Sahlgrenska Center for Cardiovascular and Metabolic Research, Institute of Medicine, the Sahlgrenska Academy at the University of Gothenburg and Wallenberg Laboratory, Gothenburg, Sweden.
J Vasc Surg. 2011 Nov;54(5):1324-1331.e5. doi: 10.1016/j.jvs.2011.04.061. Epub 2011 Jul 20.
Increased vascularization is considered an important contributing factor for plaque vulnerability. Microvascular proliferative disease in patients with diabetes results in renal damage and visual loss. We assessed the hypothesis that vascularization in carotid atherosclerotic tissue is increased in diabetic patients, especially in the critical shoulder regions of the plaque.
Carotid endarterectomy specimens, clinical data, and blood samples were collected from patients with symptomatic carotid artery stenosis (median 85 days after clinical event) and pharmacologic treatment for diabetes (n = 26) or no diabetes (n = 85). Plaques were fixed in formalin and transverse tissue sections prepared. Histopathology and immunohistochemistry were performed for detection of endothelial cells (anti-CD34), macrophages (anti-CD68), vascular endothelial growth factor (VEGF), and its receptor (VEGFR-2). Neovascularization was assessed as CD34(+) neovessel density in the entire section area and by the presence or absence of CD34(+) vessels in the shoulder and cap regions of the plaques.
The patient groups did not differ significantly in neovascularization in the entire transverse sections (2.0 vs 2.1 vessels/mm(2); P = .61) or in the fibrous cap (52% of the patients in both groups; P = .95). Neovascularization of the plaque shoulder regions was observed in 52% of the diabetic patients and in 26% of the nondiabetic patients (P = .028). VEGF-stained areas were similar in the two patient groups (0.4% and 0.2% of shoulder area; P = .61). Patients with diabetes had more VEGFR-2 (1.0% vs 0.2% of shoulder area; P < .016) and less CD68 staining (0.4% vs 3.6% of shoulder area; P < .008). Time from clinical event to surgery was positively associated with neovascularization of the plaque shoulder regions (≤90 days, 18% of patients; >90 days, 50% of patients; P = .002), independently of diabetes status.
Diabetes was associated with increased vascularization of the shoulder regions in patients with symptomatic carotid atherosclerotic plaques. This was accompanied by increased expression of VEGFR-2. The increased vascularization of the plaque shoulder regions may help explain why patients with diabetes are at increased risk of atherosclerotic complications.
血管生成增加被认为是斑块易损性的一个重要影响因素。糖尿病患者的微血管增生性疾病可导致肾脏损害和视力丧失。我们评估了以下假说，即颈动脉粥样硬化组织中的血管生成在糖尿病患者中增加，尤其是在斑块的关键肩部区域。
收集有症状颈动脉狭窄患者（临床事件后中位数 85 天）的颈动脉内膜切除术标本、临床数据和血样，以及接受药物治疗的糖尿病患者（n = 26）或无糖尿病患者（n = 85）。将斑块固定在福尔马林中，并制备横向组织切片。进行组织病理学和免疫组织化学检测，以检测内皮细胞（抗-CD34）、巨噬细胞（抗-CD68）、血管内皮生长因子（VEGF）及其受体（VEGFR-2）。通过在整个切片区域检测 CD34（+）新生血管密度和检测斑块肩部和帽部区域是否存在 CD34（+）血管来评估新生血管形成。
两组患者在整个横切面上的新生血管形成（2.0 与 2.1 个血管/mm²；P =.61）或纤维帽（两组各有 52%的患者；P =.95）均无显著差异。在 52%的糖尿病患者和 26%的非糖尿病患者中观察到斑块肩部区域的新生血管形成（P =.028）。两组患者的 VEGF 染色区域相似（肩部区域的 0.4%和 0.2%；P =.61）。糖尿病患者的 VEGFR-2 较多（肩部区域的 1.0%与 0.2%；P <.016），CD68 染色较少（肩部区域的 0.4%与 3.6%；P <.008）。从临床事件到手术的时间与斑块肩部区域的新生血管形成呈正相关（≤90 天，18%的患者；>90 天，50%的患者；P =.002），独立于糖尿病状态。
在有症状的颈动脉粥样硬化斑块患者中，糖尿病与斑块肩部区域的血管生成增加有关。这伴随着 VEGFR-2 的表达增加。斑块肩部区域的血管生成增加可能有助于解释为什么糖尿病患者患动脉粥样硬化并发症的风险增加。
