Fu Yuyang, Duru Enrico A, Davies Mark G
Vascular Biology and Therapeutics Program, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, Texas; Department of Cardiovascular Surgery, Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, Texas.
Vascular Biology and Therapeutics Program, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, Texas; Department of Cardiovascular Surgery, Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, Texas.
J Surg Res. 2014 Sep;191(1):33-41. doi: 10.1016/j.jss.2014.05.051. Epub 2014 May 27.
Metabolic syndrome is now an epidemic in the United States population. Intimal hyperplasia remains the principal lesion in the development of restenosis after vessel wall injury. The aim of this study is to characterize the changes induced in wall morphology in the developing intimal hyperplasia within a murine model in the presence of diabetes (type 1) and metabolic syndrome.
Control (wild type B6), Non Obese Diabetic, and metabolic syndrome (RCS-10) mice were used. The murine femoral wire injury model was used in which a micro wire is passed through a branch of the femoral and used to denude the common femoral and iliac arteries. Specimens were perfusion fixed and sections were stained with hematoxylin and eosin and Movat stains such that dimensional and compositional morphometry could be performed using an ImagePro system. Additional stains for proliferation and apoptosis were used.
In control mice, the injured femoral arteries develop intimal hyperplasia, which is maximal at 28 d and remains stable to day 56. Sham-operated vessels do not produce such a response. In diabetic mice, the intimal response increased 5-fold with a 2-fold increase in proteoglycan deposition, whereas in the metabolic syndrome mice there was a 6-fold increase in the intimal response and a similar increase in proteoglycan deposition. Collagen deposition was different with a 22-fold increase over control in collagen deposition in diabetes and a 100-fold increase over control in collagen deposition in metabolic syndrome as compared with the control injury mice. Maximal vascular smooth muscle cell (VSMC) proliferation was decreased in both diabetes and metabolic syndrome compared with controls, whereas early cell apoptosis in both diabetes and metabolic syndrome was sustained over a longer period of time compared with wild-type mice.
These data demonstrate that development of intimal hyperplasia is markedly different in diabetes and metabolic syndrome compared with controls, with an increase in collagen deposition, a reduction in VSMC proliferation, and an increase in early VSMC apoptosis. These findings suggest that preventative strategies against restenosis must be tailored for the diabetic and metabolic syndrome patients.
代谢综合征目前在美国人群中呈流行态势。内膜增生仍是血管壁损伤后再狭窄发展过程中的主要病变。本研究的目的是在存在糖尿病（1型）和代谢综合征的小鼠模型中，描述正在形成的内膜增生过程中血管壁形态的变化。
使用对照（野生型B6）、非肥胖糖尿病和代谢综合征（RCS - 10）小鼠。采用小鼠股动脉钢丝损伤模型，将一根微钢丝穿过股动脉的一个分支，用于剥脱股总动脉和髂动脉。标本经灌注固定，切片用苏木精和伊红以及莫瓦特染色，以便使用ImagePro系统进行尺寸和成分形态测量。还使用了增殖和凋亡的额外染色。
在对照小鼠中，受损的股动脉会发生内膜增生，在28天时达到最大值，并在第56天保持稳定。假手术的血管不会产生这种反应。在糖尿病小鼠中，内膜反应增加了5倍，蛋白聚糖沉积增加了2倍，而在代谢综合征小鼠中，内膜反应增加了6倍，蛋白聚糖沉积也有类似增加。胶原沉积有所不同，与对照损伤小鼠相比，糖尿病小鼠的胶原沉积比对照增加了22倍，代谢综合征小鼠的胶原沉积比对照增加了100倍。与对照相比，糖尿病和代谢综合征小鼠的最大血管平滑肌细胞（VSMC）增殖均降低，而与野生型小鼠相比，糖尿病和代谢综合征小鼠的早期细胞凋亡持续时间更长。
这些数据表明，与对照相比，糖尿病和代谢综合征中内膜增生的发展明显不同，胶原沉积增加，VSMC增殖减少，早期VSMC凋亡增加。这些发现表明，针对再狭窄的预防策略必须针对糖尿病和代谢综合征患者量身定制。
