Cardiovascular Health Research Center, Sanford Research/University of South Dakota, Sioux Falls, South Dakota, United States of America.
PLoS One. 2011;6(9):e25054. doi: 10.1371/journal.pone.0025054. Epub 2011 Sep 22.
Low thyroid hormone (TH) function has been linked to impaired coronary blood flow, reduced density of small arterioles, and heart failure. Nonetheless, little is known about the mechanisms by which THs regulate coronary microvascular remodeling. The current study examined the initial cellular events associated with coronary remodeling induced by triiodothyronine (T3) in hypothyroid rats. Rats with established hypothyroidism, eight weeks after surgical thyroidectomy (TX), were treated with T3 for 36 or 72 hours. The early effects of T3 treatment on coronary microvasculature were examined morphometrically. Gene expression changes in the heart were assessed by quantitative PCR Array. Hypothyroidism resulted in arteriolar atrophy in the left ventricle. T3 treatment rapidly induced small arteriolar muscularization and, within 72 hours, restored arteriolar density to control levels. Total length of the capillary network was not affected by TX or T3 treatment. T3 treatment resulted in the coordinate regulation of Angiopoietin 1 and 2 expression. The response of Angiopoietins was consistent with vessel enlargement. In addition to the well known effects of THs on vasoreactivity, these results suggest that THs may affect function of small resistance arteries by phenotypic remodeling of vascular smooth muscle cells (VSMC).
甲状腺激素(TH)功能低下与冠状动脉血流受损、小动脉密度降低和心力衰竭有关。尽管如此,关于 TH 调节冠状动脉微血管重塑的机制知之甚少。本研究探讨了三碘甲状腺原氨酸(T3)在甲状腺功能减退大鼠中诱导冠状动脉重塑的初始细胞事件。甲状腺切除术(TX) 8 周后建立甲状腺功能减退的大鼠,用 T3 治疗 36 或 72 小时。通过形态计量学检查 T3 治疗对冠状动脉微血管的早期影响。通过定量 PCR 阵列评估心脏中的基因表达变化。甲状腺功能减退导致左心室小动脉萎缩。T3 治疗迅速诱导小动脉肌化,72 小时内将小动脉密度恢复到对照水平。毛细血管网络的总长度不受 TX 或 T3 治疗的影响。T3 治疗导致血管生成素 1 和 2 的表达协调调节。血管生成素的反应与血管扩张一致。除了 TH 对血管反应性的众所周知的影响外,这些结果表明 TH 可能通过血管平滑肌细胞(VSMC)的表型重塑来影响小阻力动脉的功能。