家兔颈总动脉不稳定斑块模型的建立

目的 建立家兔颈总动脉斑块模型。方法 选取60只雄性纯种的新西兰大白兔,随机分为3组,即球囊损伤+高脂组、高脂喂养组及普通饲料喂养组,每组20只。喂养12周后,分别给予中国斑点蝰蛇毒和组胺药物触发,诱发斑块破裂及血栓形成。结果 球囊损伤+高脂组存活17只白兔中,有38处病变狭窄程度超过50％,并且脂质核心较大、纤维帽的厚度小于65 μm,故判定以上38处病变为易损斑块。高脂喂养组中的19只白兔仅8处可判定为易损斑块;普通饲料喂养组中未见易损斑块。结论 高脂饮食饲养后,进行颈总动脉球囊拉伤制作兔易损斑块模型是切实可行的方法。     

磁共振动态增强扫描成像评价辛伐他汀治疗兔动脉粥样硬化斑块的疗效

目的 探讨磁共振动态增强扫描成像(DCE-MRI)在辛伐他汀治疗动脉粥样硬化斑块疗效评价中的应用价值.方法 选择成年雄性新西兰大白兔30只,随机分为高脂喂养+药物治疗组和高脂喂养组,每组15只.均给予高脂饮食,喂养16w后,高脂喂养+药物治疗组在高脂饲料中加用辛伐他汀喂养至第20周.测定DCE-MRI动脉粥样硬化斑块时间-信号强度曲线参数.使用免疫组化方法标记斑块内巨噬细胞、新生血管内皮细胞.结果 两组高脂喂养后总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)均明显升高,第8、16周两组间比较无显著差异,第20周高脂喂养组血脂水平明显高于高脂喂养+药物治疗组.高脂喂养组动脉粥样硬化斑块内CD31、CD68染色阳性细胞百分比明显高于高脂喂养+药物治疗组.高脂喂养+药物治疗组15只实验兔共检出36处强化动脉粥样硬化斑块,增强扫描均可见强化;高脂喂养组15只实验兔共检出40处强化动脉粥样硬化斑块,增强扫描均可见强化.高脂喂养+药物治疗组首过时相斜率S、斑块最大强化率Smax、斑块峰值信号强度强化后120 s信号强度下降率Soutflow均低于高脂喂养组.结论 DCE-MRI参数S、Soutflow、Smax可以作为一种评价药物治疗动脉粥样硬化斑块疗效的量化指标.     

普罗布考对兔动脉粥样硬化模型C反应蛋白水平的影响及其与斑块稳定性的关系

目的观察兔动脉粥样硬化(AS)模型中C反应蛋白(CRP)的水平与斑块稳定性之间的关系,及普罗布考对CRP水平的影响。方法 20只新西兰大白兔采用随机数字表法分为正常对照组(n=6)、高脂饮食组(n=8)和普罗布考组(n=6)。对照组予普通饲料喂养,高脂饮食组和普罗布考组予高脂饲料喂养。4周后高脂饮食组和普罗布考组行髂动脉内膜球囊损伤术。术后普罗布考组每只大白兔加用普罗布考1g/d口服,10周末取血测血清CRP水平,之后处死动物取损伤处动脉,用HE染色观察动脉病理形态学变化。结果高脂饮食组动脉可见典型的AS斑块形成,普罗布考组无典型斑块形成,内膜增厚较为明显;与高脂饮食组比较,普罗布考组血清CRP水平较低[(8.10±1.02)mg/L比(11.35±2.32)mg/L,P<0.05]。结论 CRP在兔AS模型的表达水平明显增加,与斑块的不稳定性有关,普罗布考有一定的抑制兔AS模型血清CRP表达的作用。     

前列腺素E1对兔动脉粥样硬化易损斑块的影响

目的研究前列腺素E1对兔动脉粥样硬化易损斑块的影响及机制。方法 22只新西兰大白兔高脂饲料(1%胆固醇)喂养2周后,进行腹主动脉球囊损伤术,术后继续高脂喂养,7周后,随机分为模型组、前列腺素E1组和辛伐他汀组,同时改为普通饲料继续喂养4周,13周末,所有兔给予中国斑点蝰蛇毒和组胺进行药物诱发。观察药物干预后血脂、斑块形态、斑块组分及炎症因子的变化。结果前列腺素E1对血脂没有影响;与模型组比较,前列腺素E1组能显著增加斑块的纤维帽厚度(101.72±34.89μm比79.86±16.98μm,P<0.01),减小斑块易损指数(0.94±0.27比3.83±1.45,P<0.01);并且能够显著抑制斑块中巨噬细胞的累积(P<0.01)及其分泌的炎症因子基质金属蛋白酶1和基质金属蛋白酶9的表达(P<0.01),前列腺素E1组与辛伐他汀组比较差异无显著性。结论前列腺素E1能够稳定兔动脉粥样硬化易损斑块,该作用与脂质代谢无关,但与抑制斑块中巨噬细胞的累积及其分泌炎症因子密切相关。     

脑心通胶囊对不稳定斑块兔TLR-2和TLR-4炎性信号转导因子的影响

目的探讨脑心通胶囊稳定易损斑块的机制。方法45只兔给予球囊损伤腹主动脉及高脂饲料喂养,12周末造模兔随机分为自然消退组、脑心通组和辛伐他汀组,每组15只。24周末在腹主动脉斑块处转染携带人野生型p53基因,2周后给予中国斑点蝰蛇毒(CRVV)和组胺触发斑块破裂。于26周末通过免疫组化、WesternBlotting及实时定量RT-PCR分析,检测用药后经p53基因转染处Toll样受体2(TLR-2)、Toll样受体4(TLR-4)和核转录因子κB(NF-κB)的表达。结果转染后动脉粥样硬化斑块处有大量TLR-2、TLR-4和NF-κB表达,尤其集中于内皮细胞和巨噬细胞及炎性细胞浸润处。三者在脑心通组和辛伐他汀组的表达较自然消退组显著降低。结论TLR-2、TLR-4的表达量可预测动脉粥样硬化(AS)斑块的进展,脑心通胶囊可通过降低TLR-2、TLR-4的过度表达而稳定斑块。     

应用液氮损伤建立兔动脉粥样硬化易损斑块模型的研究

目的研究应用液氮温控气体损伤动脉血管内皮并结合高脂饮食的方法建立兔动脉粥样硬化易损斑块模型的方法。方法 24只雄性新西兰兔随机均分成3组,每组8只。实验组在手术后给予液氮温控气体损伤兔左颈总动脉内膜,并继续给予高脂饲料喂养3个月;假手术组仅手术操作,术后继续高脂饲料喂养3个月;空白对照组不行任何操作,给与普通饲料喂养3个月。3组动物在处死前均行鲁塞尔蝰蛇毒+组胺药物触发斑块不稳定,动物在处死后,取左颈总动脉行HE染色后观察血管形态变化,并取血分析炎症细胞因子白细胞介素-2(IL-2)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)在三组中的血清学表达。结果 3个月后,与假手术组和空白对照组相比,实验组有明显易损斑块形成,且炎症因子IL-2、IL-10、TNF-ɑ表达较假手术组和空白对照组均有明显升高,差异均有统计学意义(P0.05)。结论液氮温控气体损伤并结合高脂饮食的方法可成功建立动脉粥样硬化易损斑块模型,且与动脉粥样硬化相关的炎症细胞因子(IL-2、IL-10、TNF-α)表达明显增加。     

冠状动脉粥样硬化斑块破裂的细胞与分子生物学研究进展

近 10年来对冠状动脉粥样硬化斑块生物学和动脉粥样硬化斑块破裂触发的认识迅速加深 ,已明确几种使斑块失稳定的分子和细胞学机制。将来血管病理生理学的研究应以稳定易破裂动脉粥样硬化斑块以及减少动脉粥样硬化斑块破裂后血栓形成为方向。本文介绍了近年来动脉粥样硬化斑块破裂的细胞学及分子生物学研究进展。     

光学相干断层成像检测家兔腹主动脉易损斑块的实验研究

目的评价光学相干断层成像(optical coherence tomography,OCT)在检测易损斑块中的应用价值。方法选取30只雄性纯种的新西兰大白兔,随机分为球囊损伤组(建立家兔腹主动脉易损斑块模型),高脂对照组及正常对照组,每组10只。前2组高脂喂养,喂养12周后,分别给予中国斑点蝰蛇毒和组胺药物触发,诱发斑块破裂及血栓形成后进行OCT,并与病理结果对照检测OCT效果。结果球囊损伤组存活的8只白兔中有10处病变狭窄程度>50%,脂质核心较大、纤维帽厚度>65μm,判定以上10处病变为易损斑块;高脂对照组存活的9只白兔仅3处可判定为易损斑块;正常对照组中未见易损斑块。3组102个OCT图像与病理检测动脉内膜厚度[(20.2±7.6)μmvs(15.2±0.9)μm]、中膜厚度[(453.81±87.2)μmvs(434.2±86.5)μm]、斑块厚度[(392.2±34.5)μmvs(380.2±57.1)μm]比较,差异无统计学意义(P>0.05)。OCT测量球囊损伤组易损斑块和稳定斑块血管外弹力膜面积[(16.01±4.44)μmvs(10.32±2.44)μm]和斑块面积[(8.08±2.37)μmvs(6.80±2.17)μm]比较,差异有统计学意义(P<0.01)。结论 OCT是一种判定易损斑块病变特征的有效手段,可以诊断易损斑块、指导临床制定治疗策略。     

血管内膜表面温度差对识别兔腹主动脉易损斑块的价值

目的 评价血管内膜表面温度差在判定兔腹主动脉易损斑块中的价值.方法 雄性新西兰大白兔20只,给予球囊拉伤腹主动脉加高脂饮食喂养16周,建立兔腹主动脉易损斑块模型.存活的大白兔通过中国斑点蝰蛇毒和组胺触发,诱发斑块破裂以及血栓形成.行兔腹主动脉斑块和周围组织的表面温度差测定.结果 16只实验兔顺利完成模型建立,在这些模型上共发现斑块24处.共进行54次斑块表面温度测量.14只兔有17处光学显微镜下观察切片符合易损斑块的特征,共进行了37次表面温度测量;6只有7处符合纤维性斑块特征,进行了17次表面温度测量;4处为非斑块区,共进行9次测量.易损斑块的表面温度差水平为0.94±0.25℃,而纤维斑块的水平为0.15±0.14℃,非斑块区的水平为0.10±0.08℃.易损斑块的表面温度差较纤维斑块和非斑块区明显增高,有统计学差异(P＜0.01).血管内膜表面温度差大于0.3℃识别兔动脉粥样硬化易损斑块的敏感性和特异性分别为86.5％和85.2％.结论 血管内膜表面温度差的测定有助于识别易损斑块.     

温控气体损伤建立兔动脉粥样硬化易损斑块模型

目的利用持续恒定低温气体损伤血管内皮,结合高脂饮食,建立兔颈动脉粥样硬化易损斑块动物模型。方法新西兰雄性白兔24只,3月龄,随机分为空白对照组、假手术组和温控气体损伤组,每组8只。高脂饮食喂养1周后对温控气体损伤组利用低温气体给予血管内膜损伤处理,假手术组单纯给予有创手术操作,术后两组均继续给予高脂饮食12周;空白对照组给予持续普通饮食。术后13周处死动物,取血管行HE、Masson、弹力纤维、油红O染色,观察血管形态,并做小鼠抗兔巨噬细胞抗体11免疫组织化学染色。结果温控气体损伤组可见薄的纤维帽、大脂质核心,内膜有巨噬细胞及泡沫细胞浸润,部分内皮脱落,斑块出现裂隙,局部小血栓形成,形成典型的易损斑块;假手术组多表现为内膜增生,部分存在小斑块,内皮下见泡沫细胞浸润,符合脂纹期改变,为初级斑块;空白对照组未见斑块形成。结论利用恒定低温气体损伤兔颈动脉内膜结合高脂饮食可建立典型的易损斑块模型,且方便易行。     

Prognostic value of serum LP-PLA2 and hs-CRP in unstable atherosclerotic plaques

To evaluate the prognostic value of LP-PLA2 and hs-CRP to the stability of atherosclerotic plaques. Forty-eight New Zealand White rabbits were randomly divided into control group, stable plaque group, P53 group, and P53 + drug group. Rabbits in the control group were fed a regular diet. Rabbits in stable plaque group, P53 group, and P53 + drug group underwent balloon-induced arterial wall injury and then were fed a diet of 1% cholesterol. Then the rabbits in the P53 group and P53 + drug group underwent Ad5-CMV P53 transfection in the 10th week; The P53 + drug group underwent pharmacologic triggering with Russell's viper venom (RVV) and histamine in 24 h and 48 h before euthanized. Intravascular ultrasound (IVUS) was used before sacrificing of the animal. In the 0 week and 12th week, rabbits underwent fast blood collection from the medium-sized artery of the ears, and the serum LP-PLA2 and hs-CRP level was determined. The animal altherosclerotic (AS) model was successfully gained and the rules of serum LP-PLA2 and hs-CRP level in instable plaque were discovered: serum LP-PLA2 in P53 group and P53 + drug group were significantly different from the control group and the stable group, while hs-CRP failed to differ between the control group and the stable group and succeeded in different degrees of unstable plague. The relationship analysis of serum and IVUS results revealed LP-PLA2 might predict an instability of plaque. Combining serum Lp-PLA2 and hs-CRP has higher specificity in predicting the vulnerability of the plaque.     

兔动脉粥样硬化易损斑块早期预警指标的回归性研究

目的 通过对动脉粥样硬化易损斑块破裂前各项检测指标的回归分析,明确预测易损斑块破裂的最佳指标.方法 40只雄性新西兰纯种兔用球囊损伤腹主动脉+高脂喂养10周,于8周末分为p53基因组(20只)和LacZ基因组(20只),在腹主动脉斑块形成处分别转染携带人野生型p53基因或LacZ基因的重组腺病毒载体,2周后分别给予中国斑点蝰蛇毒(CRVV)和组胺药物触发斑块破裂.应用酶联免疫吸附法(ELISA)检测斑块破裂前血清中的高敏C反应蛋白(hs-CRP)、可溶性细胞间黏附分子-1(sICAM-1)和可溶性血管细胞间黏附分子(sVCAM-1)的变化,免疫比浊法测定血浆中纤维蛋白原的水平,联合应用体表超声心动图、血管内超声(IVUS)显像仪和声学密度定量(AD)技术检测易损斑块破裂前的各项影像学指标及声学密度强度,利用logistic回归分析判断以上各项检测指标与易损斑块破裂的关系.结果两组实验兔在药物触发后有21只兔共34处发生斑块破裂及血栓形成.p53基因组(存活19只)斑块破裂率89.5%(17/19),与LacZ基因组(存活18只)斑块破裂率22.2%(4/18)比较,差异有统计学意义(P＜0.01).药物触发前,斑块破裂组(n=21)hs-CRP水平、体表血管超声测值(腹主动脉内膜中层厚度、峰值速度)、AD值、IVUS测值明显高于斑块未破裂组(n=16),logistic回归分析显示IVUS测值斑块偏心指数(EI)、斑块面积(PA)和血清学sVCAM-1的OR值分别为26.917、19.301和1.339(均P＜0.05),校正的AD值AⅡ-c%的OR值为0.458(P＜0.05).结论 IVUS测值E1、PA、血清学指标sVCAM-1以及AD值是预测斑块易损性的重要指标.

Abstract：

Objective To detect the optimal predictors of vulnerable atherosclerotic plaques. Methods Forty New Zealand white rabbits underwent balloon-induced abdominal aortic wall injury and were fed a high cholesterol and saturated fat diet containing 1% cholesterol for 8 weeks. Rabbits were then randomly divided into two groups: group A ( n = 20, the aortic segments rich in plaques were incubated transluminally with recombinant adenovirus carrying p53 ) and group B [n = 20, incubated transluminally with β galactosidase (LacZ) genes]. Two weeks later, rabbits underwent pharmacological triggering with injection of Chinese Russell's viper venom (CRVV) and histamine. Before pharmacologically triggering,concentrations of hs-CRP, sVCAM-1 and sICAM-1 were measured by means of Enzyme-linkedimmunosorbent assay (ELISA). Fibrinogen was analyzed by nephelometer. Ultrasound imaging, accuracy densitometry (AD) examination and intravascular ultrasound (IVUS) were performed to analyze the in vivo features of vulnerable plaques. Logistic regression was used to detect the predictors for vulnerable plaques. Results The ratio d plaque rupture after pharmacological triggering was significantly higher in group A (89.5% ,17/19) than in group B (22.2%,4/18). Serum hs-CRP level was significantly higher in plaque rupture group than in non-rupture group before pharmacological triggering (P ＜ 0. 05 ). In the meantime, parameters derived from ultrasound imaging [intima-media thickness (IMT) and peak velocity (VP), values of accuracy densitometry], measurements of IVUS [external elastic membrance area (EEMA),plaque area(PA), plaque burden (PB), eccentric index (EI) and remodeling index(RI)]were significantly larger in plaque rupture group than in non-rupture group. Logistic regression showed that EI(OR=26.917),PA(OR=19.301), sVCAM-1(OR=1.339)and AⅡ-c%(OR=0.458)were independent predictors for plaque rupture(all P＜0.05).Conclusion The major predictors of vulnerable plaques were eccentric index (EI) and plaque area(PA), sVCAM-1 and AⅡ-c% in this model.     

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.     

In vivo magnetic resonance imaging of experimental thrombosis in a rabbit model

The process of atherosclerotic plaque disruption has been difficult to monitor because of the lack of an animal model and the limited ability to directly visualize the plaque and overlying thrombus in vivo. Our aim was to validate in vivo magnetic resonance imaging (MRI) of the thrombus formation after pharmacological triggering of plaque disruption in the modified Constantinides animal model of plaque disruption. Atherosclerosis was induced in 9 New Zealand White male rabbits (3 kg) with aortic balloon endothelial injury followed by a high cholesterol (1%) diet for 8 weeks. After baseline (pretrigger) MRI, the rabbits underwent pharmacological triggering with Russell's viper venom and histamine, followed by another MRI 48 hours later. Contiguous cross-sectional T2-weighted fast spin echo images of the abdominal aorta were compared by histopathology. In all animals, aortic wall thickening was present on the pretrigger MRI. On MRIs performed 48 hours after triggering, a histologically confirmed intraluminal thrombus was visualized in 6 (67%) of the 9 animals. MRI data correlated with the histopathology regarding aortic wall thickness (R=0.77, P<0.0005), thrombus size (R=0.82, P<0.0001), thrombus length (R=0.86, P<0.005), and anatomic location (R=0.98, P<0.0001). In vivo, MRI reliably determines the presence, location, and size of the thrombus in this animal model of atherosclerosis and plaque disruption. The combination of in vivo MRI and the modified Constantinides animal model could be an important research tool for our understanding of the pathogenesis of acute coronary syndromes.     

卡托普利、缬沙坦对兔动脉粥样硬化斑块的干预作用

目的观察高胆固醇饮食造成兔大动脉粥样斑块形成过程中卡托普利和缬沙坦对大动脉粥样斑块形成的干预作用。方法30只健康雄性新西兰兔随机分为高脂饮食组(A组),高脂饮食加卡托普利组(B组),高脂饮食加缬沙坦组(C组)和对照组(D组)喂养10周后,行超声检测腹主动脉内膜中膜的厚度。并行病理观察血管内膜以及血管内皮细胞情况。结果A组腹主动脉壁粥样斑块形成,血管内膜增厚;B组和C组血管壁有少量粥样斑块形成,血管内膜增厚均较A组明显减轻(P<0.01)。结论卡托普利和缬沙坦具有抗高胆固醇血症致动脉壁粥样斑块形成的确切效果。     

依折麦布辛伐他汀片对兔腹主动脉粥样硬化斑块逆转作用的实验研究

目的：观察腹主动脉粥样斑块内炎性巨噬细胞和平滑肌细胞的表达情况,以探索依折麦布联合他汀类药物在逆转动脉斑块中的作用及机制。方法选取24只健康雄性新西兰大耳白兔,随机分为对照组（n＝8）和高胆固醇血症组（n＝16）。对照组给予普通饲料,喂养12周。高胆固醇血症组喂饲致动脉粥样硬化饲料（由普通颗粒饲料＋15g/L胆固醇＋100g/L猪油＋150g/L蛋黄粉组成）2周后行腹主动脉内膜球囊拉伤术,术后再随机分为模型亚组和依折麦布辛伐他汀（ES）亚组（给予5/10mg/（kg·d）每组8只,两亚组均继续喂饲致动脉粥样硬化饲料10周。喂养第12周时活杀动物,取腹主动脉进行石蜡切片。检测不同时间点脂质和脂蛋白,应用光学显微镜观察动脉粥样硬化进程,采用免疫组化方法分析巨噬细胞和平滑肌细胞在斑块处的表达。结果 ES亚组的血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）浓度明显低于模型亚组（P＜0.01）。病理检测显示两亚组及ES亚组斑块直径、斑块厚度和动脉内/中膜厚度经单因素方差分析,差异有统计学意义（P＜0.05）。免疫组化检测结果示ES亚组血管壁中巨噬细胞的表达量较模型亚组显著减少（P＜0.05）,而平滑肌细胞的表达量较模型亚组显著增多（P＜0.01）。结论 ES可能通过减少细胞外脂质的沉积,减少内膜和中膜巨噬细胞的数量和胆固醇的含量,增加胶原和平滑肌细胞面积,从而起到逆转斑块的作用。     

Arterial wall cholesterol content is a predictor of development and severity of arterial thrombosis

Background: It is unclear if total cholesterol content contributes to the severity of cardiovascular events by affecting the amount of thrombosis. This study evaluated relationships between cholesterol levels and the amount of thrombosis in an atherosclerotic rabbit model of plaque disruption and thrombosis. Methods: Three groups of NZW rabbits were used: normal rabbits (Group I, n = 4); atherosclerotic rabbits (Group II, n = 4); and atherosclerotic rabbits with pharmacologically triggered thrombosis (Group III, n = 16). Atherosclerosis was induced by feeding a cholesterol enriched diet and balloon deendothelialization. At post-mortem, platelet-rich thrombus and arterial wall cholesterol were quantified and histology performed by light and electron microscopy. Results: Arterial wall cholesterol was strongly correlated to serum cholesterol in all groups (r = 0.94, p < 0.0001). There was a significant correlation between the thrombus surface area with arterial wall cholesterol in Group III (r = 0.71, p < 0.002). Serum cholesterol, arterial wall cholesterol, and thrombus surface area were all significantly correlated but only arterial wall cholesterol was an independent predictor of thrombosis. A threshold specific for this model was noted for serum and arterial cholesterol levels above which thrombosis consistently occurred. Conclusions: Arterial wall cholesterol was strongly correlated to serum cholesterol and thrombosis severity. Serum cholesterol, arterial wall cholesterol and thrombus surface area were all integrally related. Condensed Abstract A model of plaque disruption and thrombosis was used to demonstrate a correlation between serum and arterial wall cholesterol (r = 0.94; p < 0.0001); arterial wall cholesterol and the amount of thrombosis (surface area; r = 0.71, p < 0.002). A threshold of serum and arterial cholesterol was determined at which thrombosis occurred in this model.     

Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism

Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis—often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy.