Subcellular pathways shared by afflicted patients and mutant mice identify a new drug treatment for aortic aneurysm in Marfan syndrome

We analyzed differentially expressed genes in smooth muscle cells derived from the thoracic aorta of Marfan Syndrome (MFS) patients and control subjects to identify cell biological mechanisms contributing to thoracic aoritc aneurysm (TAA) development and rupture. These mechanisms were used to identify a potential drug treatment to mitigate TAA progression. We analyzed differentially expressed genes in whole aorta of P16 MFS mice vs WT mice to identify cell biological mechanisms contributing to thoracic aoritc aneurysm (TAA) development and rupture. These mechanisms were used to identify baclofen as a potential drug treatment to mitigate TAA progression. The effect of baclofen on gene expression in WT and MFS was documented in P60 mice that received treatment since P16. Identification of differentially expressed genes in smooth muslce cells derived from the aorta of Marfan Syndrome patients. Identification of differentially expressed genes in thoracic aortic wall of MFS vs WT mice and of baclofen treated MFS/WT mice vs untreated MFS WT mice.本研究分析了马凡综合征（Marfan Syndrome, MFS）患者与对照受试者胸主动脉来源的平滑肌细胞中的差异表达基因，以明确参与胸主动脉瘤（thoracic aortic aneurysm, TAA）发生与破裂的细胞生物学机制，并基于上述机制筛选可缓解TAA进展的潜在药物治疗方案。我们还分析了P16龄MFS小鼠与野生型（WT）小鼠的全主动脉组织差异表达基因，以揭示参与胸主动脉瘤发生与破裂的细胞生物学机制，并基于该机制确定巴氯芬（baclofen）为可缓解TAA进展的潜在药物。我们对自P16龄起接受给药处理的P60龄小鼠，验证了巴氯芬对野生型与MFS模型小鼠基因表达的调控作用。本研究还完成了三项差异表达基因分析：其一为马凡综合征患者主动脉来源平滑肌细胞的差异表达基因分析；其二为MFS小鼠与WT小鼠胸主动脉壁的差异表达基因分析；其三为巴氯芬处理组MFS/WT小鼠与未处理组MFS/WT小鼠的差异表达基因分析。