Beck Lilliana, Su Junjing, Comerma-Steffensen Simon, Pinilla Estéfano, Carlsson Rune, Hernanz Raquel, Sheykhzade Majid, Danielsen Carl Christian, Simonsen Ulf
Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Faculty of Health Aarhus University, Aarhus, Denmark.
Department of Biomedical Sciences/Animal Physiology, Veterinary Faculty, Central University of Venezuela, Maracay, Venezuela.
Front Physiol. 2020 Jun 23;11:667. doi: 10.3389/fphys.2020.00667. eCollection 2020.
Endothelial cell dysfunction and vessel stiffening are associated with a worsened prognosis in diabetic patients with cardiovascular diseases. The present study hypothesized that sex impacts endothelial dysfunction and structural changes in arteries from diabetic mice. In diabetic (db/db) and normoglycaemic (db/db+) mice, the mechanical properties were investigated in pressurized isolated left anterior descending coronary arteries and aorta segments that were subjected to tensile testing. Functional studies were performed on wire-mounted vascular segments. The male and female db/db mice were hyperglycaemic and had markedly increased body weight. In isolated aorta segments without the contribution of smooth muscle cells, load to rupture, viscoelasticity, and collagen content were decreased suggesting larger distensibility of the arterial wall in both male and female db/db mice. In male db/db aorta segments with smooth muscle cell contribution, lumen diameter was smaller and the passive stretch-tension curve was leftward-shifted, while they were unaltered in female db/db aorta segments versus control db/db+ mice. In contrast to female db/db mice, coronary arteries from male db/db mice had altered stress-strain relationships and increased distensibility. Transthoracic echocardiography revealed a dilated left ventricle with unaltered cardiac output, while aortic flow velocity was decreased in male db/db mice. Impairment of acetylcholine relaxation was aggravated in aorta from female db/db compared to control and male db/db mice, while impairment of sodium nitroprusside relaxations was only observed in aorta from male db/db mice. The remodeling in the coronary arteries and aorta suggests an adaptation of the arterial wall to the reduced flow velocity with sex-specific differences in the passive properties of aorta and coronary arteries. The findings of less distensible arteries and more pronounced endothelial dysfunction in female compared to male diabetic mice may have implications for the observed higher incidence of macrovascular complications in diabetic women.
内皮细胞功能障碍和血管硬化与糖尿病心血管疾病患者预后恶化相关。本研究假设性别会影响糖尿病小鼠动脉的内皮功能障碍和结构变化。在糖尿病（db/db）和血糖正常（db/db+）小鼠中，对加压分离的左前降支冠状动脉和主动脉段进行拉伸试验，研究其力学性能。对安装在金属丝上的血管段进行功能研究。雄性和雌性db/db小鼠均出现高血糖且体重显著增加。在无平滑肌细胞影响的分离主动脉段中，破裂负荷、粘弹性和胶原蛋白含量降低，表明雄性和雌性db/db小鼠的动脉壁扩张性更大。在有平滑肌细胞影响的雄性db/db主动脉段中，管腔直径较小，被动拉伸-张力曲线向左移位，而雌性db/db主动脉段与对照db/db+小鼠相比则无变化。与雌性db/db小鼠不同，雄性db/db小鼠的冠状动脉应力-应变关系改变，扩张性增加。经胸超声心动图显示左心室扩张，心输出量未改变，而雄性db/db小鼠的主动脉流速降低。与对照和雄性db/db小鼠相比，雌性db/db小鼠主动脉中乙酰胆碱舒张功能的损害更为严重，而仅在雄性db/db小鼠的主动脉中观察到硝普钠舒张功能的损害。冠状动脉和主动脉的重塑表明动脉壁适应了流速降低，且主动脉和冠状动脉的被动特性存在性别差异。与雄性糖尿病小鼠相比，雌性糖尿病小鼠动脉扩张性较小且内皮功能障碍更明显，这一发现可能解释了糖尿病女性大血管并发症发生率较高的现象。
