RESUMO
Plaque erosion (PE), a distinct etiology of acute coronary syndromes (ACSs), is often overshadowed by plaque ruptures (PRs). Concerning its epidemiology, PE has garnered increasing recognition, with recent studies revealing its prevalence to be approximately 40% among ACS patients, challenging earlier assumptions based on autopsy data. Notably, PE exhibits distinct epidemiological features, preferentially affecting younger demographics, particularly women, and often manifesting as a non-ST-segment elevation myocardial infarction. There are seasonal variations, with PE events being less common in winter, potentially linked to physiological changes and cholesterol solidification, while peaking in summer, warranting further investigation. Moving to molecular mechanisms, PE presents a unique profile characterized by a lesser degree of inflammation compared to PR, with endothelial shear stress emerging as a plausible molecular mechanism. Neutrophil activation, toll-like receptor-2 pathways, and hyaluronidase 2 expression are among the factors implicated in PE pathophysiology, underscoring its multifactorial nature. Advancements in intravascular imaging diagnostics, particularly optical coherence tomography and near-infrared spectroscopy coupled with intravascular ultrasound, offer unprecedented insights into plaque composition and morphology. Artificial intelligence algorithms show promise in enhancing diagnostic accuracy and streamlining image interpretation, augmenting clinician decision-making. Therapeutically, the management of PE evolves, with studies exploring less invasive approaches such as antithrombotic therapy without stenting, particularly in cases identified early through intravascular imaging. Additionally, the potential role of drug-coated balloons in reducing thrombus burden and minimizing future major adverse cardiovascular events warrants further investigation. Looking ahead, the integration of advanced imaging modalities, biomarkers, and artificial intelligence promises to revolutionize the diagnosis and treatment of coronary PE, ushering in a new era of personalized and precise cardiovascular care.
Assuntos
Placa Aterosclerótica , Humanos , Placa Aterosclerótica/patologia , Placa Aterosclerótica/terapia , Tomografia de Coerência Óptica , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/terapia , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/diagnósticoRESUMO
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.
Assuntos
Placa Aterosclerótica , Nanomedicina Teranóstica , Humanos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/terapia , Animais , Nanomedicina Teranóstica/métodos , Nanopartículas/química , Nanopartículas/uso terapêuticoRESUMO
Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.
Assuntos
Aterosclerose , Receptor de Morte Celular Programada 1 , Linfócitos T , Humanos , Aterosclerose/imunologia , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Aterosclerose/terapia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inflamação/patologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/farmacologia , Feminino , Masculino , Estudos Retrospectivos , Receptores de IgG/metabolismo , Placa Aterosclerótica/patologia , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/terapia , Placa Aterosclerótica/tratamento farmacológico , Pessoa de Meia-IdadeRESUMO
ABSTRACT: Atherosclerosis is an insidious and progressive inflammatory disease characterized by the formation of lipid-laden plaques within the intima of arterial walls with potentially devastating consequences. While rupture of vulnerable plaques has been extensively studied, a distinct mechanism known as plaque erosion (PE) has gained recognition and attention in recent years. PE, characterized by the loss of endothelial cell lining in the presence of intact fibrous cap, contributes to a significant and growing proportion of acute coronary events. However, despite a heterogeneous substrate underlying coronary thrombosis, treatment remains identical. This article provides an overview of atherosclerotic PE characteristics and its underlying mechanisms, highlights its clinical implications, and discusses potential therapeutic strategies.
Assuntos
Placa Aterosclerótica , Animais , Humanos , Aterosclerose/patologia , Aterosclerose/metabolismo , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/patologia , Células Endoteliais/patologia , Células Endoteliais/metabolismo , Placa Aterosclerótica/patologia , Placa Aterosclerótica/terapia , Ruptura EspontâneaRESUMO
Drug-coated balloon (DCB) angioplasty is one of the potential approaches to alleviating in-stent restenosis and treating peripheral artery disease. An in-silico model has been developed for sirolimus drug eluted from an inflated balloon in a patient-specific arterial cross-section consisting of fibrous tissue, fibrofatty tissue, dense calcium, necrotic core, and healthy tissue. The convection-diffusion-reaction equation represents the transport of drug, while drug binding, both specific and non-specific, can be modelled as a reaction process. The Brinkman equations describe the interstitial flow in porous tissue. An image processing technique is leveraged for reconstructing the computational domain. The Marker and Cell, and Immersed Boundary Methods are used to solve the set of governing equations. The no-flux interface condition and convection do amplify the tissue content, and the regions of dense calcium and necrotic core limited to or extremely close to the interface pose a clinical threat to DCB therapy. Simulations predict the effects of the positioning and clustering of plaque components in the domain. This study demands extensive intravascular ultrasound-derived virtual histology (VH-IVUS) imaging to understand the plaque morphology and determine the relative positions of different plaque compositions about the lumen-tissue interface, which have a significant impact on arterial pharmacokinetics.
Assuntos
Angioplastia Coronária com Balão , Angioplastia com Balão , Doença da Artéria Coronariana , Placa Aterosclerótica , Humanos , Cálcio , Placa Aterosclerótica/terapia , Artérias/patologia , Necrose , Ultrassonografia de Intervenção/métodos , Doença da Artéria Coronariana/patologiaRESUMO
PURPOSE: The identification of plaque features in the middle cerebral artery (MCA) may help minimize periprocedural complications and select patients suitable for percutaneous transluminal angioplasty and stenting (PTAS). However, relevant research is lacking. METHODS: We retrospectively included patients with symptomatic MCA stenosis who received PTAS. All patients underwent intracranial vessel wall MRI (VWMRI) before surgery. Periprocedural complications (PC) included ischemic and hemorrhagic stroke within 30 days. Stenosis location, MCA shape, plaque eccentricity and distribution, plaque thickness and length, and enhancement ratio were compared between patients with and without PC. RESULTS: Sixty-six patients were included in the study, of which 12.1% (8/66) had PC. Of the eight patients with PC, seven (87.5%) had superior wall plaques. In the non-PC group (n = 58), nine (17%) patients had superior wall plaques. Compared with patients without PC, those with PC had more frequent superior wall plaques (17% vs 87.5%, p < 0.001) and s-shaped MCAs (19% vs 50%, p = 0.071), different stenosis locations (p = 0.012), thicker plaques (1.58 [1.35, 2.00] vs 1.98 [1.73, 2.43], p = 0.038), and less frequent inferior wall plaques (79.2% vs 12.5%, p < 0.001). Multivariate analysis showed that only the presence of superior wall plaques (OR = 41.54 [2.31, 747.54]) was independently associated with PC. CONCLUSION: MCA plaque features were highly correlated with PC in patients with symptomatic MCA stenosis who underwent PTAS.
Assuntos
Arteriosclerose Intracraniana , Placa Aterosclerótica , Acidente Vascular Cerebral , Humanos , Artéria Cerebral Média/diagnóstico por imagem , Constrição Patológica/complicações , Estudos Retrospectivos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/terapia , Placa Aterosclerótica/complicações , Acidente Vascular Cerebral/etiologia , Angioplastia , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/cirurgiaRESUMO
Carotid artery stenting (CAS) represents today an accepted option for the treatment of severe carotid artery stenosis. The evolution of materials, techniques, perioperative medical management and patients' selection, has allowed to progressively reduce CAS complications. However, the main drawback of CAS is still represented by the risk of cerebral embolization, that may occur during several steps of the procedure and also in the early postoperative period. Preoperative carotid plaque morphological characteristics may have a great role in determining the risk of embolization during CAS. This review summarizes the current knowledge on carotid plaque characteristics that may influence the risk of complication during CAS. This information may be important for the optimization of CAS patients' selection and adaptation of the materials and techniques.
Assuntos
Estenose das Carótidas , Embolização Terapêutica , Endarterectomia das Carótidas , Placa Aterosclerótica , Humanos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Stents , Artérias Carótidas , Placa Aterosclerótica/complicações , Placa Aterosclerótica/terapia , Endarterectomia das Carótidas/métodos , Resultado do Tratamento , Fatores de RiscoRESUMO
Atherosclerosis, which is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls, acts as the important cause of most cardiovascular diseases. Except for a lipid-depository and chronic inflammatory, increasing evidences propose that epigenetic modifications are increasingly associated with atherosclerosis and are of interest from both therapeutic and biomarker perspectives. The chronic progressive nature of atherosclerosis has highlighted atherosclerosis heterogeneity and the fact that specific cell types in the complex milieu of the plaque are, by far, not the only initiators and drivers of atherosclerosis. Instead, the ubiquitous effects of cell type are tightly controlled and directed by the epigenetic signature, which, in turn, is affected by many proatherogenic stimuli, including low-density lipoprotein, proinflammatory, and physical forces of blood circulation. In this review, we summarize the role of DNA methylation and histone post-translational modifications in atherosclerosis. The future research directions and potential therapy for the management of atherosclerosis are also discussed. Video Abstract.
Assuntos
Aterosclerose , Placa Aterosclerótica , Humanos , Metilação de DNA , Histonas/metabolismo , Aterosclerose/genética , Aterosclerose/terapia , Aterosclerose/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/terapia , Placa Aterosclerótica/patologia , Epigênese Genética , Processamento de Proteína Pós-Traducional , Inflamação/genéticaRESUMO
Atherosclerosis (AS) is a chronic inflammatory disease of arteries fueled by lipids. It is a major cause of cardiovascular morbidity and mortality. Mesenchymal stem cells have been used for the treatment of atherosclerotic lesions. Adipose-derived stem cells (ADSCs) have been shown to regulate the activation state of macrophages and exhibit anti-inflammatory capabilities. However, the effect of allogeneic ADSCs in the treatment of AS have not been investigated. In this study, the early treatment effect and preliminary mechanism analysis of allogeneic rabbit ADSCs intravenous transplantation were investigated in a high-fat diet rabbit model. The polarization mechanism of rabbit ADSCs on the macrophage was further analyzed in vitro. Compared with the model group, blood lipid levels declined, the plaque area, oxidized low-density lipoprotein (ox-LDL) uptake, scavenger receptor A1 and cluster of differentiation (CD) 36 levels were all significantly reduced, and the accumulation of inflammatory M1 macrophages, apoptosis, interleukin (IL)-6 and tumor necrosis factor (TNF)-α expression were decreased. The endothelial cells (CD31), M2 macrophages, IL-10 and the transforming growth factor (TGF)-ß levels increased. In vitro, ADSCs can promote the M1 macrophage phenotypic switch toward the M2 macrophage through their secreted exosomes, and the main mechanism includes increasing arginase 1 expression and IL-10 secretion, declining inducible nitric oxide synthase (iNOS) expression and TNF-α secretion, and activating the STAT6 pathway. Therefore, allogeneic rabbit ADSC transplantation can transmigrate to the aortic atherosclerotic plaques and show a good effect in lowering blood lipids and alleviating atherosclerotic plaque in the early stage of AS by inhibiting ox-LDL uptake, inflammatory response, and endothelial damage.
Assuntos
Aterosclerose , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Placa Aterosclerótica , Animais , Coelhos , Placa Aterosclerótica/terapia , Placa Aterosclerótica/metabolismo , Interleucina-10/metabolismo , Células Endoteliais/metabolismo , Aterosclerose/metabolismo , Lipoproteínas LDL/metabolismo , Inflamação , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Células-Tronco Mesenquimais/metabolismo , LipídeosRESUMO
BACKGROUND: Acute coronary syndromes are commonly caused by the rupture of vulnerable plaque, which often appear angiographically not severe. Although pharmacologic management is considered standard therapy for stabilizing plaque vulnerability, the potential role of preventive local treatment for vulnerable plaque has not yet been determined. The PREVENT trial was designed to compare preventive percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) with OMT alone in patients with functionally nonsignificant high-risk vulnerable plaques. METHODS: The PREVENT trial is a multinational, multicenter, prospective, open-label, active-treatment-controlled randomized trial. Eligible patients have at least 1 angiographically significant stenosis (diameter stenosis >50% by visual estimation) without functional significance (fractional flow reserve [FFR] >0.80). Target lesions are assessed by intracoronary imaging and must meet at least 2 imaging criteria for vulnerable plaque; (1) minimal lumen area <4.0 mm2; (2) plaque burden >70%; (3) maximal lipid core burden index in a 4 mm segment >315 by near infrared spectroscopy; and (4) thin cap fibroatheroma as determined by virtual histology or optical coherence tomography. Enrolled patients are randomly assigned in a 1:1 ratio to either preventive PCI with either bioabsorbable vascular scaffolds or metallic everolimus-eluting stents plus OMT or OMT alone. The primary endpoint is target-vessel failure, defined as the composite of death from cardiac causes, target-vessel myocardial infarction, ischemic-driven target-vessel revascularization, or hospitalization for unstable or progressive angina, at 2 years after randomization. RESULTS: Enrollment of a total of 1,608 patients has been completed. Follow-up of the last enrolled patient will be completed in September 2023 and primary results are expected to be available in early 2024. CONCLUSIONS: The PREVENT trial is the first large-scale, randomized trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaques containing multiple high-risk features that is appropriately powered for clinical outcomes. PREVENT will provide compelling evidence as to whether preventive PCI of vulnerable plaques plus OMT improves patient outcomes compared with OMT alone. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02316886. KEY POINTS: The PREVENT trial is the first, large-scale randomized clinical trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaque with high-risk features. It will provide compelling evidence to determine whether PCI of focal vulnerable plaques on top of OMT improves patient outcomes.
Assuntos
Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/terapia , Placa Aterosclerótica/etiologia , Angiografia Coronária/métodos , Intervenção Coronária Percutânea/métodos , Constrição Patológica , Resultado do Tratamento , Estudos Prospectivos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/etiologiaRESUMO
A patient in their 70s presented with weakness of the left limb and aphasia. Left vertebral angiography showed acute basilar artery occlusion. After mechanical thrombectomy, basilar artery trunk stenosis was evident and catheter-based near-infrared spectroscopy (NIRS) showed lipid-rich atherosclerotic plaque extending to almost 220° of the vessel circumference in the culprit lesion. Loading doses of dual antiplatelet therapy and aggressive medical treatment were started because additional intervention might have increased risk of plaque protrusion and thrombotic reocclusion. The patient presented with minor stroke caused by restenosis of the basilar artery 4 months later; balloon angioplasty and stenting were performed without thromboembolic complications. The patient was discharged without any new neurologic deficits. NIRS visualizes the distribution of lipids in the culprit lesion and the plaque burden of residual stenosis, identifies mechanisms of in situ thrombosis, and provides suggestions for the timing of additional interventions.
Assuntos
Aterosclerose , Placa Aterosclerótica , Acidente Vascular Cerebral , Trombose , Insuficiência Vertebrobasilar , Humanos , Constrição Patológica/complicações , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Placa Aterosclerótica/terapia , Aterosclerose/complicações , Acidente Vascular Cerebral/etiologia , Trombose/complicações , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/cirurgia , Insuficiência Vertebrobasilar/complicaçõesRESUMO
Intracranial branch atheromatous disease (BAD) is a pathological condition characterized by the occlusion of a relatively large perforating branch (700-800 µm) near the orifice of a parent artery due to atherosclerotic plaque-based thrombus (microatheroma). BAD is refractory to treatment and follows a course of progressive exacerbation, especially motor paralysis. Uniform treatment for common atherothrombotic cerebral infarction or lacunar infarction does not prevent the progressive exacerbation of BAD, and consequently affects functional prognosis. To date, various combinations of treatments have been investigated and proposed to attenuate the worsening symptoms of BAD. However, no therapy with established efficacy is yet available for BAD. Since it is the most difficult condition to treat in the area of cerebral infarction, the establishment of optimal treatment methods for BAD is keenly awaited. This review presents an overview of the acute treatments available for BAD and discusses the prospects for optimal treatment.
Assuntos
Trombose Intracraniana , Placa Aterosclerótica , Placa Aterosclerótica/fisiopatologia , Placa Aterosclerótica/terapia , Humanos , Trombose Intracraniana/fisiopatologia , Trombose Intracraniana/terapia , Infarto Cerebral , Acidente Vascular Cerebral Lacunar , Terapia Antiplaquetária DuplaRESUMO
Cardiovascular disease caused by atherosclerosis remains the main reason of death in the worldwide scale. Although oxidative stress plays a key role in the initiation and progression of atherosclerosis, current antioxidant drugs have limited efficacy. To resolve this problem, we constructed Nox2 siRNA-loaded nanobubbles (PNBs-siNox2) coated with platelet membranes to utilize their antioxidant stress activity and targeting effect for atherosclerosis treatment. After platelet membranes modification, the capacity of PNBs-siNox2 to target collagen, foam cells, or human umbilical vein endothelial cells (HUVECs) was significantly increased. Moreover, our study demonstrated that under ultrasonic irradiation, biomimetic nanobubbles were more effective at targeting atherosclerotic plaques and delivering genes into cells. In the present study, we provided a biomimetic gene loading strategy based on nanoplatform for noninvasive, precise and efficient therapy of atherosclerosis, which further improved the efficiency of gene transfection and effectively slowed the progression of atherosclerotic plaques when combined with ultrasound.
Assuntos
Aterosclerose , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/genética , Placa Aterosclerótica/terapia , Antioxidantes/farmacologia , Biomimética , Aterosclerose/terapia , Aterosclerose/genética , Células Endoteliais da Veia Umbilical HumanaRESUMO
Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play a key role in the formation and rupture of atherosclerotic plaques. Previous studies have confirmed that microRNA-145 (miR-145) is involved in the phenotypic regulation of VSMCs and reduction of atherosclerosis. At present, seeking safe and effective gene delivery remains a key problem restricting the development of gene therapy. In recent years, ultrasound-targeted microbubble destruction (UTMD) has become a safe and effective transfection method that is widely used in the basic research of gene therapy for heart and tumor diseases. Here, we synthesized cationic microbubbles to encapsulate miR-145 and targeted their release into VSMCs in vitro and in vivo using ultrasound. The feasibility of this gene therapy was verified by fluorescence microscopy and an in vivo imaging system. The results showed that treatment with miR-145 delivered via UTMD considerably improved the gene transfection efficiency and promoted the contraction phenotype of VSMCs in vitro. In vivo, this treatment reduced the atherosclerotic plaque area by 48.04% compared with treatment with free miR-145. Therefore, UTMD-mediated miRNA therapy may provide a new targeted therapeutic approach for atherosclerotic plaques.
Assuntos
Aterosclerose , MicroRNAs , Placa Aterosclerótica , Camundongos , Animais , MicroRNAs/genética , MicroRNAs/uso terapêutico , Placa Aterosclerótica/terapia , Placa Aterosclerótica/tratamento farmacológico , Microbolhas , Aterosclerose/terapia , AortaRESUMO
Importance: Recent clinical and imaging studies underscore that major adverse cardiac events (MACE) outcomes are associated not solely with severe coronary obstructions (ischemia hypothesis or stenosis hypothesis), but with the plaque burden along the entire coronary tree. New research clarifies the pathobiologic mechanisms responsible for plaque development/progression/destabilization leading to MACE (plaque hypothesis), but the translation of these insights to clinical management strategies has lagged. This narrative review elaborates the plaque hypothesis and explicates the current understanding of underlying pathobiologic mechanisms, the provocative destabilizing influences, the diagnostic and therapeutic implications, and their actionable clinical management approaches to optimize the management of patients with chronic coronary disease. Observations: Clinical trials of management strategies for patients with chronic coronary artery disease demonstrate that while MACE rate increases progressively with the anatomic extent of coronary disease, revascularization of the ischemia-producing obstruction does not forestall MACE. Most severely obstructive coronary lesions often remain quiescent and seldom destabilize to cause a MACE. Coronary lesions that later provoke acute myocardial infarction often do not narrow the lumen critically. Invasive and noninvasive imaging can identify the plaque anatomic characteristics (plaque burden, plaque topography, lipid content) and local hemodynamic/biomechanical characteristics (endothelial shear stress, plaque structural stress, axial plaque stress) that can indicate the propensity of individual plaques to provoke a MACE. Conclusions and Relevance: The pathobiologic construct concerning the culprit region of a plaque most likely to cause a MACE (plaque hypothesis), which incorporates multiple convergent plaque features, informs the evolution of a new management strategy capable of identifying the high-risk portion of plaque wherever it is located along the course of the coronary artery. Ongoing investigations of high-risk plaque features, coupled with technical advances to enable prognostic characterization in real time and at the point of care, will soon enable evaluation of the entire length of the atheromatous coronary artery and broaden the target(s) of our therapeutic intervention to include all regions of the plaque (both flow limiting and nonflow limiting).
Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Isquemia Miocárdica , Placa Aterosclerótica , Humanos , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/diagnóstico , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/terapia , Isquemia Miocárdica/terapia , Fatores de RiscoRESUMO
OBJECTIVES: To investigate the efficacy of medical treatment and balloon angioplasty for intracranial atherosclerosis using high-resolution MR vessel wall imaging (HR-MRI). METHODS: In this prospective study, patients with symptomatic severe stenosis from January 2018 to August 2021 were treated with medical treatment or balloon angioplasty. The patients underwent HR-MRI at baseline and at 3, 6, and 12 months. Plaque characteristics at follow-up were compared with those at baseline using paired sample T-test or Wilcoxon rank sum test. The difference in the recurrence of ischemic events between two groups was compared. RESULTS: A total of 37 patients (26 males; mean age = 60.5 ± 11.6 years) were evaluated. Of 68 plaques, 42 (61.8%) were treated with medication only. At 12 months of medical treatment, maximum plaque length (p = 0.004), maximum wall thickness (p = 0.036), and plaque enhancement (p = 0.001) were significantly reduced than baseline. At 3 months after balloon angioplasty, luminal stenosis (p = 0.048) was significantly reduced compared to baseline. At 6 months after balloon angioplasty, maximum plaque length (p = 0.011), maximum wall thickness (p = 0.003), and luminal stenosis (p = 0.001) were significantly reduced than baseline. No difference was found in the recurrence of ischemic events between two groups (p = 0.458). CONCLUSION: Intracranial atherosclerotic plaque shrank and tended to be stable at 12 months of medical treatment. Plaque burden was significantly reduced 6 months after balloon angioplasty. This may provide evidence for the application and selection of treatment strategies for intracranial atherosclerotic disease. KEY POINTS: ⢠Plaque burden and plaque enhancement were significantly reduced at 12 months of medical treatment compared to baseline. ⢠Plaque burden was significantly reduced at 6 months after balloon angioplasty compared with baseline. ⢠No significant difference in the recurrence rate of ischemic stroke between patients treated with medication and balloon angioplasty.
Assuntos
Angioplastia com Balão , Arteriosclerose Intracraniana , Placa Aterosclerótica , Acidente Vascular Cerebral , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Constrição Patológica/etiologia , Estudos Prospectivos , Imageamento por Ressonância Magnética , Angioplastia com Balão/métodos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/terapia , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/terapia , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: The integrative implications of quantitative and qualitative plaque characteristics on clinical outcomes and therapeutic guidance have not been fully investigated. AIMS: We aimed to investigate the combined prognostic value of quantitative and qualitative plaque measures and their interactions with treatment modalities and physiological lesion severity. METHODS: Among 697 vessels from 458 patients who underwent fractional flow reserve (FFR)-guided treatment, quantitative high-risk plaque (qn-HRP; plaque burden ≥70% and minimum lumen area <3.3 mm2) and qualitative HRP (ql-HRP; low-attenuation plaque or positive remodelling) were defined on coronary computed tomography angiography (CCTA). The primary endpoint was the vessel-oriented composite outcome (VOCO; a composite of cardiac death, myocardial infarction, or revascularisation). RESULTS: The mean baseline FFR was 0.85±0.12, and 25.8% underwent percutaneous coronary intervention (PCI) during the index procedure. In medically treated lesions, both qn-HRP and ql-HRP were associated with an increased risk of VOCO (p<0.05). Relative to the lesions with qn-HRP(-)/ql-HRP(-),those with qn-HRP(+)/ql-HRP(+) showed a higher risk of VOCO (hazard ratio [HR] 8.36, 95% confidence interval [CI]: 2.86-24.44). The PCI group showed a lower risk for VOCO than the medical treatment group (HR 0.31, 95% CI: 0.11-0.91) in lesions with qn-HRP(+)/ql-HRP(+). This difference was consistent in lesions with an FFR of 0.81-0.90 (HR 0.19, 95 CI: 0.04-0.90), but not in those with an FFR of>0.90. CONCLUSIONS: In non-ischaemic lesions, ql-HRP and qn-HRP showed a synergistic impact on risk assessment and had prognostic interactions with FFR and treatment modalities. Therefore, they need to be integrated into risk stratification and the optimisation of a treatment strategy. CLINICALTRIALS: gov: NCT04037163.
Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea , Placa Aterosclerótica , Humanos , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/patologia , Estenose Coronária/terapia , Vasos Coronários/patologia , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/terapia , Placa Aterosclerótica/patologia , Valor Preditivo dos TestesRESUMO
Atherosclerosis is a multifactorial result of complicated pathophysiology. Changes in the expression of polygenes, coupled with environmental and lifestyle factors, trigger a cascade of adverse events involving a variety of cell types, such as vascular endothelial cells, smooth muscle cells, and macrophages. In this review, we summarize the function and therapeutic targets of atherosclerotic cells. This article reviews the role of endothelial cells, smooth muscle cells, macrophages and foam cells in the development of atherosclerosis and the progress in the treatment of atherosclerosis by targeting these cells. Atherosclerotic plaque involves a variety of cells and biomolecules, and its complex biological environment is a difficult point for the study and treatment of atherosclerosis. For treating atherosclerosis, a large number of studies emerged based on blocking or inhibiting factors affecting the formation and development of plaque. Cardiovascular stent intervention is currently the main method for the treatment of atherosclerosis. In recent decades, numerous studies on cardiovascular, stents mainly involve drug coating or biomolecular modification of stents to enhance anti-thrombosis, anti-restenosis and endothelialization. This paper introduces the research status of cardiovascular stents and new strategies for surface modification. The treatment of atherosclerosis based on the level of molecular biology and cell biology is becoming a research hotspot in the coming decades.
Assuntos
Aterosclerose , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/terapia , Placa Aterosclerótica/etiologia , Células Endoteliais/metabolismo , Aterosclerose/terapia , Aterosclerose/metabolismo , Stents/efeitos adversos , Terapia Baseada em Transplante de Células e TecidosRESUMO
OBJECTIVES: A drug-coated balloon (DCB) has potential applications in the treatment of intracranial atherosclerotic disease (ICAD). We aimed to evaluate changes of vessel wall features of ICAD lesions after DCB treatment by using vessel wall MRI (VWMRI). METHODS: We retrospectively included patients with symptomatic ICAD who underwent DCB angioplasty alone. The incidences of stenosis of the lumen area, vessel wall thickening, hyperintense plaques, and prominent wall enhancement were compared between the baseline and follow-up VWMRI. RESULTS: There were 29 ICAD lesions from 29 patients, of which 22 were stenosis and 7 were occlusion. The median interval between DCB treatment and follow-up VWMRI was 4.1 [3.3, 6.7] months. After DCB treatment, follow-up VWMRI showed a significant decrease in the stenosis degree of the lumen area (83% [71%, 96%] vs 15% [3%, 41%], p < 0.001). Thirty-eight percent (11/29) of the patients observed normal appearance of the target vessel wall on follow-up VWMRI. In the stenosis group, the prevalence of hyperintense plaques decreased from 66.7% (14/21) at baseline to 23.8% (5/21) at follow-up, and prominent wall enhancement decreased from 66.7% (14/21) at baseline to 19.0%(4/21) at follow-up. The incidence of hyperintense plaques (p = 0.028) and vessel wall thickening (p = 0.018) tended to decrease with follow-up time. Although not significant (p = 0.106), a similar trend was observed between the incidence of prominent wall enhancement and follow-up time. CONCLUSION: Vascular healing with plaque modification and stabilization occurred following DCB treatment of ICAD lesions. KEY POINTS: ⢠A drug-coated balloon (DCB) has potential applications in the treatment of intracranial atherosclerotic disease (ICAD). ⢠Vascular healing with plaque modification and stabilization occurred following DCB treatment of ICAD lesions.
Assuntos
Angioplastia com Balão , Aterosclerose , Arteriosclerose Intracraniana , Placa Aterosclerótica , Humanos , Constrição Patológica , Estudos Retrospectivos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/terapia , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/cirurgia , Resultado do TratamentoRESUMO
Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and its management places a huge burden on healthcare systems through hospitalisation and treatment. Atherosclerosis is a chronic inflammatory disease of the arterial wall resulting in the formation of lipid-rich, fibrotic plaques under the subendothelium and is a key contributor to the development of CVD. As such, a detailed understanding of the mechanisms involved in the development of atherosclerosis is urgently required for more effective disease treatment and prevention strategies. Heparanase is the only mammalian enzyme known to cleave heparan sulfate of heparan sulfate proteoglycans, which is a key component of the extracellular matrix and basement membrane. By cleaving heparan sulfate, heparanase contributes to the regulation of numerous physiological and pathological processes such as wound healing, inflammation, tumour angiogenesis, and cell migration. Recent evidence suggests a multifactorial role for heparanase in atherosclerosis by promoting underlying inflammatory processes giving rise to plaque formation, as well as regulating lesion stability. This review provides an up-to-date overview of the role of heparanase in physiological and pathological processes with a focus on the emerging role of the enzyme in atherosclerosis.