given the critical role of inflammation in stroke pathogenesis, the use of cytokines and chemokines in laboratory diagnostics has been increasingly advocated 16 , 19 . Of particular note is the evaluation of TNF-α and IL-6, whose serum levels increase in the acute phase of stroke as well as correlate with its cerebrospinal fluid (CSF) levels and stroke focus size 20 – 23 .…”

Association Between Serum C1q Tumor Necrosis Factor-Related Protein 9 and the Clinical Characteristics and Prognosis of Ischemic Stroke

“…IS and CAD share considerable pathogenesis, from risk factors to vascular lesions followed by different target organ damage [19][20][21]. According to our previous review, CTRP9 could play multiple positive roles in vascular lesions in IS [4]. In addition, the ratios of blood lipid indicators to each other may likely affect the progression of atherosclerosis [22], and the LDL-C/HDL-C ratio has already been found to be superior to single lipid predictors of cardiovascular disease risk [22].…”

“…Identifying blood-derived biomarkers of stroke is an active field of research, since their potential use is not limited to diagnosis and differentiation, but can be applied to prognosis and patient monitoring, monitoring the effectiveness of applied therapy, and/or diagnosing possible complications. According to our previous review, C1q tumor necrosis factor (TNF)-related protein 9 (CTRP9) plays a vital role in the cardiovascular disease process, including regulating energy metabolism, modulating vasomotion, protecting endothelial cells, inhibiting platelet activation, inhibiting pathological vascular remodeling, stabilizing atherosclerotic plaques, and protecting the heart [ 4 ]. Hence, we proposed that CTRP9 could play multiple positive and beneficial roles in IS.…”