| Background and objectiveRupture of Intracranial aneurysm (ICA) is the leading cause of spontaneous subarachnoid hemorrhage, which features high fatality and disability rate as well as serious complications, posing serious threat to the lives of patients. However, the occurrence, development, rupture, healing process and recurrence of ICA are still poorly understood. Pathological changes of ICA include the reduction and destruction of endothelial cells, destruction and thinning of the internal elastic lamina and arterial membrane, among which dysfunction and destruction of intima are considered to be the earliest pathological changes in the development of ICA and is believed to be the initial stage of ICA. Surgical clipping and endovascular intervention are two major treatment methods for ICA. The application of endovascular intervention has been successfully switched from aneurysm embolization to parent artery reconstruction, and the latter gradually become a mainstream treatment.Endothelial progenitor cells (Endothelial progenitor cells, EPCs) are precursor cells with migratory characteristics. They can differentiate into mature endothelial cells through directed proliferation. These cells mainly originate from the bone marrow and present in small amount in peripheral blood. Under certain physiological and pathological conditions, EPCs in the bone marrow can be mobilized into the peripheral blood and thereby arrive at the targeted site, differentiating into vascular endothelial cells by vasculogenesis and angiogenesis mechanisms to refresh and repair aging and damaged endothelial cells, which play an important role in angiogenesis and maintaining vascular homeostasis.They are vital to angiogenesis and reendothelialization of damaged blood vessels. They can maintain endometrial integrity by replacing dysfunctional and damaged endothelial cells. Therefore, these cells have been identified as an effective marker to evaluate vascular endothelial function. Endogenous factors, exogenous cytokines and drugs can promote EPCs mobilization.Stromal cell derived factor-1(SDF-1α), a member of chemokine CXC subfamily, is known as the only natural chemokine which can bind and activate the receptor CXCR4.SDF-1α and CXCR4, widely and constitutively expressed in a variety of cells and tissues, are not only produced in the stromal cells of bone marrow, but also in the liver, spleen, lymph nodes, kidney, brain as well as other tissues and organs. They play key roles in the development of the circulatory system and the central nervous system, participate in various physiological and pathological processes, particularly in stem/progenitor cells homing. SDF-1is known as the most capable hematopoietic stem/progenitor cell chemokine.CXCR4, the only receptor of SDF-1α, can be highly expressed in EPCs surface and plays a vital role in the EPCs’mobilization from bone marrow into the blood as well as proceeding to the specific site.Occurrence of ICA may be closely related to the decline of number and function of circulating endothelial progenitor cells—an endogenous protective mechanism. Mechanism of occurrence and development of EPC-involved ICA remains to be studied in China and foreign countries. Through case-control and clinical cohort study, this experiment was designed to shed a light on the prevention and treatment of unruptured intracranial aneurysms by comparing quantity, function and regulatory factors of EPCs in peripheral blood between ICA patients and normal adults.MethodThe number of EPCs and concentration of SDF-1a in peripheral blood were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA) respectively. EPCs in peripheral blood were cultured in vitro and tested for functional evaluation (adhesion and migration). Normal adults, patients with unruptured aneurysms before surgery were examined respectively for further study of the relationship between the number and function of EPCs in peripheral blood and the unruptured aneurysm.ResultsShown in case-control study:The number of EPCs in peripheral blood of patients with unruptured intracranial aneurysms was significantly lower than that of normal adults. The flow cytometry analysis showed that, the percentages of CD34+/CD133+/VEGFR-2+cells were32.4±3.5vs71.8±5.4(P<0.05), exhibiting obvious differences.The concentration of SDF-1αin peripheral blood of patients with unruptured intracranial aneurysms was significantly lower than that of normal adults (2.323±0.352vs.2.563±0.404ng/mL, P<0.05), exhibiting obvious differences. As indicated in in-vitro culture of EPC:The adhesion test:compared with normal control group the number of EPCs in peripheral blood of ICA patients significantly decreased (26.5±7.8vs.76.4±7.5Ge, P<0.05), showing obvious differences. The migration test:compared with normal control group, the number of EPCs in peripheral blood of ICA patients significantly decreased (12.0±2.9vs.23.6±6.5, P <0.05), showing obvious differences.ConclusionThrough case-control study, it is found that the number and function of EPCs (adhesion, migration) and concentration of SDF-1α, a regulatory factor, in peripheral blood of patients with unruptured intracranial aneurysms are significantly lower than that of normal population. It is reasonable to conclude that the levels of EPCs and SDF-la can be used as the reference index in diagnosis and treatment of intracranial aneurysms. The damage of this endogenous injury repair mechanism may be associated with the occurrence of ICA and, taking this study into consideration, a new theory for etiology of aneurysm as well as a new means for delaying the development of lesions and effective conservative treatment can be provided. |
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