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Journal of Internal Medicine Nov 2015Atherosclerosis is a systemic condition that eventually evolves into vulnerable plaques and cardiovascular events. Pathology studies reveal that rupture-prone... (Review)
Review
Atherosclerosis is a systemic condition that eventually evolves into vulnerable plaques and cardiovascular events. Pathology studies reveal that rupture-prone atherosclerotic plaques have a distinct morphology, namely a thin, inflamed fibrous cap covering a large lipidic and necrotic core. With the fast development of imaging techniques in the last decades, detecting vulnerable plaques thereby identifying individuals at high risk for cardiovascular events has become of major interest. Yet, in current clinical practice, there is no routine use of any vascular imaging modality to assess plaque characteristics as each unique technique has its pros and cons. This review describes the techniques that may evolve into screening tool for the detection of the vulnerable plaque. Finally, it seems that plaque morphology has been changing in the last decades leading to a higher prevalence of 'stable' atherosclerotic plaques, possibly due to the implementation of primary prevention strategies or other approaches. Therefore, the nomenclature of vulnerable plaque lesions should be very carefully defined in all studies.
Topics: Acute Coronary Syndrome; Biomarkers; Diagnostic Imaging; Humans; Plaque, Atherosclerotic; Predictive Value of Tests; Reproducibility of Results; Rupture, Spontaneous; Stroke
PubMed: 26306911
DOI: 10.1111/joim.12414 -
International Journal of Molecular... Dec 2020Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from...
Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology ( < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the (/) gene, rs35286811, emerged as significantly associated with CVA symptomatology ( = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue ( < 0.0001), and significantly higher in carriers of the rs35286811 risk allele ( < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients ( < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability.
Topics: Carotid Arteries; Humans; Inhibitor of Apoptosis Proteins; Plaque, Atherosclerotic; Polymorphism, Single Nucleotide
PubMed: 33317170
DOI: 10.3390/ijms21249387 -
Molecules (Basel, Switzerland) Aug 2019Atherosclerosis is a chronic long-lasting vascular disease leading to myocardial infarction and stroke. Vulnerable atherosclerotic (AS) plaques are responsible for these... (Review)
Review
Atherosclerosis is a chronic long-lasting vascular disease leading to myocardial infarction and stroke. Vulnerable atherosclerotic (AS) plaques are responsible for these life-threatening clinical endpoints. To more successfully work against atherosclerosis, improvements in early diagnosis and treatment of AS plaque lesions are required. Vulnerable AS plaques are frequently undetectable by conventional imaging because they are non-stenotic. Although blood biomarkers like lipids, C-reactive protein, interleukin-6, troponins, and natriuretic peptides are in pathological ranges, these markers are insufficient in detecting the critical perpetuation of AS anteceding endpoints. Thus, chances to treat the patient in a preventive way are wasted. It is now time to solve this dilemma because clear results indicate a benefit of anti-inflammatory therapy per se without modification of blood lipids (CANTOS Trial, NCT01327846). This fact identifies modulation of immune-mediated inflammation as a new promising point of action for the eradication of fatal atherosclerotic endpoints.
Topics: Adaptive Immunity; Animals; Biomarkers; Disease Susceptibility; Humans; Immune System; Immunity, Innate; Inflammation; Matrix Metalloproteinases; Neovascularization, Pathologic; Plaque, Atherosclerotic
PubMed: 31450823
DOI: 10.3390/molecules24173072 -
Current Opinion in Lipidology Oct 2021Cardiovascular calcification, a common feature of atherosclerotic lesions, has long been known to associate with cardiovascular risk. The roles of lipoproteins in... (Review)
Review
PURPOSE OF REVIEW
Cardiovascular calcification, a common feature of atherosclerotic lesions, has long been known to associate with cardiovascular risk. The roles of lipoproteins in atherosclerosis are also established, and lipid-modifying therapies have shown capacity for plaque regression. However, the association of lipid-modifying therapies with calcification is more complex, and currently no medical therapies have been found to reverse or attenuate calcification in patients. In this review, we summarize recent developments in our understanding of the interplay between lipids and cardiovascular calcification, as well as new imaging modalities for assessing calcified atherosclerotic plaque vulnerability.
RECENT FINDINGS
Recent clinical studies have highlighted the associations of lipoprotein subtypes, such as low-density and high-density lipoprotein particles, as well as lipoprotein (a) [Lp(a)], with coronary calcification and calcific aortic valve disease. Further, evidence continues to emerge for the utility of fused 18F-sodium fluoride positron-emission tomographic and computed tomographic (18F-NaF PET/CT) imaging in characterizing the microarchitecture and vulnerability of atherosclerotic plaque, in both humans and animal models.
SUMMARY
The relationship between lipids and cardiovascular calcification is complex, and new imaging techniques, such as 18F-NaF PET/CT imaging, may allow for better identification of disease-modifying therapies and prediction of calcified plaque progression and stability to help guide clinical management.
Topics: Animals; Humans; Lipids; Plaque, Atherosclerotic; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Sodium Fluoride
PubMed: 34320564
DOI: 10.1097/MOL.0000000000000777 -
Journal of Biomedicine & Biotechnology 2011Atherosclerosis has been studied in animals for almost a century, yet the events leading up to the rupture of an atherosclerotic plaque (the underlying cause of the... (Review)
Review
Atherosclerosis has been studied in animals for almost a century, yet the events leading up to the rupture of an atherosclerotic plaque (the underlying cause of the majority of fatal thrombosis formation) have only been studied in the past decade, due in part to the development of a mouse model of spontaneous plaque rupture. Apolipoprotein E knockout mice, when fed a high-fat diet, consistently develop lesions in the brachiocephalic artery that rupture at a known time point. It is therefore now possible to observe the development of lesions to elucidate the mechanisms behind the rupture of plaques. Critics argue that the model does not replicate the appearance of human atherosclerotic plaque ruptures. The purpose of this review is to highlight the reasons why we should be looking to the apolipoprotein E knockout mouse to further our understanding of plaque rupture.
Topics: Animals; Apolipoproteins E; Atherosclerosis; Brachiocephalic Trunk; Dietary Fats; Disease Models, Animal; Humans; Mice; Mice, Knockout; Plaque, Atherosclerotic; Rupture, Spontaneous
PubMed: 21076539
DOI: 10.1155/2011/379069 -
Revista Espanola de Medicina Nuclear E... 2013This review article is focused on the role of FDG-PET/CT in visualizing atherosclerosis and on the relevance of inflammatory cells such as macrophages and T-lymphocytes... (Review)
Review
This review article is focused on the role of FDG-PET/CT in visualizing atherosclerosis and on the relevance of inflammatory cells such as macrophages and T-lymphocytes in the formation of the atherosclerotic plaque. The vulnerability of the inflammatory plaque and the risk derived from the provocation of cardio- and cerebrovascular incidents independently from the presence of stenotic vessels are discussed as well as the evolution toward calcified plaque. The important role of FDG-PET/CT in early diagnosis of inflammatory plaque is discussed in both animal studies and in clinical setting. The possibility of curing inflammatory plaques, type of drugs, and the possibility of monitoring the anti-inflammatory treatment by FDG-PET/CT are also discussed.
Topics: Disease Progression; Fluorodeoxyglucose F18; Humans; Inflammation; Multimodal Imaging; Plaque, Atherosclerotic; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed
PubMed: 23726249
DOI: 10.1016/j.remn.2013.04.001 -
Circulation Journal : Official Journal... 2013It is now generally recognized that acute coronary syndromes most commonly result from disruption of thin-cap fibroatheroma (TCFA), which is characterized by a large... (Review)
Review
It is now generally recognized that acute coronary syndromes most commonly result from disruption of thin-cap fibroatheroma (TCFA), which is characterized by a large necrotic core with an overlying thin-fibrous cap measuring <65 μm. Recent advances in intracoronary imaging modalities have significantly improved the ability to detect TCFA in vivo. Intravascular ultrasound (IVUS) is perhaps the most promising modality that has been used more than 15 years to evaluate atherosclerotic plaque. IVUS has revealed a lot of the clinical evidence regarding vulnerable plaque detection in live humans. Recently, by analyzing the IVUS acoustic signal before demodulation and scan conversion, IVUS radiofrequency analysis can be used to differentiate adjacent smaller areas of atherosclerotic plaque with heterogeneous composition. Coronary angioscopy allows direct visualization of the coronary artery wall and provides detailed information of the luminal surface of plaque, such as color, thrombus or disruption. Optical coherence tomography imaging, recently been introduced for in vivo human imaging, offers a higher resolution than any other available imaging modality, and can visualize a thin fibrous cap measuring <65 μm. In this review, we will discuss the features and limitations of each imaging modalities for detecting TCFA.
Topics: Angioscopy; Coronary Artery Disease; Coronary Vessels; Humans; Necrosis; Plaque, Atherosclerotic; Reproducibility of Results; Tomography, Optical Coherence; Ultrasonography, Interventional
PubMed: 23370454
DOI: 10.1253/circj.cj-12-1599 -
Advanced Healthcare Materials Jun 2024Atherosclerotic plaque formation is considered the primary pathological mechanism underlying atherosclerotic cardiovascular diseases, leading to severe cardiovascular... (Review)
Review
Atherosclerotic plaque formation is considered the primary pathological mechanism underlying atherosclerotic cardiovascular diseases, leading to severe cardiovascular events such as stroke, acute coronary syndromes, and even sudden cardiac death. Early detection and timely intervention of plaques are challenging due to the lack of typical symptoms in the initial stages. Therefore, precise early detection and intervention play a crucial role in risk stratification of atherosclerotic plaques and achieving favorable post-interventional outcomes. The continuously advancing nanoplatforms have demonstrated numerous advantages including high signal-to-noise ratio, enhanced bioavailability, and specific targeting capabilities for imaging agents and therapeutic drugs, enabling effective visualization and management of atherosclerotic plaques. Motivated by these superior properties, various noninvasive imaging modalities for early recognition of plaques in the preliminary stage of atherosclerosis are comprehensively summarized. Additionally, several therapeutic strategies are proposed to enhance the efficacy of treating atherosclerotic plaques. Finally, existing challenges and promising prospects for accelerating clinical translation of nanoplatform-based molecular imaging and therapy for atherosclerotic plaques are discussed. In conclusion, this review provides an insightful perspective on the diagnosis and therapy of atherosclerotic plaques.
Topics: Humans; Plaque, Atherosclerotic; Animals; Theranostic Nanomedicine; Nanoparticles
PubMed: 38564883
DOI: 10.1002/adhm.202303612 -
Theranostics 2021Inflammation is a pivotal driver of atherosclerotic plaque progression and rupture and is a target for identifying vulnerable plaques. However, challenges arise with the...
Inflammation is a pivotal driver of atherosclerotic plaque progression and rupture and is a target for identifying vulnerable plaques. However, challenges arise with the current imaging modalities for differentiating vulnerable atherosclerotic plaques from stable plaques due to their low specificity and sensitivity. Herein, we aimed to develop a novel multimodal imaging platform that specifically targets and identifies high-risk plaques by detecting active myeloperoxidase (MPO), a potential inflammatory marker of vulnerable atherosclerotic plaque. A novel multimodal imaging agent, 5-HT-FeO-Cy7 nanoparticles (5HFeC NPs), used for active MPO targeting, was designed by conjugating superparamagnetic iron oxide nanoparticles (SPIONs) with 5-hydroxytryptamine and cyanine 7 N-hydroxysuccinimide ester. The specificity and sensitivity of 5HFeC NPs were evaluated using magnetic particle imaging (MPI), fluorescence imaging (FLI), and computed tomographic angiography (CTA) in an ApoE atherosclerosis mouse model. Treatment with 4-ABAH, an MPO inhibitor, was used to assess the monitoring ability of 5HFeC NPs. 5HFeC NPs can sensitively differentiate and accurately localize vulnerable atherosclerotic plaques in ApoE mice MPI/FLI/CTA. High MPI and FLI signals were observed in atherosclerotic plaques within the abdominal aorta, which were histologically confirmed by multiple high-risk features of macrophage infiltration, neovascularization, and microcalcification. Inhibition of active MPO reduced accumulation of 5HFeC NPs in the abdominal aorta. Accumulation of 5HFeC NPs in plaques enabled quantitative evaluation of the severity of inflammation and monitoring of MPO activity. This multimodal MPI approach revealed that active MPO-targeted nanoparticles might serve as a method for detecting vulnerable atherosclerotic plaques and monitoring MPO activity.
Topics: Animals; Disease Models, Animal; Magnetic Resonance Imaging; Magnetite Nanoparticles; Male; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE; Optical Imaging; Peroxidase; Plaque, Atherosclerotic
PubMed: 33391489
DOI: 10.7150/thno.49812 -
Journal of Biomedical Optics Dec 2013During the pathogenesis of coronary atherosclerosis, from lesion initiation to rupture, arterial mechanical properties are altered by a number of cellular, molecular,... (Review)
Review
During the pathogenesis of coronary atherosclerosis, from lesion initiation to rupture, arterial mechanical properties are altered by a number of cellular, molecular, and hemodynamic processes. There is growing recognition that mechanical factors may actively drive vascular cell signaling and regulate atherosclerosis disease progression. In advanced plaques, the mechanical properties of the atheroma influence stress distributions in the fibrous cap and mediate plaque rupture resulting in acute coronary events. This review paper explores current optical technologies that provide information on the mechanical properties of arterial tissue to advance our understanding of the mechanical factors involved in atherosclerosis development leading to plaque rupture. The optical approaches discussed include optical microrheology and traction force microscopy that probe the mechanical behavior of single cell and extracellular matrix components, and intravascular imaging modalities including laser speckle rheology, optical coherence elastography, and polarization-sensitive optical coherence tomography to measure the mechanical properties of advanced coronary lesions. Given the wealth of information that these techniques can provide, optical imaging modalities are poised to play an increasingly significant role in elucidating the mechanical aspects of coronary atherosclerosis in the future.
Topics: Biomechanical Phenomena; Elasticity Imaging Techniques; Humans; Plaque, Atherosclerotic; Rheology; Rupture, Spontaneous; Tomography, Optical Coherence
PubMed: 24296995
DOI: 10.1117/1.JBO.18.12.121507