Intravascular Ultrasound vs Angiography-Guided Drug-Coated Balloon Angioplasty: The ULTIMATE â ¢ Trial.

BACKGROUND: Drug-coated balloon (DCB) angioplasty seems a safe and effective option for specific de novo coronary lesions. However, the beneficial effect of intravascular ultrasound (IVUS)-guided DCB angioplasty in de novo lesions remains uncertain. OBJECTIVES: This study aimed to assess the benefits of IVUS guidance over angiography guidance during DCB angioplasty in de novo coronary lesions. METHODS: A total of 260 patients with high bleeding risk who had a de novo coronary lesion (reference vessel diameter 2.0-4.0 mm, and lesion length ≤15 mm) were randomly assigned to either an IVUS-guided or an angioplasty-guided DCB angioplasty group. The primary endpoint was in-segment late lumen loss (LLL) at 7 months after procedure. The secondary endpoint was target vessel failure at 6 months. RESULTS: A total of 2 patients in the angiography-guided group and 7 patients in the IVUS-guided group underwent bailout stent implantation (P = 0.172). The primary endpoint of 7-month LLL was 0.03 ± 0.52 mm with angiography guidance vs -0.10 ± 0.34 mm with IVUS guidance (mean difference 0.14 mm; 95% CI: 0.02-0.26; P = 0.025). IVUS guidance was also associated with a larger 7-month minimal lumen diameter (2.06 ± 0.62 mm vs 1.75 ± 0.63 mm; P < 0.001) and a smaller diameter stenosis (28.15% ± 13.88% vs 35.83% ± 17.69%; P = 0.001) compared with angiography guidance. Five target vessel failures occurred at 6 months, with 4 (3.1%) in the angiography-guided group and 1 (0.8%) in the IVUS-guided group (P = 0.370). CONCLUSIONS: This study demonstrated that IVUS-guided DCB angioplasty is associated with a lower LLL in patients with a de novo coronary lesion compared with angiography guidance. (Intravascular Ultrasound Versus Angiography Guided Drug-Coated Balloon [ULTIMATE-III]; NCT04255043).

Probing the interfacial structure of aqueous surfactants through helium atom evaporation.

Dissolved helium atoms evaporate from liquids in super-Maxwellian speed distributions because their interactions are too weak to enforce full thermal equilibration at the surface as they are "squeezed" out of solution. The excess speeds of these He atoms reflect their final interactions with solvent and solute molecules at the surfaces of water and other liquids. We extend this observation by monitoring He atom evaporation from salty water solutions coated with surfactants. These surface-active molecules span neutral, anionic, and cationic amphiphiles: butanol, 3-methyl-1-butanol, pentanol, pentanoic acid, pentanoate, tetrabutylammonium, benzyltrimethylammonium, hexyltrimethylammonium, and dodecyltrimethylammonium, each characterized by surface tension measurements. The helium energy distributions, recorded in vacuum using a salty water microjet, reveal a sharp distinction between neutral and ionic surfactant films. Helium atoms evaporate through neutral surfactant monolayers in speed distributions that are similar to a pure hydrocarbon, reflecting the common alkyl chains of both. In contrast, He atoms appear to evaporate through ionic surfactant layers in distributions that are closer to pure salty water. We speculate that the ionic surfactants distribute themselves more loosely and deeply through the top layers of the aqueous solution than do neutral surfactants, with gaps between the surfactants that may be filled with salty water. This difference is supported by prior molecular dynamics simulations and ion scattering measurements of surfactant solutions.

Transfemoral transcatheter aortic valve replacement with VitaFlowTM valve for pure native aortic regurgitation in patients with high surgical risk: Rationale and design of a prospective, multicenter, and randomized SEASON-AR trial.

BACKGROUND: Previous studies primarily demonstrated that transfemoral transcatheter aortic valve replacement (TAVR) with self-expanding valve appeared to be a safe and feasible treatment for patients with pure native aortic regurgitation (AR). However, the routine application of transfemoral TAVR for pure AR patients lacks support from randomized trials. TRIAL DESIGN: SEASON-AR trial is a prospective, multicenter, randomized, controlled, parallel-group, open-label trial, involving at least 20 sites in China, aiming to enroll 210 patients with pure native severe AR and high surgical risk. All enrolled patients are randomly assigned in a 1:1 fashion to undergo transfemoral TAVR with VitaFlowTM valve and receive guideline-directed medical therapy (GDMT) or to receive GDMT alone. The primary endpoint is the rate of major adverse cardiac events (MACE) at 12 months after the procedure, defined by the composite of all-cause mortality, disabling stroke, and rehospitalization for heart failure. The major secondary endpoints encompass various measures, including procedure-related complications, device success, 6-minute walk distance, and the occurrence of each individual component of the primary endpoint. After hospital discharge, follow-up was conducted through clinical visits or telephone contact at 1, 6, and 12 months. The follow-up will continue annually until 5 years after the index procedure to assess the long-term outcomes. CONCLUSION: SEASON-AR trial is the first study designed to investigate the clinical efficacy and safety of transfemoral TAVR with a self-expanding valve in patients with pure native severe AR with inoperable or high-risk, as compared to medical treatment only.

The plasticity of neuropeptide Y-Y1 receptor system on Tac2 neurons contributes to mechanical hyperknesis during chronic itch.

Rationale: In the physiological states, the act of scratching protects the person from harmful substances, while in certain pathological conditions, the patient suffers from chronic itch, both physically and mentally. Chronic itch sufferers are more sensitive to mechanical stimuli, and mechanical hyperknesis relief is essential for chronic itch treatment. While neuropeptide Y-Y1 receptor (NPY-Y1R) system is known to play a crucial role in modulating mechanical itch in physiological conditions, it is elusive how they are altered during chronic itch. We hypothesize that the negative regulatory effect of Y1Rs on Tac2 neurons, the key neurons that transmit mechanical itch, declines during chronic itch. Methods: We combined transgenic mice, chemogenetic manipulation, immunofluorescence, rabies virus circuit tracing, and electrophysiology to investigate the plasticity of Y1Rs on Tac2 neurons during chronic itch. Results: We found that Tac2 neurons receive direct input from Npy neurons and that inhibition of Npy neurons induces activation of Tac2 neurons. Moreover, the expression of Y1Rs on Tac2 neurons is reduced, and the regulatory effect is also reduced during chronic itch. Conclusion: Our study clarifies the plasticity of Y1Rs on Tac2 neurons during chronic itch and further elucidates the mechanism by which NPY-Y1R system is responsible for modulating mechanical itch. We highlight Y1Rs as a promising therapeutic target for mechanical hyperknesis during chronic itch.

Role of the GRP/GRPR System in Regulating Brain Functions.

Re-examining the relationship between neuropeptide systems and neural circuits will help us to understand more intensively the critical role of neuropeptides in brain function as the neural circuits responsible for specific brain functions are gradually revealed. Gastrin-releasing peptide receptors (GRPRs) are Gαq-coupling neuropeptide receptors and widely distributed in the brain, including hippocampus, amygdala, hypothalamus, nucleus tractus solitarius (NTS), suprachiasmatic nucleus (SCN), paraventricular nucleus of the hypothalamus (PVN), preoptic area of the hypothalamus (POA), preBötzinger complex (preBötC), etc., implying the GRP/GRPR system is involved in modulating multiple brain functions. In this review, we focus on the functionality of GRPR neurons and the regulatory role of the GRP/GRPR system in memory and cognition, fear, depression and anxiety, circadian rhythms, contagious itch, gastric acid secretion, food intake, body temperature, and sighing behavior. It can be found that GRPR is usually centered on a certain brain nucleus or anatomical structure and modulates richer or more specific behaviors by connecting with additional different nuclei. In order to explain the regulatory mechanism of the GRP/GRPR system, more precise intervention methods are needed.

Dissociation dynamics of anionic carbon monoxide in dark states.

A resonant system consisting of an excess electron and a closed-shell atom or molecule, as a temporary negative ion, is usually in doublet-spin states that are analogous to bright states of photoexcitation of the neutral. However, anionic higher-spin states, noted as dark states, are scarcely accessed. Here, we report the dissociation dynamics of CO- in dark quartet resonant states that are formed by electron attachments to electronically excited CO (a3Π). Among the dissociations to O-(2P) + C(3P), O-(2P) + C(1D), and O-(2P) + C(1S), the latter two are spin-forbidden in the quartet-spin resonant states of CO-, while the first process is preferred in 4Σ- and 4Π states. The present finding sheds new light on anionic dark states.

Creation and Reaction of Solvated Electrons at and near the Surface of Water.

Solvated electrons (es-) are among nature's most powerful reactants, with over 2600 reactions investigated in bulk water. These electrons can also be created at and near the surface of water by exposing an aqueous microjet in vacuum to gas-phase sodium atoms, which ionize into es- and Na+ within the top few layers. When a reactive surfactant is added to the jet, the surfactant and es- become coreactants localized in the interfacial region. We report the reaction of es- with the surfactant benzyltrimethylammonium in a 6.7 M LiBr/water microjet at 235 K and pH = 2. The reaction intermediates trimethylamine (TMA) and benzyl radical are identified by mass spectrometry after they evaporate from solution into the gas phase. Their detection demonstrates that TMA can escape before it is protonated and benzyl before it combines with itself or a H atom. Diffusion-reaction calculations indicate that es- reacts on average within 20 Å of the surface and perhaps within the surfactant monolayer itself, while unprotonated TMA evaporates from the top 40 Å. The escape depth exceeds 1300 Å for the more slowly reacting benzyl radical. These proof-of-principle experiments establish an approach for exploring the near-interfacial analogues of aqueous bulk-phase radical chemistry through the evaporation of reaction intermediates into the gas phase.

Self-Adjuvanting Protein Vaccine Conjugated with a Novel Synthetic TLR4 Agonist on Virus-Like Liposome Induces Potent Immunity against SARS-CoV-2.

Exploring potent adjuvants and new vaccine strategies is crucial for the development of protein vaccines. In this work, we synthesized a new TLR4 agonist, structurally simplified lipid A analogue GAP112, as a potent built-in adjuvant to improve the immunogenicity of SARS-CoV-2 spike RBD protein. The new TLR4 agonist GAP112 was site-selectively conjugated on the N-terminus of RBD to construct an adjuvant-protein conjugate vaccine in a liposomal formulation. It is the first time that a TLR4 agonist is site-specifically and quantitatively conjugated to a protein antigen. Compared with an unconjugated mixture of GAP112/RBD, a two-dose immunization of the GAP112-RBD conjugate vaccine strongly activated innate immune cells, elicited a 223-fold increase in RBD-specific antibodies, and markedly enhanced T-cell responses. Antibodies induced by GAP112-RBD also effectively cross-neutralized SARS-CoV-2 variants (Delta/B.1.617.2 and Omicron/B.1.1.529). This conjugate strategy provides an effective method to greatly enhance the immunogenicity of antigen in protein vaccines against SARS-CoV-2 and other diseases.

Vascular Smooth Muscle Cells Phenotypic Switching in Cardiovascular Diseases.

Vascular smooth muscle cells (VSMCs), the major cell type in the arterial vessel wall, have a contractile phenotype that maintains the normal vessel structure and function under physiological conditions. In response to stress or vascular injury, contractile VSMCs can switch to a less differentiated state (synthetic phenotype) to acquire the proliferative, migratory, and synthetic capabilities for tissue reparation. Imbalances in VSMCs phenotypic switching can result in a variety of cardiovascular diseases, including atherosclerosis, in-stent restenosis, aortic aneurysms, and vascular calcification. It is very important to identify the molecular mechanisms regulating VSMCs phenotypic switching to prevent and treat cardiovascular diseases with high morbidity and mortality. However, the key molecular mechanisms and signaling pathways participating in VSMCs phenotypic switching have still not been fully elucidated despite long-term efforts by cardiovascular researchers. In this review, we provide an updated summary of the recent studies and systematic knowledge of VSMCs phenotypic switching in atherosclerosis, in-stent restenosis, aortic aneurysms, and vascular calcification, which may help guide future research and provide novel insights into the prevention and treatment of related diseases.

Exploring Gas-Liquid Reactions with Microjets: Lessons We Are Learning.

Liquid water is all around us: at the beach, in a cloud, from a faucet, inside a spray tower, covering our lungs. It is fascinating to imagine what happens to a reactive gas molecule as it approaches the surface of water in these examples. Some incoming molecules may first be deflected away after colliding with an evaporating water molecule. Those that do strike surface H2O or other surface species may bounce directly off or become momentarily trapped through hydrogen bonding or other attractive forces. The adsorbed gas molecule can then desorb immediately or instead dissolve, passing through the interfacial region and into the bulk, perhaps diffusing back to the surface and evaporating before reacting. Alternatively, it may react with solute or water molecules in the interfacial or bulk regions, and a reaction intermediate or the final product may then desorb into the gas phase. Building a "blow by blow" picture of these pathways is challenging for vacuum-based techniques because of the high vapor pressure of water. In particular, collisions within the thick vapor cloud created by evaporating molecules just above the surface scramble the trajectories and internal states of the gaseous target molecules, hindering construction of gas-liquid reaction mechanisms at the atomic scale that we strive to map out.The introduction of the microjet in 1988 by Faubel, Schlemmer, and Toennies opened up entirely new possibilities. Their inspired solution seems so simple: narrow the end of a glass tube to a diameter smaller than the mean free path of the vapor molecules and then push the liquid through the tube at speeds of a car on a highway. The narrow liquid stream creates a sparse vapor cloud, with water molecules spaced far enough apart that they and the reactant gases interact, at most, weakly. Experimentalists, however, confront a host of challenges: nozzle clogging, unstable jetting, searching for vacuum-compatible solutions, measuring low signal levels, and teasing out artifacts because the slender jet is the smallest surface in the vacuum chamber. In this Account, we describe lessons that we are learning as we explore gases (DCl, (HCOOH)2, N2O5) reacting with water molecules and solute ions in the near-interfacial region of these fast-flowing aqueous microjets.

A non-canonical retina-ipRGCs-SCN-PVT visual pathway for mediating contagious itch behavior.

Contagious itch behavior informs conspecifics of adverse environment and is crucial for the survival of social animals. Gastrin-releasing peptide (GRP) and its receptor (GRPR) in the suprachiasmatic nucleus (SCN) of the hypothalamus mediates contagious itch behavior in mice. Here, we show that intrinsically photosensitive retina ganglion cells (ipRGCs) convey visual itch information, independently of melanopsin, from the retina to GRP neurons via PACAP-PAC1R signaling. Moreover, GRPR neurons relay itch information to the paraventricular nucleus of the thalamus (PVT). Surprisingly, neither the visual cortex nor superior colliculus is involved in contagious itch. In vivo calcium imaging and extracellular recordings reveal contagious itch-specific neural dynamics of GRPR neurons. Thus, we propose that the retina-ipRGC-SCN-PVT pathway constitutes a previously unknown visual pathway that probably evolved for motion vision that encodes salient environmental cues and enables animals to imitate behaviors of conspecifics as an anticipatory mechanism to cope with adverse conditions.

Coronary Bifurcation Lesions.

Percutaneous coronary intervention (PCI) with drug-eluting stent (DES) for the treatment of coronary bifurcation lesions (CBLs) is still technically demanding, mainly because of higher rates of both acute and chronic complication as compared with non-CBLs. Although provisional stenting (PS) is considered as the preferred strategy for most of the CBLs, a systematic two-stent technique (double kissing [DK] crush) should be considered in patients with complex left main (LM)-CBLs or non-LM-CBLs stratified by the DEFINITION criteria. Intracoronary imaging and/or physiologic evaluation should be used to optimize CBLs intervention. PCI with DES for the treatment of CBLs is technically demanding, mainly because of higher rates of both acute and chronic complication as compared with non-CBLs. PS is a default strategy for most of the CBLs. Double kissing (DK) crush is associated with better clinical outcomes compared with PS in patients with complex LM-CBLs or non-LM-CBLs stratified by the DEFINITION criteria. Intracoronary imaging and/or physiologic evaluation are useful tools to guide the treatment of CBLs. The use of drug-coated balloons in CBLs needs further data to support the clinical benefits.

Shared nociceptive dorsal root ganglion neurons participating in acupoint sensitization.

When the body is under pathological stress (injury or disease), the status of associated acupoints changes, including decreased pain threshold. Such changes in acupoint from a "silent" to an "active" state are considered "acupoint sensitization," which has become an important indicator of acupoint selection. However, the mechanism of acupoint sensitization remains unclear. In this study, by retrograde tracing, morphological, chemogenetic, and behavioral methods, we found there are some dorsal root ganglion (DRG) neurons innervating the ST36 acupoint and ipsilateral hind paw (IHP) plantar simultaneously. Inhibition of these shared neurons induced analgesia in the complete Freund's adjuvant (CFA) pain model and obstruction of nociceptive sensation in normal mice, and elevated the mechanical pain threshold (MPT) of ST36 acupoint in the CFA model. Excitation of shared neurons induced pain and declined the MPT of ST36 acupoint. Furthermore, most of the shared DRG neurons express TRPV1, a marker of nociceptive neurons. These results indicate that the shared nociceptive DRG neurons participate in ST36 acupoint sensitization in CFA-induced chronic pain. This raised a neural mechanism of acupoint sensitization at the level of primary sensory transmission.

A New iNKT-Cell Agonist-Adjuvanted SARS-CoV-2 Subunit Vaccine Elicits Robust Neutralizing Antibody Responses.

Adjuvants are essential components of vaccines. Invariant natural killer T (iNKT) cells are a distinct subset of T cells that function to bridge the innate and adaptive immunities and are capable of mediating strong and rapid responses to a range of diseases, including cancer and infectious disease. An increasing amount of evidence suggests that iNKT cells can help fight viral infection. In particular, iNKT-secreting IL-4 is a key mediator of humoral immunity and has a positive correlation with the levels of neutralizing antibodies. As iNKT cell agonists, αGC glycolipid (α-galactosylceramide, or KRN7000) and its analogues as vaccine adjuvants have begun to provide vaccinologists with a new toolset. Herein we found that a new iNKT-cell agonist αGC-CPOEt elicited a strong cytokine response with increased IL-4 production. Remarkably, after three immunizations, SARS-CoV-2 RBD-Fc adjuvanted by αGC-CPOEt evoked robust neutralizing antibody responses that were about 5.5-fold more than those induced by αGC/RBD-Fc and 25-fold greater than those induced by unadjuvanted RBD-Fc. These findings imply that αGC-CPOEt could be investigated further as a new COVID-19 vaccine adjuvant to prevent current and future infectious disease outbreaks.

Water promoted 9-fluorenylmethyloxycarbonyl detachment from amino acids in charged microdroplets.

Aqueous microdroplets exhibit unique properties and can trigger reactions that do not occur in bulk solution. Herein, we have demonstrated that water, in microdroplets, can reduce the energy barrier for the lone H transfer of 9-fluorenylmethyloxycarbonyl and promote its detachment from the amino group. This strategy works on various amino acids and opens opportunities of aqueous microdroplets in triggering organic reactions.

Dissociation Dynamics of Anionic Carbon Dioxide in the Shape Resonant State 2Πu.

Dissociative electron attachments via the lowest shape resonant state 2Πu of CO2-, e- + CO2 → O- + CO, are investigated with our high-resolution anion velocity map imaging apparatus. The production efficiency curve of O- obtained in this work is consistent with those reported previously. The forward-backward asymmetric distribution superimposed on the isotopic background is observed in the time-sliced velocity image of O- yield, implying that the dissociation of CO2-(2Πu) proceeds through a combinational motion of bond stretching and bending. Thereby, the coproduct CO is proposed to be in the rovibrational states. The long-standing arguments about the dissociation dynamics of CO2-(2Πu) are settled.

Characteristics of Zusanli Dorsal Root Ganglion Neurons in Rats and Their Receptor Mechanisms in Response to Adenosine.

Neural systems play important roles in the functions of acupuncture. But the unclear structure and mechanism of acupoints hinder acupuncture standardization and cause the acupuncture effects to be varying or even paradoxical. It has been broadly assumed that the efficacy of acupuncture depends on the biological signals triggered at acupoints and passed up along neural systems. However, as the first station to transmit such signals, the characters of the dorsal root ganglia (DRG) neurons innervating acupoints are still not well elucidated. We adopted Zusanli (ST36) as a representative acupoint and found most DRG neurons innervating ST36 acupoint are middle-size neurons with a single spike firing pattern. This suggests that proprioceptive neurons take on greater possibility than small size nociceptive neurons do to mediate the acupuncture signals. Moreover, we found that adenosine injected into ST36 acupoints could dose- and acupoint-dependently mimic the analgesic effect of acupuncture. However, adenosine could not elicit action potentials in the acutely isolated ST36 DRG neurons, but it inhibited ID currents and increased the areas of overshoots. Further, we found that 4 types of adenosine receptors were all expressed by ST36 DRG neurons, and A1, A2b, and A3 receptors were the principal reactors to adenosine. PERSPECTIVE: This study provides the major characteristics of ST36 DRG neurons, which will help to analyze the neural pathway of acupuncture signals. At the same time, these findings could provide a new possible therapy for pain relief, such as injecting adenosine or corresponding agonists into acupoints.

Lateral Habenula and Its Potential Roles in Pain and Related Behaviors.

The lateral habenula (LHb) is a tiny structure that acts as a hub, relaying signals from the limbic forebrain structures and basal ganglia to the brainstem modulatory area. Facilitated by updated knowledge and more precise manipulation of circuits, the progress in figuring out the neural circuits and functions of the LHb has increased dramatically over the past decade. Importantly, LHb is found to play an integrative role and has profound effects on a variety of behaviors associated with pain, including depression-like and anxiety-like behaviors, antireward or aversion, aggression, defensive behavior, and substance use disorder. Thus, LHb is a potential target for improving pain management and related disorders. In this review, we focused on the functions, related circuits, and neurotransmissions of the LHb in pain processing and related behaviors. A comprehensive understanding of the relationship between the LHb and pain will help to find new pain treatments.

Rationale and design for comparison of non-compliant balloon with drug-coating balloon angioplasty for side branch after provisional stenting for patients with true coronary bifurcation lesions: a prospective, multicentre and randomised DCB-BIF trial.

INTRODUCTION: Provisional stenting using drug-eluting stent is effective for simple coronary bifurcation lesions. Kissing balloon inflation using conventional non-compliant balloon is the primary treatment of side branch (SB) after main vessel (MV) stenting. Drug-coating balloon (DCB) is reported to be associated with less frequent clinical events in in-stent restenosis and small vessel disease. The importance of DCB in bifurcation treatment is understudied. Accordingly, this trial is designed to investigate the superiority of DCB to non-compliant balloon angioplasty for SB after provisional stenting in patients with true coronary bifurcation lesions. METHODS AND ANALYSIS: The DCB-BIF trial is a prospective, multicentre, randomised, superiority trial including 784 patients with true coronary bifurcation lesions. Patients will be randomised in a 1:1 fashion to receive either DCB or non-compliant balloon angioplasty if SB diameter stenosis >70% after MV stenting. The primary endpoint is the composite of major adverse cardiac event at the 1-year follow-up, including cardiac death, myocardial infarction (MI) or clinically driven target lesion revascularisation. The major secondary endpoints include all-cause death, periprocedural MI, spontaneous MI, clinically driven target vessel revascularisation, in-stent restenosis, stroke and individual component of the primary endpoint. The safety endpoint is the risk of stent thrombosis. ETHICS AND DISSEMINATION: The study protocol and informed consent have been reviewed and approved by the Institutional Review Board of all participating centres. The written informed consent for participation in the trial will be obtained from all participants. The results of this study will be published in a peer-reviewed journal and disseminated at conferences. TRIAL REGISTRATION NUMBER: NCT04242134.

Single-Cell RNA Sequencing of the Rat Carotid Arteries Uncovers Potential Cellular Targets of Neointimal Hyperplasia.

Aims: In-stent restenosis (ISR) remains an Achilles heel of drug-eluting stents despite technical advances in devices and procedural techniques. Neointimal hyperplasia (NIH) is the most important pathophysiological process of ISR. The present study mapped normal arteries and stenotic arteries to uncover potential cellular targets of neointimal hyperplasia. Methods and Results: By comparing the left (control) and right (balloon injury) carotid arteries of rats, we mapped 11 clusters in normal arteries and 11 mutual clusters in both the control and experimental groups. Different clusters were categorized into 6 cell types, including vascular smooth muscle cells (VSMCs), fibroblasts, endothelial cells (ECs), macrophages, unknown cells and others. An abnormal cell type expressing both VSMC and fibroblast markers at the same time was termed a transitional cell via pseudotime analysis. Due to the high proportion of VSMCs, we divided them into 6 clusters and analyzed their relationship with VSMC phenotype switching. Moreover, N-myristoyltransferase 1 (NMT1) was verified as a credible VSMC synthetic phenotype marker. Finally, we proposed several novel target genes by disease susceptibility gene analysis, such as Cyp7a1 and Cdk4, which should be validated in future studies. Conclusion: Maps of the heterogeneous cellular landscape in the carotid artery were defined by single-cell RNA sequencing and revealed several cell types with their internal relations in the ISR model. This study highlights the crucial role of VSMC phenotype switching in the progression of neointimal hyperplasia and provides clues regarding the underlying mechanism of NIH.