应用光学相干断层成像对老年与中青年颈动脉粥样硬化性斑块特征的分析

目的 应用光学相干断层成像(OCT)评价老年与中青年患者颈动脉粥样硬化性斑块特征的区别.方法 回顾性连续纳入2017年6月至2021年2月在东部战区总医院神经内科完成颈动脉OCT检查的颈动脉粥样硬化性狭窄患者86例,分别将年龄<60岁、年龄≥60岁患者分为中青年组(17例,占19.8％)和老年组(69例,占80.2％)...     

影像学检查对缺血性脑血管病患者颈动脉粥样硬化斑块的研究

目的采用双源CT血管造影(CTA)和高分辨MRI,探讨缺血性脑血管病患者颈总动脉分叉处粥样硬化斑块的性质、成分和动脉管腔狭窄程度与缺血性脑血管病的关系。方法选择缺血性脑血管病患者40例,经颈部CTA检测出颈总动脉分叉处粥样硬化斑块并伴管腔狭窄,再接受MRI扫描;分析颈动脉粥样斑块的性质、成分及管腔狭窄程度。结果 40例患者中,CTA检出斑块61个,其中混合性斑块31个;钙化性斑块18个;软斑块12个。高血压30例,检出斑块49个;无高血压10例,检出斑块12个。MRI检出斑块61个,其中Ⅲ型14个;Ⅳ～Ⅴ型23个,Ⅵ型6个;Ⅶ型18个。斑块内溃疡6例;颈动脉粥样硬化斑块造成同侧急性脑梗死14例,双侧颈动脉斑块造成双侧脑梗死10例,一侧颈动脉检出粥样斑块而对侧发生脑梗死2例。结论缺血性脑血管病患者颈动脉粥样硬化斑块主要以混合性斑块为主,双侧好发;高血压患者斑块发生率高于无高血压患者;颈动脉粥样硬化斑块造成同侧脑梗死发生率较高。     

颈动脉粥样硬化斑块成分与性别的相关性研究

目的探讨颈动脉粥样硬化患者斑块成分的性别差异。方法选取进行颈动脉3.0T MR高分辨扫描的颈动脉粥样硬化斑块患者154例,男性95例,女性59例,根据MR扫描结果,对斑块成分和性质进行分析,比较男、女性的斑块成分差异。结果男性斑块内富脂质坏死核(42.1%vs 20.0%,P=0.005)和薄或破裂纤维帽(59.7%vs39.5%,P=0.046)的发生率明显高于女性;女性斑块内钙化的发生率有高于男性的趋势(74.6%vs 65.3%,P=0.225),男性与女性斑块内出血发生率比较,差异无统计学意义(24.2%vs 22.0%,P=0.756)。结论颈动脉粥样硬化斑块患者中,男性不稳定斑块的发生率高于女性,这可能有助于解释脑卒中发病率的性别差异。     

Low thrombogenicity of calcified atherosclerotic plaques is associated with bone morphogenetic protein-2-dependent inhibition of tissue factor expression

Morphology of atherosclerotic plaque is a major determinant of plaque thrombogenicity. Calcified atherosclerotic lesions are less prone to thrombosis and contain less tissue factor (TF) than lipid-rich plaques. Although bone morphogenetic protein (BMP)-2 is a known mediator of vascular calcification, the role of BMP-2 in the regulation of plaque thrombogenicity has not been established. We hypothesized that the expression of BMP-2 within highly calcified atherosclerotic plaques inhibits TF expression and reduces thrombogenicity of calcified lesions. In the present study, we measured levels of TF and BMP-2 in human calcified and lipid-rich carotid plaques and studied the effects of BMP-2 on TF expression in human monocytes in vitro. Quantitative immunohistochemical analysis of endarterectomy specimens for TF and BMP-2 revealed that calcified plaques contained nearly three-times less TF antigen than lipid-rich ones. In contrast, calcified plaques expressed two-times more BMP-2 antigen than lipid-rich lesions. BMP-2 markedly decreased protein expression and surface redistribution of TF in activated human monocytes in vitro. BMP-2-mediated inhibition of TF expression in monocytes/macrophages could contribute to reduced thrombogenicity of calcified atherosclerotic plaques.     

Atherosclerotic carotid arteries - calcification and radio-morphological findings

Summary Objectives: Are there any predictable factors influencing the process of calcification in carotid arteries? Background: The carotid arteries and especially the carotid bifurcation are one of the predisposed regions of atherosclerotic disease. Whether topography of the carotid sinus, flow patterns or different patient characteristics (e.g., diabetes mellitus, age, sex) are a factor determining calcification of atherosclerotic lesion is still hardly understood. Methods: Morphological and morphometrical analysis including radiographic classification of different degrees of calcification on postmortal carotid arteries (90 men and 19 women) and 306 surgical samples after intramural desobliterations of carotid arteries 202 patients with diabetes, 104 patients without diabetes). Results. Most common localization of radiographically identified calcified deposits are the carotid bulb (76%) especially on the lateral wall opposite the flow divider and the internal carotid artery (55%) especially the proximal 1 cm section. No difference in degree of calcification was found when comparing patients with and without diabetes (intermediate calcification in 59% of patients with diabetes and 50% without diabetes). More female patients with diabetes show calcification when compared to the group of patients without diabetes. Females produce calcification in atherosclerotic carotid lesions at an older age compared to male patients. Conclusions: Calcification is a frequent finding in advanced atherosclerotic carotid lesions. There is no difference in regard to degree, pattern of calcification or age distribution when comparing patients with and without diabetes mellitus. Atherosclerotic lesions more frequently found in female patients with diabetes may be due to less vasoprotection by estrogenes.     

Contrast enhancement of coronary atherosclerotic plaque: a high-resolution, multidetector-row computed tomography study of pressure-perfused, human ex-vivo coronary arteries

OBJECTIVES: The objective of this study was to investigate the effect of contrast injection on atherosclerotic coronary plaque attenuation measured using multidetector-row computed tomography. BACKGROUND: Recent multidetector-row computed tomography studies have described the characterization of coronary atherosclerotic plaque on the basis of Hounsfield unit values. The influence of contrast injection on the attenuation of individual plaque components, however, is unknown. METHODS: Using a pressurized perfusion system, 10 human coronary arteries were examined postmortem with multidetector-row computed tomography and histology. Pre-enhanced, peak-enhanced, and delayed enhanced multidetector-row computed tomography images were acquired during continuous perfusion of the vessel. A total of 37 focal atherosclerotic plaques were identified. Vessel wall attenuation was measured from multidetector-row computed tomography images during all three enhancement phases. On the basis of the histology, plaques were categorized as noncalcified (predominantly fibrous or predominantly fibrofatty), mixed calcified (calcified fibrous or calcified necrotic core), or densely calcified. The mean Hounsfield unit was compared among contrast phases for all plaques and in plaque subgroups. RESULTS: We observed contrast enhancement of atherosclerotic plaques within the vessel wall. For noncalcified plaques including both fibrous and fibrofatty plaques, the mean Hounsfield unit of the vessel wall during and after contrast injection exceeded the mean value before injection (t-test, P<0.002). CONCLUSION: The present study demonstrates that intra-arterial injection of iodinated contrast agent results not only in luminal enhancement but also in atherosclerotic plaque enhancement in pressure-perfused coronary arteries imaged ex vivo. Plaque enhancement should be considered when characterizing plaque components on the basis of Hounsfield unit with multidetector-row computed tomography.     

联合应用无创影像学技术预警颈动脉不稳定斑块的相关研究

目的应用高分辨率动态对比增强磁共振成像(DCE-MRI),正电子发射断层显像(PET)技术检测患者颈动脉粥样硬化斑块,比较不同斑块成分之间的炎性程度,为早期预警颈动脉粥样硬化提供临床依据。方法选取颈动脉超声下斑块厚度>2mm的患者41例,分别行DCE-MRI和PET检查。以DCE-MRI图像分析结果,依照粥样硬化斑块表面纤维帽(无纤维帽、厚纤维帽、薄纤维帽、纤维帽破裂)或斑块内血管成分(钙化、胶原、脂质、出血),分析不同斑块性质影像学区别。以DCE-MRI为向导标记PET斑块位置,计算局部放射性活度标准化靶-本底比值(TBR),将DCE-MRI及PET对比研究,比较不同成分斑块间炎性反应程度,以鉴别不稳定斑块。结果不同斑块表面纤维帽中:纤维帽破裂TBRmax值最高,无纤维帽TBRmax值最低,两者比较差异有统计学意义(P<0.01);不同斑块成分中TBRmax值由大到小排列为:斑块出血、富含脂质坏死核、斑块胶原、斑块钙化,除斑块胶原与斑块钙化比较无显著差异外,其他斑块血管成分间差异均有统计学意义(P<0.01)。结论 DCE-MRI和PET无创检查技术联合应用,可以用于颈动脉粥样硬化的早期诊断与评估。     

Atherosclerotic plaques composed of a large core of foam cells covered with thin fibrous caps in twice-injured carotid arterial specimens obtained from high cholesterol diet-fed rabbits.

We attempted to find atherosclerotic plaques including a large lipid core and thin fibrous cap in twice-injured arterial specimens obtained from high cholesterol diet (HCD) fed rabbits. Rabbits fed a HCD were subjected to carotid artery injury using a balloon catheter. After 2 or 4 weeks of cholesterol feeding, a second mild injury was induced in the same region as the first injury. The rabbits were given a standard diet for 2 weeks after the second injury. Typical atherosclerotic plaques with a fibrous cap formed by smooth muscle cells and extracellular matrix overlying a core formed by macrophage foam cells were observed in the lesion. Gelatin proteolytic activities were found in homogenates containing either media or intima from the injured artery, and activated matrix metalloproteinase-2 (MMP2) was detected. With prolongation of the HCD feeding period (interval between injuries) from 2 weeks to 4 weeks, typical plaque was observed more frequently. Furthermore, the neointimal area and the macrophage foam cells area increased, as did gelatin-proteolytic activity. Since the typical atherosclerotic plaques observed in the present study have some histopathological and pathogenic characteristics in common with unstable atherosclerotic plaque, we expect that the typical atherosclerotic plaque found in the present study will be useful for basic studies of plaque stabilization and prevention of acute coronary syndromes.     

冠心病患者外周血细胞外基质金属蛋白酶诱导因子表达量与斑块特征相关性分析

目的 分析冠状动脉粥样硬化性心脏病(冠心病)患者外周血细胞外基质金属蛋白酶诱导因子(EMMPRIN)表达量与斑块特征的相关性.方法 选取2017年6月至2019年6月于山东第一医科大学附属济南人民医院心内科就诊的急性冠脉综合征患者(ACS组)82例和稳定型心绞痛患者(SAP组)57例作为研究对象,另选取同期于体检的健康...     

Velocity Vector Imaging of Longitudinal Mechanical Properties of Upstream and Downstream Shoulders and Fibrous Cap Tops of Human Carotid Atherosclerotic Plaque

Aims: Atherosclerotic plaque rupture is closely related to high regional mechanical stress in the plaque itself. We aimed to explore the longitudinal mechanical properties of upstream and downstream shoulders and fibrous cap tops of human atherosclerotic plaques in vivo by velocity vector imaging (VVI) combined with acoustic densitometry (AD) imaging. Methods and Results: We included 135 patients with carotid atherosclerotic plaque. VVI and AD were used to examine 3 regions of carotid plaque along the longitudinal‐axis view. A total of 405 regions were classified with low or high AD values by corrected averages image intensity (AIIc%) < or ≥50, respectively. Peak systolic strain, strain rate (SR), and velocity were significantly greater for upstream than downstream shoulders and fibrous cap tops of carotid plaque (P < 0.05 for both). AIIc% was significantly lower for upstream than downstream plaque shoulders (P < 0.05). Peak systolic SR of the plaque regions was negatively correlated with corresponding AIIc% (R² = 0.499, P < 0.05). Conclusions: The longitudinal strain of human carotid atherosclerotic plaques as derived by VVI is associated with its corresponding AD but also in part with the internal position of the strain, with values greater for upstream than downstream shoulders and fibrous cap tops.     

颈动脉粥样硬化斑块性质与颅内血流动力学变化的相关性

目的利用16排螺旋CT血管成像及灌注成像探讨颈动脉粥样硬化斑块性质与颅内血流动力学的相关性。方法对42例颈动脉超声证实的颈动脉斑块患者行16排螺旋CT灌注成像-血管成像检查,根据CT值的不同分析斑块成分,并将脂肪斑块和纤维斑块定义为不稳定性斑块,钙化斑块定义为稳定性斑块;利用灌注成像分析颅内脑血流灌注情况。结果42例颈动脉斑块患者中不稳定性斑块25例,其中脂肪斑块10例,纤维斑块15例;稳定性斑块17例。14例表现为症状相应区域低灌注,其中脂肪斑块颅内低灌注的发生率为70%,纤维斑块颅内低灌注的发生率为47%,而钙化斑块无颅内低灌注表现。结论不稳定性斑块的存在比较稳定性斑块易于引起颅内血流动力学变化。     

Increased levels of the homeostatic chemokine CXCL13 in human atherosclerosis - Potential role in plaque stabilization

ObjectivesBased on the newly recognized role of the homeostatic chemokines in inflammation, we hypothesized that CXCL13 could modulate atherogenesis and plaque destabilization.MethodsThe study included in vivo analyses in patients with carotid atherosclerosis and in vitro experiments in cells involved in atherogenesis (ie, monocytes/macrophages, vascular smooth muscle cells [SMC], and platelets).ResultsOur main findings were: (i) Patients with carotid atherosclerosis (n = 130) had increased plasma levels of CXCL13 with particularly high levels in symptomatic disease. (ii) CXCL13 showed increased expression within atherosclerotic carotid plaques as compared with non-atherosclerotic vessels. (iii) Within the atherosclerotic lesions, CXCR5 and CXCL13 were expressed by macrophages and SMC in all stages of plaque progression. (iv) Releasate from activated platelets and toll-like receptor activation enhanced the expression of CXCL13 in THP-1 monocytes and primary monocytes. (v) In vitro, CXCL13 exerted anti-apoptotic effects in primary monocytes, THP-1 macrophages, and vascular SMC. (vi) CXCL13 increased arginase-1, transforming growth factor-β, and interleukin-10 expression in THP-1 cells and in samples from isolated carotid plaques.ConclusionLevels of CXCL13 are increased in carotid atherosclerosis both systemically and within the atherosclerotic lesion. Based on our in vitro findings, we hypothesize a potential plaque stabilizing effects of CXCL13-CXCR5 interaction.     

Plaque calcification is driven by different mechanisms of mineralization associated with specific cardiovascular risk factors

Background and aimsThe aim of this study was to investigate possible associations among markers of mineralization, plaque instability and the main risk factors of atherosclerosis.Methods and resultsA Tissue MicroArray containing 52 samples of calcified carotid plaques from 52 symptomatic and asymptomatic patients were built. TMA serial sections were used to study the expression of inflammatory and mineralization markers (BMP-2, BMP-4, VDR, RANKL, Osteopontin, Sclerostin, β-catenin and calmodulin) by immunohistochemistry. Our data clearly demonstrated the expression of mineralization markers in atheromatic plaques. Indeed, with the exception of RANKL, all investigated markers were expressed in at least 60% of cases. Specifically, multivariate analysis displayed significant associations between both the expression of BMP-2 and the presence of unstable plaques as well as between the expression of β-catenin and the presence of stable plaques. We also found a significant inverse association between both a) the presence of hypertension and VDR and b) smoking habits and calmodulin expression. Finally, we noted a higher density of RANKL positive cells in plaques from diabetic patients as compared to non-diabetic ones and a significant positive association between hypertriglyceridemia and BMP-4 expression.ConclusionOur results support the hypothesis that the process of atherosclerotic plaque calcification presents a number of similarities with the physiological processes that occur in bone, involving both osteoblasts- and osteoclasts-like arterial cells. Finally, the present study suggests that risk factors, such as hypertension, cigarette smoke and diabetes, can cause the destabilization of the atheromatic plaque acting on calcification process as well as inflammation.     

Characterization of coronary atherosclerotic plaques by multidetector computed tomography

Multidetector computed tomography (MDCT) provides 3-dimensional noninvasive visualization of the coronary arterial tree. We compared MDCT with intravascular ultrasound (IVUS) for assessment of severity of coronary artery stenosis and composition of atherosclerotic plaques in 40 patients (32 men; mean age 52 years, range 33 to 86) with documented coronary artery disease. Cross-sectional images obtained at 10-mm increments were assessed for percent decrease in luminal area. Atherosclerotic plaques were classified by IVUS as soft, fibrous, or calcified. On the matched multidetector computed tomograms, regions of interest of 1 to 3 mm in diameter were placed inside each plaque, and tissue contrast was measured in Hounsfield units. Obstructive coronary artery disease was found in 50 segments by IVUS and 57 segments by MDCT. Sensitivity for detecting obstruction >50% was 86.0% (95% confidence interval 72.6 to 93.7) and specificity was 90.2% (95% confidence interval 83.9 to 94.4). In total, 276 plaques were examined by IVUS and MDCT. There were 188 soft plaques (68.2%), 45 fibrous plaques (16.2%), and 43 calcified plaques (15.5%). Multidetector computed tomographic tissue contrast of soft, fibrous, and calcified plaques were 71.5 +/- 32.1, 116.3 +/- 35.7, and 383.3 +/- 186.1, respectively (p <0.001). Using a cut-off value of 185 HU, 273 of 276 plaques (99%) were correctly classified as calcified or noncalcified plaques. Using a cut-off value of 88 HU, 192 of 233 noncalcified plaques (82%) were correctly classified as fibrous or soft plaques. In conclusion, our data indicate that MDCT can provide important information concerning the composition of atherosclerotic plaques in addition to detecting luminal obstruction.     

高分辨磁共振成像评价颈动脉粥样硬化斑块成分

目的探讨高分辨MRI不同序列检查评价缺血性脑血管病患者颈动脉粥样硬化斑块成分的临床意义。方法选择64例缺血性脑血管病患者,其中短暂性脑缺血发作(TIA)患者18例,脑梗死患者46例。采用头颈联合线圈,行高分辨MRI检查,先后选用三维时间飞跃法、T_1WI、T_2WI和质子加权成像4种不同序列,分析斑块成分。结果 64例患者中,有完整厚纤维帽25例(39.1%)、完整薄纤维帽20例(31.2%)、破损纤维帽19例(29.7%),脂质池和坏死核心53例(82.8%),斑块内钙化44例(68.8%),斑块内出血31例(48.4%),斑块内纤维化33例(51.6%),脑梗死患者与TIA患者各类斑块成分所占比例比较,差异均无统计学意义(P>0.05)。结论高分辨MRI不同序列检查对颈动脉斑块的检测有助于分析斑块的成分特征,确定斑决的稳定性。     

Calcification of elastic fibers in human atherosclerotic plaque

The present study was undertaken to systematically investigate whether calcification of elastic fibers occurs in human atherosclerotic plaques. Fourteen carotid artery segments obtained by endarterectomy were examined by a combination of electron microscopy and cytochemistry. The analysis demonstrated that calcification of elastic fibers occurred in all 14 specimens. Two distinct types of calcification of elastic fibers were identified. In type I calcification, elastin itself was observed to undergo calcification and no visible structural alterations preceded the calcification. In type II of calcification, structural alteration of elastin preceded calcification of elastic fibers and included vacuolization of elastin accompanied by the accumulation of neutral lipids and unesterified cholesterol within altered elastic fibers. In type II calcification, calcified deposits were found to form in an association with unesterified cholesterol. Type II calcification was widespread throughout the plaque matrix while type I calcification occurred only in the deep portions of plaques.     

静脉注射间充质干细胞对兔颈动脉易损斑块的影响

目的探讨静脉注射骨髓间充质干细胞(MSC)对动脉粥样硬化易损斑块(VP)稳定性的影响。方法选择雄性新西兰大白兔30只,随机分为MSC组,VP组,稳定斑块(SP)组,每组10只。分别于细胞移植后3d、1周、2周采集兔血清,ELISA法检测血清高敏C反应蛋白(hs-CRP)、TNF-α、白细胞介素6(IL-6),白细胞介素10(IL-10)水平。10周末处死所有动物,取右侧颈总动脉分别行HE染色观察镜下病变,并测量纤维帽/脂核横截面厚度的比值。结果 SP组粥样硬化斑块形态结构完整,纤维帽较厚,斑块内炎性细胞较少,未见斑块破裂。VP组斑块中心可见大量脂核,表面覆盖较薄纤维帽,肩部可见残存泡沫细胞和大量炎性细胞浸润,部分斑块可见破裂和(或)血栓形成。MSC组形态介于之间。MSC组和SP组纤维帽/脂核比值明显高于VP组(P<0.01)。与VP组比较,MSC组各时间点hs-CRP、TNF-α和IL-6水平明显降低,IL-10水平明显升高(P<0.05,P<0.01);与SP组比较,MSC组和VP组各时间点hs-CRP、TNF-α、IL-6和IL-10水平明显升高(P<0.05,P<0.01)。结论 MSC可降低斑块不稳定性,其机制可能与降低机体炎性因子水平、增加抑炎因子及减轻炎性反应有关。     

2型糖尿病患者颈动脉粥样硬化斑块与骨密度的相关性分析

目的探讨住院2型糖尿病(T2DM)患者不同性别骨量减少(包括骨质疏松与低骨量)相关影响因素及其与颈动脉粥样硬化斑块之间的关系。方法回顾性分析720例T2DM患者的临床资料,将入选对象分为男性组和女性组,每组再分为骨量正常组和骨量减少组,颈动脉有斑块组和颈动脉无斑块组。结果在男性骨量减少组(77例)中,存在粥样斑块68例(88.31%),与骨量正常组(164例)比较,骨量减少组粥样斑块的发生率明显升高(P0.05);斑块形成组骨密度(BMD)明显减低(P0.05)。在女性骨量减少组(255例)中,存在粥样斑块191例(74.90%),与骨量正常组(224例)比较,骨量减少组粥样斑块的发生率明显升高(P0.05);斑块形成组骨密度明显减低(P0.05)。二元Logistic回归分析显示,男性骨量减少的影响因素有年龄(OR=1.059,P=0.002),体质指数(BMI)(OR=0.853,P=0.004),空腹血糖(FBG)(OR=1.138,P=0.044),有无颈动脉斑块(OR=2.514,P=0.035)。女性骨量减少的影响因素有年龄(OR=1.117,P=0.000),绝经年龄(OR=0.946,P=0.031),BMI(OR=0.910,P=0.003)。结论 T2DM患者颈动脉粥样硬化斑块与骨量减少密切相关。女性患者由于增龄等共同危险因素的存在,二者常相伴发生,然而在男性患者中,颈动脉粥样硬化斑块的形成是骨质疏松的危险因素,因此,颈动脉硬化的发展常伴有骨量变化,易发生骨质疏松。     

Ultrasonic tissue characterization of the atherosclerotic carotid artery: histological correlates or carotid integrated backscatter.

Histological abnormalities of the atherosclerotic lesion are closely related to the stability of the plaque. Specifically, the plaque is likely to be unstable if the fibrous cap is thin. However, ultrasonic characterization of the atherosclerotic lesion has not been done from this viewpoint. Thus, in the present study ultrasonic tissue characterization of the carotid atherosclerotic lesion was attempted to assess the stability of the plaque. Integrated ultrasonic backscatter (IBS) in the atherosclerotic lesion was compared with histological findings of the respective tissue in 35 patients with carotid artery stenosis who underwent carotid endarterectomy. Carotid IBS was determined by locating the region-of-interest (ROI) in the center of the atherosclerotic lesion and calibrating by subtracting the IBS in the tunica externa of the vessel from the IBS of the ROI. IBS was also determined at the interface of the plaque, and at this site it was analyzed in relation to the thickness of the fibrous cap. Lipid content, fibrous tissue, thrombus, hemorrhage and calcification were histologically assessed in the respective tissue. Carotid IBS in the lipid lesion (-22.5+/-4.1 dB) was significantly different from that of fibrous, hemorrhagic or calcified lesions (-11.1+/-7.1, -27.5+/-4.1, +2.1+/-6.5 dB, respectively), but there was no significant difference in IBS between the lipid lesion and thrombus (-15.2+/-8.8 dB). IBS was lower in the thin fibrous cap than in the thick lesion (-10.9+/-6.4 vs -2.4+/-6.2 dB, p<0.001). IBS can be used to characterize atherosclerotic lesions in the carotid artery; a low value at the interface suggests a thin fibrous cap, which is frequently associated with unstable plaque.     

Endothelial insulin receptor expression in human atherosclerotic plaques: Linking micro- and macrovascular disease in diabetes?

ObjectiveExogenous insulin use in patients with type 2 diabetes (DM2) has been associated with an increased risk of cardiovascular events. Through which mechanisms insulin may increase atherosclerotic plaque vulnerability is currently unclear. Because insulin has been suggested to promote angiogenesis in diabetic retinopathy and tumors, we hypothesized that insulin enhances intra-plaque angiogenesis.MethodsAn in vitro model of pathological angiogenesis was used to assess the potential of insulin to enhance capillary-like tube formation of human microvascular endothelial cells (hMVEC) into a three dimensional fibrin matrix. In addition, insulin receptor expression within atherosclerotic plaques was visualized in carotid endarterectomy specimens of 20 patients with carotid artery stenosis, using immunohistochemical techniques. Furthermore, microvessel density within atherosclerotic plaques was compared between 68 DM2 patients who received insulin therapy and 97 DM2 patients who had been treated with oral glucose lowering agents only.ResultsInsulin, at a concentration of 10^?8 M, increased capillary-like tube formation of hMVEC 1.7-fold (p < 0.01). Within human atherosclerotic plaques, we observed a specific distribution pattern for the insulin receptor: insulin receptor expression was consistently higher on the endothelial lining of small nascent microvessels compared to more mature microvessels. There was a trend towards an increased microvessel density by 20% in atherosclerotic plaques derived from patients using insulin compared to plaques derived from patients using oral glucose lowering agents only (p = 0.05).ConclusionExogenous insulin use in DM2 patients may contribute to increased plaque vulnerability by stimulating local angiogenesis within atherosclerotic plaques.