UNASSIGNED: Diabetes was induced by streptozotocin (STZ) injections (n = 7-11 animals in each group) in Tenascin C KO (TNC KO) mice and their Wild type (A/J) littermates. After 16-18 weeks the heart was removed and the whole subsurface network of the left coronary artery was prepared (down to branches of 40 μ m outer diameter), in situ pressure-perfused and studied using video-microscopy. Outer and inner diameters, wall thicknesses and bifurcation angles were measured on whole network pictures reconstructed into collages at 1.7 μ m pixel resolutions.
UNASSIGNED: Diabetes induced abnormal morphological alterations including trifurcations, sharp bends of larger branches, and branches directed retrogradely (p < 0.001 by the χ 2 test). Networks of TNC KO mice tended to form early divisions producing parallelly running larger branches (p < 0.001 by the χ 2 probe). Networks of coronary resistance arteries were substantially more abundant in 100-180 μ m components, appearing in 2-5 mm flow distance from orifice in diabetes. This was accompanied by thickening of the wall of larger arterioles ( > 220 μ m) and thinning of the wall of smaller (100-140 μ m) arterioles (p < 0.001). Blood flow should cover larger distances in diabetic networks, but interestingly STZ-induced diabetes did not generate further geometrical changes in TNC KO mice.
UNASSIGNED: Diabetes promotes hypertrophic and hypotrophic vascular remodeling and induces vasculogenesis at well defined, specific positions of the coronary vasculature. TNC plays a pivotal role in the formation of coronary network geometry, and TNC deletion causes parallel fragmentation preventing diabetes-induced abnormal vascular morphologies.
在生腱蛋白CKO(TNCKO)小鼠及其野生型(A/J)同窝猫中通过链脲佐菌素(STZ)注射(每组n=7-11只动物)诱导糖尿病。16-18周后,取出心脏,制备左冠状动脉的整个地下网络(直到外径为40μm的分支),原位压力灌注和使用视频显微镜研究。外径和内径,在以1.7μm像素分辨率重建成拼贴的整个网络图片上测量壁厚和分叉角。
■糖尿病引起的异常形态学改变,包括三叉根,较大树枝的急弯,和分支逆行(χ2检验p<0.001)。TNCKO小鼠的网络倾向于形成早期分裂,产生平行运行的较大分支(χ2探针p<0.001)。冠状动脉阻力动脉网络在100-180μm成分中基本上更丰富,出现在2-5毫米的流量距离从孔口在糖尿病。这伴随着较大小动脉壁的增厚(>220μm)和较小(100-140μm)小动脉壁的变薄(p<0.001)。在糖尿病网络中,血流应该覆盖更大的距离,但有趣的是,STZ诱导的糖尿病在TNCKO小鼠中没有产生进一步的几何学变化。
■糖尿病促进肥厚性和低肥厚性血管重塑,并在明确定义的情况下诱导血管生成,冠状动脉血管的特定位置。TNC在冠状动脉网络几何形状的形成中起着关键作用,和TNC缺失导致平行片段化,防止糖尿病诱导的异常血管形态。