The ischemia-enhanced myocardial infarction protection-related lncRNA protects against acute myocardial infarction.
MedComm
Long non-coding RNA RP11-64B16.4 (yocardial nfarction rotection-elated ncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re-expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta-8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL-mediated anti-apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia-enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.
10.1002/mco2.632
Personalized Assessment of the Coronary Atherosclerotic Arteries by Intravascular Ultrasound Imaging: Hunting the Vulnerable Plaque.
Journal of personalized medicine
The term "vulnerable plaque" is commonly used to refer to an atherosclerotic plaque that is prone to rupture and the formation of thrombosis, which can lead to several cardiovascular and cerebrovascular events. Coronary artery atherosclerosis has a wide variety of different phenotypes among patients who may have a substantially variable risk for plaque rupture and cardiovascular events. Mounting evidence has proposed three distinctive histopathological mechanisms: plaque rupture, plaque erosion and calcified nodules. Studies have demonstrated the characteristics of plaques with high vulnerability such as the presence of a thin fibrous cap, a necrotic lipid-rich core, abundant infiltrating macrophages and neovascularization. However, traditional coronary angiographic imaging fails to determine plaque vulnerability features, and its ability to individualize treatment strategies is limited. In recent decades, catheter-based intravascular ultrasound imaging (IVUS) modalities have been developed to identify vulnerable plaques and ultimately vulnerable patients. The aim is to individualize prediction, prevention and treatment of acute coronary events based on the identification of specific features of high-risk atherosclerotic plaques, and to identify the most appropriate interventional procedures for their treatment. In this context, the aim of this review is to discuss how personalized assessment of coronary atherosclerotic arteries can be achieved by intravascular ultrasound imaging focusing on vulnerable plaque detection.
10.3390/jpm9010008
Targeting the Microenvironment of Vulnerable Atherosclerotic Plaques: An Emerging Diagnosis and Therapy Strategy for Atherosclerosis.
Advanced materials (Deerfield Beach, Fla.)
Atherosclerosis is considered one of the primary causes of cardiovascular diseases (CVDs). Unpredictable rupture of the vulnerable atherosclerotic plaques triggers adverse cardiovascular events such as acute myocardial syndrome and even sudden cardiac death. Therefore, assessing the vulnerability of atherosclerotic plaques and early intervention are of significance in reducing CVD mortality. Nanomedicine possesses tremendous advantages in achieving the integration of the diagnosis and therapy of atherosclerotic plaques because of its magnetic, optical, thermal, and catalytic properties. Based on the pathological characteristics of vulnerable plaques, stimuli-responsive nanoplatforms and surface-functionalized nanoagents are designed and have drawn great attention for accomplishing the precise imaging and treatment of vulnerable atherosclerotic plaques due to their superior properties, such as high bioavailability, lesion-targeting specificity, on-demand cargo release, and low off-target damage. Here, the characteristics of vulnerable plaques are generalized, and some targeted strategies for boosting the accuracy of plaque vulnerability evaluation by imaging and the efficacy of plaque stabilization therapy (including antioxidant therapy, macrophage depletion therapy, regulation of lipid metabolism therapy, anti-inflammation therapy, etc.) are systematically summarized. In addition, existing challenges and prospects in this field are discussed, and it is believed to provide new thinking for the diagnosis and treatment of CVDs in the near future.
10.1002/adma.202110660
Significance of Intra-plaque Hemorrhage for the Development of High-Risk Vulnerable Plaque: Current Understanding from Basic to Clinical Points of View.
International journal of molecular sciences
Acute coronary syndromes due to atherosclerotic coronary artery disease are a leading cause of morbidity and mortality worldwide. Intra-plaque hemorrhage (IPH), caused by disruption of intra-plaque leaky microvessels, is one of the major contributors of plaque progression, causing a sudden increase in plaque volume and eventually plaque destabilization. IPH and its healing processes are highly complex biological events that involve interactions between multiple types of cells in the plaque, including erythrocyte, macrophages, vascular endothelial cells and vascular smooth muscle cells. Recent investigations have unveiled detailed molecular mechanisms by which IPH leads the development of high-risk "vulnerable" plaque. Current advances in clinical diagnostic imaging modalities, such as magnetic resonance image and intra-coronary optical coherence tomography, increasingly allow us to identify IPH in vivo. To date, retrospective and prospective clinical trials have revealed the significance of IPH as detected by various imaging modalities as a reliable prognostic indicator of high-risk plaque. In this review article, we discuss recent advances in our understanding for the significance of IPH on the development of high-risk plaque from basic to clinical points of view.
10.3390/ijms241713298
Multimodal Intravascular Imaging of the Vulnerable Coronary Plaque.
Echocardiography (Mount Kisco, N.Y.)
Vulnerable coronary plaques are atherosclerotic lesions which, due to their specific phenotype, are prone to plaque rupture and to cause acute coronary syndromes, with subsequent relevant morbidity and mortality. Strategies to break the chain link between plaque vulnerability and adverse clinical events include optimized pharmacologic prevention and potentially also preemptive percutaneous coronary interventions (previously defined as "plaque sealing" or "plaque passivation"). Various morphologic features of the vulnerable plaques have been described, including aspects regarding the large necrotic lipid content, the thin fibrous cap, the presence and extent of the presence of calcifications with small size and calcification angle, and as well as the large macrophage infiltration within the plaque. The detection of these features of plaque vulnerability is possible with intravascular imaging modalities such as intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT). This review explores the peculiarities of these three imaging modalities for the detection of vulnerable coronary plaque features.
10.1111/echo.70035
Current Advances in the Diagnostic Imaging of Atherosclerosis: Insights into the Pathophysiology of Vulnerable Plaque.
Mushenkova Nataliya V,Summerhill Volha I,Zhang Dongwei,Romanenko Elena B,Grechko Andrey V,Orekhov Alexander N
International journal of molecular sciences
Atherosclerosis is a lipoprotein-driven inflammatory disorder leading to a plaque formation at specific sites of the arterial tree. After decades of slow progression, atherosclerotic plaque rupture and formation of thrombi are the major factors responsible for the development of acute coronary syndromes (ACSs). In this regard, the detection of high-risk (vulnerable) plaques is an ultimate goal in the management of atherosclerosis and cardiovascular diseases (CVDs). Vulnerable plaques have specific morphological features that make their detection possible, hence allowing for identification of high-risk patients and the tailoring of therapy. Plaque ruptures predominantly occur amongst lesions characterized as thin-cap fibroatheromas (TCFA). Plaques without a rupture, such as plaque erosions, are also thrombi-forming lesions on the most frequent pathological intimal thickening or fibroatheromas. Many attempts to comprehensively identify vulnerable plaque constituents with different invasive and non-invasive imaging technologies have been made. In this review, advantages and limitations of invasive and non-invasive imaging modalities currently available for the identification of plaque components and morphologic features associated with plaque vulnerability, as well as their clinical diagnostic and prognostic value, were discussed.
10.3390/ijms21082992
From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I.
Naghavi Morteza,Libby Peter,Falk Erling,Casscells S Ward,Litovsky Silvio,Rumberger John,Badimon Juan Jose,Stefanadis Christodoulos,Moreno Pedro,Pasterkamp Gerard,Fayad Zahi,Stone Peter H,Waxman Sergio,Raggi Paolo,Madjid Mohammad,Zarrabi Alireza,Burke Allen,Yuan Chun,Fitzgerald Peter J,Siscovick David S,de Korte Chris L,Aikawa Masanori,Juhani Airaksinen K E,Assmann Gerd,Becker Christoph R,Chesebro James H,Farb Andrew,Galis Zorina S,Jackson Chris,Jang Ik-Kyung,Koenig Wolfgang,Lodder Robert A,March Keith,Demirovic Jasenka,Navab Mohamad,Priori Silvia G,Rekhter Mark D,Bahr Raymond,Grundy Scott M,Mehran Roxana,Colombo Antonio,Boerwinkle Eric,Ballantyne Christie,Insull William,Schwartz Robert S,Vogel Robert,Serruys Patrick W,Hansson Goran K,Faxon David P,Kaul Sanjay,Drexler Helmut,Greenland Philip,Muller James E,Virmani Renu,Ridker Paul M,Zipes Douglas P,Shah Prediman K,Willerson James T
Circulation
Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.
10.1161/01.CIR.0000087480.94275.97
Vulnerable Plaque Imaging.
Seminars in nuclear medicine
Atherosclerotic plaques progress as a result of inflammation. Both invasive and noninvasive imaging techniques have been developed to identify and characterize plaque as vulnerable (more likely to rupture and cause a clinical event). Imaging techniques to identify vulnerable include identifying vessels with focal subendothelial collections of I) inflammatory cells; II) lipid/ fatty acid; III) local regions of hypoxia; IV) local expression of angiogenesis factors; V) local expression of protease; VI) intravascular foci of thrombus; hemorrhage (most often seen in the aftermath of a clinical event); VII) apoptosis and VIII) microcalcification. This review provides an overview of atherosclerotic plaque progression and tracers which can visualize specific molecules associated with vulnerability.
10.1053/j.semnuclmed.2022.08.009
imaging of vulnerable plaque with intravascular modalities: its advantages and limitations.
Kitahara Satoshi,Kataoka Yu,Sugane Hiroki,Otsuka Fumiyuki,Asaumi Yasuhide,Noguchi Teruo,Yasuda Satoshi
Cardiovascular diagnosis and therapy
imaging of plaque instability has been considered to have a great potential to predict future coronary events and evaluate the stabilization effect of novel anti-atherosclerotic medical therapies. Currently, there are several intravascular imaging modalities which enable to visualize plaque components associated with its vulnerability. These include virtual histology intravascular ultrasound (VH-IVUS), integrated backscatter IVUS (IB-IVUS), optical coherence tomography (OCT), near-infrared spectroscopy and coronary angioscopy. Recent studies have shown that these tools are applicable for risk stratification of cardiovascular events as well as drug efficacy assessment. However, several limitation exists in each modality. The current review paper will outline advantages and limitation of VH-IVUS, IB-IVUS, OCT, NIRS and coronary angioscopy imaging.
10.21037/cdt-20-238
Acute left anterior descending artery occlusion after IVUS leading to urgent percutaneous coronary intervention complicated with coronary perforation: Case report.
JRSM cardiovascular disease
Background:Intravascular ultrasonography (IVUS) has become an important complementary tool in interventional cardiology, both for preprocedural planning and for optimizing the performance of percutaneous coronary intervention (PCI). However, this tool is not free of potential complications, because of that it is essential to be aware of them and their management. Over time, new uses of IVUS have emerged, and it is currently a potential tool for predicting the risk of coronary perforation. Case report:We present the clinical case of a 51-year-old male patient who was admitted in the context of post-infarction angina. During coronary angiography, the patient presented with two acute complications, one of them associated with IVUS and the other associated with severe coronary calcification that predisposed to coronary perforation. Both complications were successfully treated. Conclusion:IVUS, although a very useful imaging tool before and during PCI, is not without risk. The overall rate of complications with certain or possible relation to IVUS is 3.9%. Vascular spasm is the most frequent complication and acute vascular occlusion, with the need for emergency coronary artery by-pass grafting, the least frequent. On the other hand, IVUS can predict the risk of developing other complications, such as coronary perforation, by means of the C-CAT sign. Knowledge of the possible complications during PCI and the rapid procedure of the hemodynamic team allows adequate management of these potentially fatal complications.
10.1177/20480040241248924
IVUS plus multivariate analysis for evaluating the stability of coronary artery plaque in coronary heart disease.
Zhang Pengxiang,Li Huixian,Wang Rui,Zhang Aiai,Li Feixing,Li Fangjiang
American journal of translational research
OBJECTIVE:To investigate the effect of intravascular ultrasound (IVUS) plus multivariate analysis in evaluating the stability of coronary artery plaque in coronary heart disease (CHD). METHODS:A retrospective analysis was conducted on ninety-five patients with CHD admitted to our hospital from February 2020 to February 2021. Patients with CHD were examined by IVUS and assigned to a stable plaque group (n=60) and an unstable plaque group (n=35) according to their characteristics. Multivariate regression analysis was performed to evaluate the risk factors affecting the stability of coronary artery plaque. RESULTS:Of 95 patients, 35 cases with unstable plaque were determined by IVUS, with a detection rate of 36.84%; notable differences were found in HDL-C, hs-CRP, and homocysteine (Hcy) between the two groups (P<0.05). The eccentricity index and reconstruction index of the two groups were statistically different (P<0.05). Moreover, 17 cases were diagnosed by IVUS as mild coronary stenosis, 28 cases as moderate stenosis, and 50 cases as severe stenosis. In addition, compared with the stable plaque group, the unstable plaque group yielded a much higher stenosis rate (P<0.05) and a higher level of plaque thickness and plaque area (P<0.05). Multivariate regression analysis showed eccentricity index, remodeling index, plaque thickness, and plaque area, stenosis rate, HDL-C, Hcy, and hs-CRP were independent risk factors for unstable plaque (P<0.05). CONCLUSION:IVUS plus multivariate analysis can accurately assess plaque stability.
Diagnostic performance of IVUS-FFR analysis based on generative adversarial network and bifurcation fractal law for assessing myocardial ischemia.
Frontiers in cardiovascular medicine
Background:IVUS-based virtual FFR (IVUS-FFR) can provide additional functional assessment information to IVUS imaging for the diagnosis of coronary stenosis. IVUS image segmentation and side branch blood flow can affect the accuracy of virtual FFR. The purpose of this study was to evaluate the diagnostic performance of an IVUS-FFR analysis based on generative adversarial networks and bifurcation fractal law, using invasive FFR as a reference. Method:In this study, a total of 108 vessels were retrospectively collected from 87 patients who underwent IVUS and invasive FFR. IVUS-FFR was performed by analysts who were blinded to invasive FFR. We evaluated the diagnostic performance and computation time of IVUS-FFR, and compared it with that of the FFR-branch (considering side branch blood flow by manually extending the side branch from the bifurcation ostia). We also compared the effects of three bifurcation fractal laws on the accuracy of IVUS-FFR. Result:The diagnostic accuracy, sensitivity, and specificity for IVUS-FFR to identify invasive were 90.7% (95% CI, 83.6-95.5), 89.7% (95% CI, 78.8-96.1), 92.0% (95% CI, 80.8-97.8), respectively. A good correlation and agreement between IVUS-FFR and invasive FFR were observed. And the average computation time of IVUS-FFR was shorter than that of FFR-branch. In addition to this, we also observe that the HK model is the most accurate among the three bifurcation fractal laws. Conclusion:Our proposed IVUS-FFR analysis correlates and agrees well with invasive FFR and shows good diagnostic performance. Compared with FFR-branch, IVUS-FFR has the same level of diagnostic performance with significantly lower computation time.
10.3389/fcvm.2023.1155969