Asymmetric dimethylarginine and long-term adverse cardiovascular events in patients with type 2 diabetes: relation with the glycemic control

Patients with type 2 diabetes are at a high risk for acute cardiovascular events, which usually arise from the rupture of a vulnerable coronary lesion characterized by specific morphological plaque features. Thus, the identification of vulnerable plaques is of utmost clinical importance in patients with type 2 diabetes. However, there is currently no scoring system available to identify vulnerable lesions based on plaque characteristics. Thus, we aimed to characterize the diagnostic value of optical coherence tomography (OCT) - derived lesion characteristics to quantify plaque vulnerability both as individual parameters and when combined to a score in patients with type 2 diabetes. OCT was performed in the coronary culprit lesions of 112 patients with type 2 diabetes. The score, which quantifies plaque vulnerability, was defined as the predicted probability that a lesion is the cause for an acute coronary syndrome (ACS) (vs. stable angina (SAP)) based on its specific plaque morphology. Multivariable logistic regression analysis demonstrated that plaque vulnerability was independently predicted by the minimal fibrous cap thickness overlying a lesion’s lipid core (odds ratio (OR) per 10 μm 0.478, p = 0.002), the medium lipid arc (OR per 90° 13.997, p < 0.001), the presence of macrophages (OR 4.797, p = 0.015) and the lipid plaque length (OR 1.290, p = 0.098). Receiver-operating-characteristics (ROC) analyses demonstrated that these parameters combined to a score demonstrate an excellent diagnostic efficiency to identify culprit lesions of patients with ACS (vs. SAP, AUC 0.90, 95% CI 0.84-0.96). This is the first study to present a score to quantify lesion vulnerability in patients with type 2 diabetes. This score may be a valuable adjunct in decision-making and useful in guiding coronary interventions.     

Imagerie moléculaire de la plaque d’athérome vulnérable. Évaluation préclinique et clinique de traceurs radioactifs

Atherosclerotic cardiovascular diseases (CVD) are the leading cause of mortality worldwide, accounting for greater than 19.10⁶ deaths annually. Despite major advances in the treatment of CVD, a high proportion of CVD victims die suddenly while being apparently healthy, the great majority of these accidents being due to the rupture or erosion of a vulnerable coronary atherosclerotic plaque. Indeed, an acute heart attack is the first symptom of atherosclerosis in as much as 50% of individuals with severe disease. A non-invasive imaging methodology allowing the early detection of vulnerable atherosclerosis in selected individuals prior to the occurrence of any symptom would therefore be of great public health benefit. Nuclear imaging could potentially allow the identification of vulnerable patients by non-invasive scintigraphic imaging following administration of a radiolabeled tracer. The development of radiolabeled probes that specifically bind to and allow the in vivo imaging of vulnerable atherosclerotic plaques is therefore the subject of intense ongoing experimental and clinical research. Radiotracers targeted at the inflammatory process seem particularly relevant and promising. Recently, macrophage targeting allowed the experimental in vivo detection of atherosclerosis using either SPECT or PET imaging. A few tracers have also been evaluated clinically. Targeting of apoptosis and macrophage metabolism both allowed the imaging of vulnerable atherosclerotic plaques in the carotid vessels of patients. However, nuclear imaging of vulnerable plaques at the level of the coronary arteries remains a challenging issue because of the small size of atherosclerotic lesions and of their vicinity with blood and the circulating tracer activity.     

冠状动脉易损斑块影像学最新研究进展

冠心病(CAD)是世界上致死率最高的疾病之一,其中,以急性冠状动脉综合征(ACS)病情最为凶险,而近70%的急性冠脉事件并不是由显著地冠状动脉狭窄引起,而是由冠状动脉易损斑块(vulnerable plaque)破裂造成的急性狭窄,以及其后血栓形成所致,因此冠状动脉易损斑块是导致急性冠状动脉综合征的主要元凶,因此需要早期发现易损斑块并积极进行干预。近两年来,CT、MRI、血管内超声(IVUS)和光学相干断层成像(OCT)广泛应用于易损斑块的评估并取得显著进展,而分子影像学能从分子层面揭示易损斑块形成机制以及更加早期识别斑块进行。本文简要总结近两年影像学方法对易损斑块的最新研究进展及热点。     

The emerging role of thrombus aspiration in contemporary percutaneous coronary intervention practice

Coronary atherosclerosis may lead towards thrombogenesis, usually triggered by rupture or erosion of a vulnerable epicardial coronary artery plaque. Most acute coronary syndromes are caused by ruptured atherosclerotic plaques with superimposed thrombus.     

MRI对糖尿病急性脑梗死患者颈动脉粥样硬化斑块稳定性的评估价值

目的:探讨核磁共振成像(MRI)对急性脑梗死合并糖尿病患者颈动脉粥样硬化斑块稳定性的评估价值。方法:选取2013年5月-2015年5月在我院接受治疗的83例糖尿病合并急性脑梗死患者作为研究组,另选择单纯急性脑梗死患者61例作为对照组。两组患者均采用MRI评估颈动脉血管及斑块稳定性,并分析影响颈动脉斑块稳定性的危险因素。结果:研究组患者颈动脉粥样硬化易损斑块的发生率高于对照组,差异具有统计学意义(P0.05);研究组患者斑块最大厚度明显高于对照组,差异具有统计学意义(P0.05);两组患者血管总面积、血管壁面积、血管腔面积及血管壁标准化指数比较,差异均无统计学意义(P0.05)。性别、糖尿病以及饮酒是影响急性脑梗死患者颈动脉斑块稳定性的独立危险因素(P0.05)。结论:MRI能够有效评估急性脑梗死患者颈动脉粥样硬化斑块的稳定性,有利于临床诊断以及确定治疗方案,值得推广应用。     

The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture

Atherosclerosis is the main pathophysiological process underlying coronary artery disease (CAD). Acute complications of atherosclerosis, such as myocardial infarction, are caused by the rupture of vulnerable atherosclerotic plaques, which are characterized by thin, highly inflamed, and collagen-poor fibrous caps. Several lines of evidence mechanistically link the heme peroxidase myeloperoxidase (MPO), inflammation as well as acute and chronic manifestations of atherosclerosis. MPO and MPO-derived oxidants have been shown to contribute to the formation of foam cells, endothelial dysfunction and apoptosis, the activation of latent matrix metalloproteinases, and the expression of tissue factor that can promote the development of vulnerable plaque. As such, detection, quantification and imaging of MPO mass and activity have become useful in cardiac risk stratification, both for disease assessment and in the identification of patients at risk of plaque rupture. This review summarizes the current knowledge about the role of MPO in CAD with a focus on its possible roles in plaque rupture and recent advances to quantify and image MPO in plasma and atherosclerotic plaques.     

A historical perspective towards a non-invasive treatment for patients with atherosclerosis

The history of atherosclerosis and cardiovascular disease dates back to ancient times. From the teachings of Galen to the response-to-injury hypothesis of Russel Ross, we have now arrived at the concept of the vulnerable plaque. Next to the development of new treatment options for patients with atherosclerosis, also novel diagnostic imaging techniques have been developed to visualise the arterial wall and to characterise plaque composition. In this article the historical context of atherosclerosis and the attempts towards a noninvasive therapy for patients with atherosclerotic diseases are described. (Neth Heart J 2009;17: 140–5.)     

中性粒细胞与淋巴细胞比值和冠心病的关系

炎性作用在心血管疾病中的作用越来越重要,尤其是炎性标记物与冠心病之间的相互作用及关系,近年来被广泛研究,大多研究结果呈现一致性。中性粒细胞与淋巴细胞比值是近些年新兴的炎症标记物,其简易、普及、易获取的特点受到了广泛学者的肯定。NLR与动脉粥样硬化相关,相关研究显示动脉僵硬度、钙化积分与NLR密切相关,另外,高NLR者更易发现易损斑块。NLR可预测急性冠脉综合征的短期及长期心血管事件发生率及死亡率,以及预测稳定性心绞痛预后情况及侧支循环是否丰富。在冠脉造影的应用中,发现NLR不仅与冠脉病变严重程度密切相关,能预测完全闭塞病变的发生,及预测无复流的发生。在已有心血管危险因素的基础上,NLR可作为新成员,为冠心病的发现及其预后的风险评价提供依据。     

IVUS-based computational modeling and planar biaxial artery material properties for human coronary plaque vulnerability assessment

Image-based computational modeling has been introduced for vulnerable atherosclerotic plaques to identify critical mechanical conditions which may be used for better plaque assessment and rupture predictions. In vivo patient-specific coronary plaque models are lagging due to limitations on non-invasive image resolution, flow data, and vessel material properties. A framework is proposed to combine intravascular ultrasound (IVUS) imaging, biaxial mechanical testing and computational modeling with fluid-structure interactions and anisotropic material properties to acquire better and more complete plaque data and make more accurate plaque vulnerability assessment and predictions. Impact of pre-shrink-stretch process, vessel curvature and high blood pressure on stress, strain, flow velocity and flow maximum principal shear stress was investigated.     

动脉粥样硬化易损斑块的分子影像研究进展

动脉粥样硬化是心脑血管疾病最主要的病因,而其中易损斑块的突然破损所诱发的血小板聚集和血栓形成是引起脑卒中和急性心肌梗死的重要发病机制.如何更有效地早期诊断动脉粥样硬化的易损斑块是目前研究的热点.文章主要就近年来分子影像技术用于动脉粥样硬化易损斑块的评价研究进行综述.     

Measurement of the transverse strain tensor in the coronary arterial wall from clinical intravascular ultrasound images

Atherosclerotic plaque rupture is the major cause of acute coronary syndromes. Currently, there is no reliable diagnostic tool to predict plaque rupture. Knowledge of plaque mechanical properties based on local artery wall strain measurements would be useful for characterizing its composition and predicting its vulnerability. Due to cardiac motion, strain estimation in clinical intravascular ultrasound (IVUS) images is extremely challenging. A method is presented to estimate cross-sectional coronary artery wall strain in response to cardiac pulsatile pressure using clinically acquired IVUS images, which are acquired in continuous pullback mode. First, cardiac phase information is retrieved retrospectively from an IVUS image sequence using an image-based gating method, and image sub-sequences at systole and diastole are extracted. Then, images at branch sites are used as landmarks to align the two image sub-sequences. Finally, the paired images at each site are registered to measure the 2D strain tensor of the coronary artery cross-section. This method has been successfully applied to IVUS images of a left anterior descending (LAD) coronary artery acquired clinically during a standard procedure. Such complete strain information should be useful for identifying vulnerable plaque.     

冠心病患者颈动脉粥样硬化与血管内皮功能的临床研究价值

目的:探讨颈动脉粥样硬化与血管内皮功能与冠心病患者的相关性。方法:选取114例冠心病患者(54例单支病变和60例多支病变)为观察组和60例健康体检者为对照组,对两组患者动脉粥样硬化及血管内皮功能进行分析。结果:观察组患者TC、TG、HDL及血糖水平均高于对照组,观察组LDL水平显著低于对照组,两组比较差异有统计学意义(P<0.05);观察组患者颈动脉IMT、斑块积分及斑块数明显高于对照组(P<0.05),观察组FMD显著降低(P<0.05),多支病变组病变程度更严重(P<0.05)。结论:颈动脉粥样硬化与血管内皮功能可作为预测冠心病的重要指标,对预防和治疗冠心病具有重要意义。     

Involvement of heparanase in atherosclerosis and other vessel wall pathologies

Heparanase, the sole mammalian endoglycosidase degrading heparan sulfate, is causally involved in cancer metastasis, angiogenesis, inflammation and kidney dysfunction. Despite the wide occurrence and impact of heparan sulfate proteoglycans in vascular biology, the significance of heparanase in vessel wall disorders is underestimated. Blood vessels are highly active structures whose morphology rapidly adapts to maintain vascular function under altered systemic and local conditions. In some pathologies (restenosis, thrombosis, atherosclerosis) this normally beneficial adaptation may be detrimental to overall function. Enzymatic dependent and independent effects of heparanase on arterial structure mechanics and repair closely regulate arterial compliance and neointimal proliferation following endovascular stenting. Additionally, heparanase promotes thrombosis after vascular injury and contributes to a pro-coagulant state in human carotid atherosclerosis. Importantly, heparanase is closely associated with development and progression of atherosclerotic plaques, including stable to unstable plaque transition. Consequently, heparanase levels are markedly increased in the plasma of patients with acute myocardial infarction. Noteworthy, heparanase activates macrophages, resulting in marked induction of cytokine expression associated with plaque progression towards vulnerability. Together, heparanase emerges as a regulator of vulnerable lesion development and potential target for therapeutic intervention in atherosclerosis and related vessel wall complications.     

Plaque Vulnerability as Assessed by Radiofrequency Intravascular Ultrasound in Patients with Valvular Calcification

BackgroundCardiac valvular calcification is associated with the overall coronary plaque burden and considered an independent cardiovascular risk and prognostic factor. The purpose of this study was to evaluate the relationship between the presence of valvular calcification and plaque morphology and/or vulnerability.MethodsTransthoracic echocardiography was used to assess valvular calcification in 280 patients with coronary artery disease who underwent radiofrequency intravascular ultrasound (Virtual Histology IVUS, VH-IVUS). A propensity score–matched cohort of 192 patients (n = 96 in each group) was analyzed. Thin-capped fibroatheroma (TCFA) was defined as a necrotic core (NC) >10% of the plaque area with a plaque burden >40% and NC in contact with the lumen for ≥3 image slices. A remodeling index (lesion/reference vessel area) >1.05 was considered to be positive.ResultsPatients were divided into two groups: any calcification in at least one valve (152 patients) vs. no detectable valvular calcification (128 patients). Groups were similar in terms of age, risk factors, clinical diagnosis, and angiographic analysis after propensity score-matched analysis. Gray-scale IVUS analysis showed that the vessel size, plaque burden, minimal lumen area, and remodeling index were similar. By VH-IVUS, % NC and % dense calcium (DC) were greater in patients with valvular calcification (p = 0.024, and p = 0.016, respectively). However, only % DC was higher at the maximal NC site by propensity score-matched analysis (p = 0.029). The frequency of VH-TCFA occurrence was higher depending on the complexity (p = 0.0064) and severity (p = 0.013) of valvular calcification.ConclusionsThere is a significant relationship between valvular calcifications and VH-IVUS assessment of TCFAs. Valvular calcification indicates a greater atherosclerosis disease complexity (increased calcification of the coronary plaque) and vulnerable coronary plaques (higher incidence of VH-TCFA).     

Atherosclerotic Plaque Destabilization in Mice: A Comparative Study

Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.     

Human neutrophil elastase: mediator and therapeutic target in atherosclerosis

Human neutrophil elastase (HNE) is present within atherosclerotic plaques where it contributes to matrix degradation and weakening of the vessel wall associated with the complications of aneurysm formation and plaque rupture. It is joined by other extracellular proteases in these actions but the broad range of substrates and potency of HNE coupled with the potential for rapid increases in HNE activity associated with neutrophil degranulation in acute coronary syndromes single this disruptive protease out as therapeutic target in atherosclerotic disease. This review summarises the role of HNE in neutrophil-mediated endothelial injury and the evidence for HNE as a mediator of atherosclerotic plaque development. The therapeutic potential of HNE neutralising antiproteases, alpha-1-antitrypsin and elafin, in atherosclerosis, is discussed.     

In vivo Near Infrared Fluorescence (NIRF) Intravascular Molecular Imaging of Inflammatory Plaque,a Multimodal Approach to Imaging of Atherosclerosis

The vascular response to injury is a well-orchestrated inflammatory response triggered by the accumulation of macrophages within the vessel wall leading to an accumulation of lipid-laden intra-luminal plaque, smooth muscle cell proliferation and progressive narrowing of the vessel lumen. The formation of such vulnerable plaques prone to rupture underlies the majority of cases of acute myocardial infarction. The complex molecular and cellular inflammatory cascade is orchestrated by the recruitment of T lymphocytes and macrophages and their paracrine effects on endothelial and smooth muscle cells.¹Molecular imaging in atherosclerosis has evolved into an important clinical and research tool that allows in vivo visualization of inflammation and other biological processes. Several recent examples demonstrate the ability to detect high-risk plaques in patients, and assess the effects of pharmacotherapeutics in atherosclerosis.⁴ While a number of molecular imaging approaches (in particular MRI and PET) can image biological aspects of large vessels such as the carotid arteries, scant options exist for imaging of coronary arteries.² The advent of high-resolution optical imaging strategies, in particular near-infrared fluorescence (NIRF), coupled with activatable fluorescent probes, have enhanced sensitivity and led to the development of new intravascular strategies to improve biological imaging of human coronary atherosclerosis.Near infrared fluorescence (NIRF) molecular imaging utilizes excitation light with a defined band width (650-900 nm) as a source of photons that, when delivered to an optical contrast agent or fluorescent probe, emits fluorescence in the NIR window that can be detected using an appropriate emission filter and a high sensitivity charge-coupled camera. As opposed to visible light, NIR light penetrates deeply into tissue, is markedly less attenuated by endogenous photon absorbers such as hemoglobin, lipid and water, and enables high target-to-background ratios due to reduced autofluorescence in the NIR window. Imaging within the NIR ''window'' can substantially improve the potential for in vivo imaging.^2,5Inflammatory cysteine proteases have been well studied using activatable NIRF probes¹⁰, and play important roles in atherogenesis. Via degradation of the extracellular matrix, cysteine proteases contribute importantly to the progression and complications of atherosclerosis⁸. In particular, the cysteine protease, cathepsin B, is highly expressed and colocalizes with macrophages in experimental murine, rabbit, and human atheromata.^3,6,7 In addition, cathepsin B activity in plaques can be sensed in vivo utilizing a previously described 1-D intravascular near-infrared fluorescence technology⁶, in conjunction with an injectable nanosensor agent that consists of a poly-lysine polymer backbone derivatized with multiple NIR fluorochromes (VM110/Prosense750, ex/em 750/780nm, VisEn Medical, Woburn, MA) that results in strong intramolecular quenching at baseline.¹⁰ Following targeted enzymatic cleavage by cysteine proteases such as cathepsin B (known to colocalize with plaque macrophages), the fluorochromes separate, resulting in substantial amplification of the NIRF signal. Intravascular detection of NIR fluorescence signal by the utilized novel 2D intravascular NIRF catheter now enables high-resolution, geometrically accurate in vivo detection of cathepsin B activity in inflamed plaque. In vivo molecular imaging of atherosclerosis using catheter-based 2D NIRF imaging, as opposed to a prior 1-D spectroscopic approach,⁶ is a novel and promising tool that utilizes augmented protease activity in macrophage-rich plaque to detect vascular inflammation.^11,12 The following research protocol describes the use of an intravascular 2-dimensional NIRF catheter to image and characterize plaque structure utilizing key aspects of plaque biology. It is a translatable platform that when integrated with existing clinical imaging technologies including angiography and intravascular ultrasound (IVUS), offers a unique and novel integrated multimodal molecular imaging technique that distinguishes inflammatory atheromata, and allows detection of intravascular NIRF signals in human-sized coronary arteries.Download video file.^{(61M, mov)}     

hs-CRP、D-二聚体和Lp-PLA2与冠心病患者冠状动脉粥样硬化易损斑块的相关性

目的:研究超敏C反应蛋白(hs-CRP)、D-二聚体和脂蛋白相关磷脂酶A2(Lp-PLA2)与冠心病患者冠状动脉粥样硬化易损斑块的相关性。方法:选择2014年1月~2016年12月在我院进行冠状动脉造影和血管内超声检查的患者106例,按照检查结果分为易损斑块组、稳定斑块组和对照组。检测和比较三组患者的血清hs-CRP、D-二聚体和Lp-PLA2水平,并采用Pearson相关分析探讨其与纤维帽厚度、斑块偏心指数和血管重构指数的相关性。结果:易损斑块组和稳定斑块组的血清hs-CRP、D-二聚体和Lp-PLA2水平明显高于对照组(P0.05),且易损斑块组的血清hs-CRP、D-二聚体和Lp-PLA2水平明显高于稳定斑块组(P0.05)。hs-CRP与纤维帽厚度呈负相关(r=-0.712,P0.05),与斑块偏心指数和血管重构指数呈正相关(r=0.813,0.756,P0.05);D-二聚体与纤维帽厚度呈负相关(r=-0.654,P0.05),与斑块偏心指数和血管重构指数呈正相关(r=0.912,0.853,P0.05);Lp-PLA2与纤维帽厚度呈负相关(r=-0.796,P0.05),与斑块偏心指数和血管重构指数呈正相关(r=0.836,0.729,P0.05)。结论:hs-CRP、D-二聚体和Lp-PLA2与冠心病患者冠状动脉粥样硬化易损斑块具有较高的相关性,可作为评估冠状动脉粥样斑块不稳定性的参考指标。     

In vivo mapping of vascular inflammation using multimodal imaging

Background

Plaque vulnerability to rupture has emerged as a critical correlate to risk of adverse coronary events but there is as yet no clinical method to assess plaque stability in vivo. In the search to identify biomarkers of vulnerable plaques an association has been found between macrophages and plaque stability—the density and pattern of macrophage localization in lesions is indicative of probability to rupture. In very unstable plaques, macrophages are found in high densities and concentrated in the plaque shoulders. Therefore, the ability to map macrophages in plaques could allow noninvasive assessment of plaque stability. We use a multimodality imaging approach to noninvasively map the distribution of macrophages in vivo. The use of multiple modalities allows us to combine the complementary strengths of each modality to better visualize features of interest. Our combined use of Positron Emission Tomography and Magnetic Resonance Imaging (PET/MRI) allows high sensitivity PET screening to identify putative lesions in a whole body view, and high resolution MRI for detailed mapping of biomarker expression in the lesions.

Methodology/Principal Findings

Macromolecular and nanoparticle contrast agents targeted to macrophages were developed and tested in three different mouse and rat models of atherosclerosis in which inflamed vascular plaques form spontaneously and/or are induced by injury. For multimodal detection, the probes were designed to contain gadolinium (T1 MRI) or iron oxide (T2 MRI), and Cu-64 (PET). PET imaging was utilized to identify regions of macrophage accumulation; these regions were further probed by MRI to visualize macrophage distribution at high resolution. In both PET and MR images the probes enhanced contrast at sites of vascular inflammation, but not in normal vessel walls. MRI was able to identify discrete sites of inflammation that were blurred together at the low resolution of PET. Macrophage content in the lesions was confirmed by histology.

Conclusions/Significance

The multimodal imaging approach allowed high-sensitivity and high-resolution mapping of biomarker distribution and may lead to a clinical method to predict plaque probability to rupture.     

Vasa vasorum in plaque angiogenesis, metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: a malignant transformation

Background

Vascularization is an exciting and complex mechanism involving angiogenesis and arteriogenesis. The metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) are associated with multiple metabolic toxicities, which result in reactive oxygen species (ROS) due to an elevated tension of oxidative-redox stress and an accelerated atherosclerosis termed atheroscleropathy.

Results

This atheroscleropathy is associated with accelerated angiogenesis within the vulnerable, thin-cap fibro-atheroma, prone to rupture resulting in acute coronary syndromes (ACS). The resulting intimopathy with its neovascularization due to angiogenesis of the adventitial vasa vasorum (Vv) is prone to intraplaque hemorrhage (IPH). These IPH are associated with destabilization of the vulnerable plaques resulting in plaque erosion and plaque rupture resulting in ACS. In atheroscleropathy the adventitial Vv invades the plaque in a malignant-like fashion and concurrently is associated with chronic inflammation, as macrophages are being deposited within the shoulder regions of these vulnerable plaques. These angiogenic Vv provide a custom delivery vascular network for multiple detrimental substrates, which further accelerates the growth of these vulnerable plaques and atheroscleropathy. There exists a vascularization paradox in MS and T2DM, in that, angiogenesis within the plaque is induced and arteriogenesis is impaired.

Conclusion

This review will attempt to provide a database of knowledge regarding the vascularization process (angiogenesis and arteriogenesis) and its mechanisms to better understand the increased cardiovascular risk and the increased morbidity and mortality associated with MS and T2DM.