PDF(Pubmed)
Abstract：
UNASSIGNED: RAB27A is a member of the RAS oncogene superfamily of GTPases and regulates cell secretory function. It, is expressed within blood vessels and perivascular adipose tissue. We hypothesized that loss of RAB27A would alter cardiovascular function.
UNASSIGNED: Body weight of Rab27aash mice was measured from 2 to 18 months of age, along with glucose resorption at 6 and 12 months of age and glucose sensitivity at 18 months of age. Body weight and cellular and molecular features of perivascular adipose tissue and aortic tissue were examined in a novel C57BL/6J Rab27a null strain. Analyses included morphometric quantification and proteomic analyses. Wire myography measured vasoreactivity, and echocardiography measured cardiac function. Comparisons across ages and genotypes were evaluated via 2-way ANOVA with multiple comparison testing. Significance for myography was determined via 4-parameter nonlinear regression testing.
UNASSIGNED: Genome-wide association data linked rare human RAB27A variants with body mass index and glucose handling. Changes in glucose tolerance were observed in Rab27aash male mice at 18 months of age. In WT (wild-type) and Rab27a null male mice, body weight, adipocyte lipid area, and aortic area increased with age. In female mice, only body weight increased with age, independent of RAB27A presence. Protein signatures from male Rab27a null mice suggested greater associations with cardiovascular and metabolic phenotypes compared with female tissues. Wire myography results showed Rab27a null males exhibited increased vasoconstriction and reduced vasodilation at 8 weeks of age. Rab27a null females exhibited increased vasoconstriction and vasodilation at 20 weeks of age. Consistent with these vascular changes, male Rab27a null mice experienced age-related cardiomyopathy, with severe differences observed by 21 weeks of age.
UNASSIGNED: Global RAB27A loss impacted perivascular adipose tissue and thoracic aorta proteomic signatures, altered vasocontractile responses, and decreased left ventricular ejection fraction in mice.
UNASSIGNED: Body weight of Rab27aash mice was measured from 2 to 18 months of age, along with glucose resorption at 6 and 12 months of age and glucose sensitivity at 18 months of age. Body weight and cellular and molecular features of perivascular adipose tissue and aortic tissue were examined in a novel C57BL/6J Rab27a null strain. Analyses included morphometric quantification and proteomic analyses. Wire myography measured vasoreactivity, and echocardiography measured cardiac function. Comparisons across ages and genotypes were evaluated via 2-way ANOVA with multiple comparison testing. Significance for myography was determined via 4-parameter nonlinear regression testing.
UNASSIGNED: Genome-wide association data linked rare human RAB27A variants with body mass index and glucose handling. Changes in glucose tolerance were observed in Rab27aash male mice at 18 months of age. In WT (wild-type) and Rab27a null male mice, body weight, adipocyte lipid area, and aortic area increased with age. In female mice, only body weight increased with age, independent of RAB27A presence. Protein signatures from male Rab27a null mice suggested greater associations with cardiovascular and metabolic phenotypes compared with female tissues. Wire myography results showed Rab27a null males exhibited increased vasoconstriction and reduced vasodilation at 8 weeks of age. Rab27a null females exhibited increased vasoconstriction and vasodilation at 20 weeks of age. Consistent with these vascular changes, male Rab27a null mice experienced age-related cardiomyopathy, with severe differences observed by 21 weeks of age.
UNASSIGNED: Global RAB27A loss impacted perivascular adipose tissue and thoracic aorta proteomic signatures, altered vasocontractile responses, and decreased left ventricular ejection fraction in mice.
摘要：
■RAB27A,分泌的调节剂，在血管和血管周围脂肪组织中表达。我们假设RAB27A的缺失会改变心血管功能。
■Rab27aash小鼠的体重从2到18月龄测量，以及6个月和12月龄时的葡萄糖吸收和18月龄时的葡萄糖敏感性。在新型C57BL/6JRab27a无效菌株中检查了血管周围脂肪组织和主动脉组织的体重以及细胞和分子特征。分析包括形态定量和蛋白质组学分析。测量血管反应性的线肌电图,和超声心动图测量心脏功能。通过具有多重比较测试的双向ANOVA评估年龄和基因型之间的比较。通过4参数非线性回归测试确定肌电图的重要性。
■全基因组关联数据将罕见的人类RAB27A变异与体重指数和葡萄糖处理联系起来。在18月龄的Rab27aash雄性小鼠中观察到葡萄糖耐量的变化。在WT（野生型）和Rab27a空雄性小鼠中，体重,脂肪细胞脂质面积，主动脉面积随年龄增加而增加。在雌性老鼠中，只有体重随着年龄的增长而增加，独立于RAB27A的存在。来自雄性Rab27a无效小鼠的蛋白质特征表明与雌性组织相比与心血管和代谢表型的更大关联。线肌电图结果显示，Rab27a无效雄性在8周龄时表现出血管收缩增加和血管舒张减少。Rab27a无效雌性在20周龄时表现出增加的血管收缩和血管舒张。与这些血管变化一致，雄性Rab27a空小鼠经历了年龄相关性心肌病，在21周龄时观察到严重的差异。
■全球RAB27A损失影响血管周围脂肪组织和胸主动脉蛋白质组特征，血管收缩反应改变,小鼠左心室射血分数降低。
■Rab27aash小鼠的体重从2到18月龄测量，以及6个月和12月龄时的葡萄糖吸收和18月龄时的葡萄糖敏感性。在新型C57BL/6JRab27a无效菌株中检查了血管周围脂肪组织和主动脉组织的体重以及细胞和分子特征。分析包括形态定量和蛋白质组学分析。测量血管反应性的线肌电图,和超声心动图测量心脏功能。通过具有多重比较测试的双向ANOVA评估年龄和基因型之间的比较。通过4参数非线性回归测试确定肌电图的重要性。
■全基因组关联数据将罕见的人类RAB27A变异与体重指数和葡萄糖处理联系起来。在18月龄的Rab27aash雄性小鼠中观察到葡萄糖耐量的变化。在WT（野生型）和Rab27a空雄性小鼠中，体重,脂肪细胞脂质面积，主动脉面积随年龄增加而增加。在雌性老鼠中，只有体重随着年龄的增长而增加，独立于RAB27A的存在。来自雄性Rab27a无效小鼠的蛋白质特征表明与雌性组织相比与心血管和代谢表型的更大关联。线肌电图结果显示，Rab27a无效雄性在8周龄时表现出血管收缩增加和血管舒张减少。Rab27a无效雌性在20周龄时表现出增加的血管收缩和血管舒张。与这些血管变化一致，雄性Rab27a空小鼠经历了年龄相关性心肌病，在21周龄时观察到严重的差异。
■全球RAB27A损失影响血管周围脂肪组织和胸主动脉蛋白质组特征，血管收缩反应改变,小鼠左心室射血分数降低。
