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Abstract：
Despite advancements in elucidating biological mechanisms of cardiovascular remodeling, cardiovascular disease (CVD) remains the leading cause of death worldwide. When stratified by sex, clear differences in CVD prevalence and mortality between males and females emerge. Regional differences in phenotype and biological response of cardiovascular cells are important for localizing the initiation and progression of CVD. Thus, to better understand region and sex differences in CVD presentation, we have focused on characterizing in vitro behaviors of primary vascular smooth muscle cells (VSMCs) from the thoracic and abdominal aorta of male and female mice. VSMC contractility was assessed by traction force microscopy (TFM; single cell) and collagen gel contraction (collective) with and without stimulation by transforming growth factor-beta 1 (TGF-β1) and cell proliferation was assessed by a colorimetric metabolic assay (MTT). Gene expression and TFM analysis revealed region- and sex-dependent behaviors, whereas collagen gel contraction was consistent across sex and aortic region under baseline conditions. Thoracic VSMCs showed a sex-dependent sensitivity to TGF-β1-induced collagen gel contraction (female > male; p = 0.025) and a sex-dependent proliferative response (female > male; p < 0.001) that was not apparent in abdominal VSMCs. Although primary VSMCs exhibit intrinsic region and sex differences in biological responses that may be relevant for CVD presentation, several factors-such as inflammation and sex hormones-were not included in this study. Such factors should be included in future studies of in vitro mechanobiological responses relevant to CVD differences in males and females.
摘要：
尽管在阐明心血管重塑的生物学机制方面取得了进展，心血管疾病（CVD）仍然是全球主要的死亡原因。当按性别分层时，男性和女性之间的CVD患病率和死亡率存在明显差异。心血管细胞表型和生物学反应的区域差异对于定位CVD的起始和进展很重要。因此，为了更好地理解CVD表现的地区和性别差异，我们专注于表征雄性和雌性小鼠胸主动脉和腹主动脉原代血管平滑肌细胞（VSMC）的体外行为。通过牵引力显微镜（TFM;单细胞）和胶原凝胶收缩（集体）评估VSMC的收缩性，有或没有转化生长因子β1（TGF-β1）的刺激，并通过比色代谢测定（MTT）评估细胞增殖。基因表达和TFM分析揭示了区域和性别依赖性行为，而在基线条件下,胶原凝胶收缩在性别和主动脉区域是一致的.胸部VSMC显示对TGF-β1诱导的胶原凝胶收缩的性别依赖性敏感性（女性>男性；p=0.025）和性别依赖性增殖反应（女性>男性；p<0.001），这在腹部VSMC中并不明显。尽管原发性VSMC在生物学反应中表现出内在区域和性别差异，这可能与CVD表现有关。炎症和性激素等几个因素未纳入本研究.此类因素应包括在与男性和女性CVD差异相关的体外机械生物学反应的未来研究中。
