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The secretome of senescent preadipocytes influences the phenotype and function of cells of the vascular wall
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ( IF 6.2 ) Pub Date : 2020-09-28 , DOI: 10.1016/j.bbadis.2020.165983
Mojtaba Parvizi , Zachary C. Ryan , Sanam Ebtehaj , Bonnie K. Arendt , Ian R. Lanza

Senescent cells accumulate in numerous tissues in several chronic conditions such as aging, obesity, and diabetes. These cells are in a state of irreversible cell-cycle arrest and secrete inflammatory cytokines, chemokines and other immune modulators that have paracrine effects on nearby tissues. Adipose tissue, in particular, harbors senescent cells, which have been linked with numerous chronic conditions and age-related comorbidities. Here we performed a series of in vitro experiments to determine the influence of senescent preadipocytes on key cell types found in vessel walls, including vascular smooth muscle cells (VSMCs), endothelial cells (ECs), macrophages (MQs), and adipose-derived stromal/stem cells (ASCs). Primary human preadipocytes were irradiated to trigger a senescence-like phenotype. VSMCs, ECs, MQs, and ASCs were exposed to conditioned media collected from irradiated preadipocytes or control preadipocytes. Additional experiments were performed where VSMCs, ECs, MQs, and ASCs were co-cultured with irradiated or control preadipocytes. The secretome of irradiated cells induced an inflammatory phenotype, decreased cell viability, disrupted proliferation and migration, and impaired metabolic function of these cell types in vitro. These maladaptive changes in response to senescent cell exposure provide early evidence in support of a hypothesis that senescent preadipocytes trigger phenotypic and functional changes in key cellular components of blood vessels that may contribute to vascular disease.



中文翻译:

衰老前脂肪细胞的分泌组影响血管壁细胞的表型和功能

在衰老,肥胖和糖尿病等几种慢性疾病中,衰老细胞在许多组织中积累。这些细胞处于不可逆的细胞周期停滞状态,并分泌对附近组织具有旁分泌作用的炎性细胞因子,趋化因子和其他免疫调节剂。尤其是脂肪组织带有衰老细胞,这些衰老细胞与许多慢性病和与年龄有关的合并症有关。在这里,我们进行了一系列体外确定衰老前脂肪细胞对血管壁中关键细胞类型的影响的实验,包括血管平滑肌细胞(VSMC),内皮细胞(EC),巨噬细胞(MQ)和脂肪来源的基质/干细胞(ASC)。照射人类原代前脂肪细胞以触发衰老样表型。将VSMC,EC,MQ和ASC暴露于从辐照的前脂肪细胞或对照前脂肪细胞收集的条件培养基中。在将VSMC,EC,MQ和ASC与辐照或对照前脂肪细胞共培养的情况下,进行了其他实验。受辐照细胞的分泌组在体外诱导炎性表型,降低细胞活力,破坏增殖和迁移并损害这些细胞的代谢功能。这些对衰老细胞暴露的适应不良反应提供了早期证据,支持了以下假设:衰老前脂肪细胞会触发可能导致血管疾病的血管关键细胞成分的表型和功能性变化。

更新日期:2020-10-11
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