Harnoss Jonathan M, Krackhardt Florian, Ritter Zully, Granzow Susanne, Felsenberg Dieter, Neumann Konrad, Lerman Lilach O, Riediger Fabian, Hillmeister Philipp, Bramlage Peter, Buschmann Ivo R
Department for Angiology, Center for Internal Medicine I, Medizinische Hochschule Brandenburg (MHB), Brandenburg Medical School, Hochstr. 29, 14770, Brandenburg, Germany.
Department of Cardiology, Charité University Hospital, Campus Virchow, Berlin, Germany.
Heart Vessels. 2017 Nov;32(11):1400-1409. doi: 10.1007/s00380-017-1028-x. Epub 2017 Aug 3.
Bridging collaterals (BC) develop in several chronic total artery occlusion diseases, and can prevent extensive myocardial necrosis. Yet, their origin, growth process, and histo-morphology are still unclear. Since vasa vasorum (VV) may take part in collateralization, we hypothesized that VV are the basis for BCs. To comprehensively investigate this arteriogenesis process, we used high-resolution imaging, including corrosion casts, post-mortem angiography with stereoscopy, micro-CT, and immunohistology, in combination with a novel semi-acute vessel occlusion model. This porcine model was produced by implanting a copper stent minimally invasively into the left anterior descending coronary artery. To define the kinetics of arteriogenesis, pigs (n = 11) were assigned to one of the five euthanasia timepoints: day 0.5 (D0.5, n = 2), D3 (n = 2), D5 (n = 1), D7 (n = 3), or D12 (n = 3) after stent implantation. We found that (1) BCs originate from longitudinally running type 1 VV, mainly VV interna, partially also from VV externa; (2) the growth of VV to BC is rapid, occurring within 7 days; and (3) porcine BCs are likely functionally relevant, considering an observed 102% increase in the number of smooth muscle cell layers in their vascular wall. High-resolution imaging in a minimally invasive non-acute vessel occlusion model is an innovative technique that allowed us to provide direct evidence that porcine BCs develop from the VV. These data may be crucial for further studies on the treatment of angina pectoris and thromboangiitis obliterans through therapeutic stimulation of BC development.
桥接侧支血管（BC）在多种慢性冠状动脉完全闭塞性疾病中形成，并可预防广泛的心肌坏死。然而，它们的起源、生长过程和组织形态仍不清楚。由于血管滋养管（VV）可能参与侧支循环形成，我们推测VV是BC的基础。为了全面研究这一动脉生成过程，我们使用了高分辨率成像技术，包括铸型腐蚀、立体尸检血管造影、微型计算机断层扫描（micro-CT）和免疫组织学，并结合一种新型的半急性血管闭塞模型。该猪模型是通过将铜支架微创植入左前降支冠状动脉而制成的。为了确定动脉生成的动力学，将猪（n = 11）分配到五个安乐死时间点之一：支架植入后第0.5天（D0.5，n = 2）、第3天（D3，n = 2）、第5天（D5，n = 1）、第7天（D7，n = 3）或第12天（D12，n = 3）。我们发现：（1）BC起源于纵向走行的1型VV，主要是VV interna，部分也来自VV externa；（2）VV向BC的生长迅速，在7天内发生；（3）考虑到观察到猪BC血管壁平滑肌细胞层数增加102%，其可能具有功能相关性。在微创非急性血管闭塞模型中进行高分辨率成像，是一项创新技术，使我们能够提供直接证据，证明猪BC由VV发育而来。这些数据对于进一步研究通过治疗性刺激BC发育来治疗心绞痛和血栓闭塞性脉管炎可能至关重要。
