Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr Al-Aini Street, Cairo 11562, Egypt.
Department of Anesthesiology, Faculty of Medicine, Pharmacology and Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Int J Mol Sci. 2020 Aug 26;21(17):6147. doi: 10.3390/ijms21176147.
The variable nature of vascular dysfunction in diabetes is not well understood. We explored the functional adaptation of different arteries in mice in relation to increased severity and duration of diabetes. We compared endothelium-dependent and -independent vasodilation in the aortae, as well as the carotid and femoral arteries, of mice at three ages in parallel with increased body weight, oxidative stress, and deterioration of glycemic control. Vascular responses to in vitro generation of reactive oxygen species (ROS) and expression of superoxide dismutase (SOD) isoforms were assessed. There was a progressive impairment of endothelium-dependent and -independent vasorelaxation in the aortae of mice. The carotid artery was resistant to the effects of and in vitro induced oxidative stress, and it maintained unaltered vasodilatory responses, likely because the carotid artery relaxed in response to ROS. The femoral artery was more reliant on dilation mediated by endothelium-dependent hyperpolarizing factor(s), which was reduced in mice at the earliest age examined and did not deteriorate with age. Substantial heterogeneity exists between the three arteries in signaling pathways and protein expression of SODs under physiological and diabetic conditions. A better understanding of vascular heterogeneity will help develop novel therapeutic approaches for targeted vascular treatments, including blood vessel replacement.
血管功能障碍在糖尿病中的多变性尚不清楚。我们研究了不同动脉在与糖尿病严重程度和持续时间增加相关的情况下的功能适应性。我们比较了不同年龄的 小鼠的主动脉、颈动脉和股动脉的内皮依赖性和非依赖性血管舒张，并平行研究了体重增加、氧化应激和血糖控制恶化。评估了体外产生的活性氧 (ROS) 和超氧化物歧化酶 (SOD) 同工型表达对血管反应的影响。 小鼠的主动脉内皮依赖性和非依赖性血管舒张功能逐渐受损。颈动脉对 和体外诱导的氧化应激的作用具有抗性，并且其舒张反应保持不变，这可能是因为颈动脉对 ROS 产生反应而舒张。股动脉更依赖于内皮依赖性超极化因子介导的舒张，而在最早检查的年龄的 小鼠中，这种舒张减少，并且不会随年龄恶化。在生理和糖尿病条件下，三种动脉之间的信号通路和 SOD 蛋白表达存在明显的异质性。更好地了解血管异质性将有助于开发针对血管治疗的新型治疗方法，包括血管替代。
