Paricalcitol Has a Potent Anti-Inflammatory Effect in Rat Endothelial Denudation-Induced Intimal Hyperplasia.

Neointimal hyperplasia is the main cause of vascular graft failure in the medium term. Vitamin D receptor activation modulates the biology of vascular smooth muscle cells and has been reported to protect from neointimal hyperplasia following endothelial injury. However, the molecular mechanisms are poorly understood. We have now explored the impact of the selective vitamin D receptor activator, paricalcitol, on neointimal hyperplasia, following guidewire-induced endothelial cell injury in rats, and we have assessed the impact of paricalcitol or vehicle on the expression of key cell stress factors. Guidewire-induced endothelial cell injury caused neointimal hyperplasia and luminal stenosis and upregulated the expression of the growth factor growth/differentiation factor-15 (GDF-15), the cytokine receptor CD74, NFκB-inducing kinase (NIK, an upstream regulator of the proinflammatory transcription factor NFκB) and the chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2). Immunohistochemistry confirmed the increased expression of the cellular proteins CD74 and NIK. Paricalcitol (administered in doses of 750 ng/kg of body weight, every other day) had a non-significant impact on neointimal hyperplasia and luminal stenosis. However, it significantly decreased GDF-15, CD74, NIK and MCP-1/CCL2 mRNA expression, which in paricalcitol-injured arteries remained within the levels found in control vehicle sham arteries. In conclusion, paricalcitol had a dramatic effect, suppressing the stress response to guidewire-induced endothelial cell injury, despite a limited impact on neointimal hyperplasia and luminal stenosis. This observation identifies novel molecular targets of paricalcitol in the vascular system, whose differential expression cannot be justified as a consequence of improved tissue injury.

Improved therapeutic effects on vascular intimal hyperplasia by mesenchymal stem cells expressing MIR155HG that function as a ceRNA for microRNA-205.

Coronary artery bypass grafting (CABG) is an effective treatment for coronary heart disease, with vascular transplantation as the key procedure. Intimal hyperplasia (IH) gradually leads to vascular stenosis, seriously affecting the curative effect of CABG. Mesenchymal stem cells (MSCs) were used to alleviate IH, but the effect was not satisfactory. This work aimed to investigate whether lncRNA MIR155HG could improve the efficacy of MSCs in the treatment of IH and to elucidate the role of the competing endogenous RNA (ceRNA). The effect of MIR155HG on MSCs function was investigated, while the proteins involved were assessed. IH was detected by HE and Van Gieson staining. miRNAs as the target of lncRNA were selected by bioinformatics analysis. qRT-PCR and dual-luciferase reporter assay were performed to verify the binding sites of lncRNA-miRNA. The apoptosis, Elisa and tube formation assay revealed the effect of ceRNA on the endothelial protection of MIR155HG-MSCs. We observed that MIR155HG improved the effect of MSCs on IH by promoting viability and migration. MIR155HG worked as a sponge for miR-205. MIR155HG/miR-205 significantly improved the function of MSCs, avoiding apoptosis and inducing angiogenesis. The improved therapeutic effects of MSCs on IH might be due to the ceRNA role of MIR155HG/miR-205.

Thrombus or tumor? A case report of a rare sarcoma entity: intimal sarcoma of the pulmonary arteries.

BACKGROUND: Tumor embolism is a very rare primary manifestation of cancers and the diagnosis is challenging, especially if located in the pulmonary arteries, where it can mimic nonmalignant pulmonary embolism. Intimal sarcoma is one of the least commonly reported primary tumors of vessels with only a few cases reported worldwide. A typical location of this malignancy is the pulmonary artery. Herein, we present a case report of an intimal sarcoma with primary manifestation in the pulmonary arteries. A 53-year-old male initially presented with dyspnea. On imaging, a pulmonary artery embolism was detected and was followed by thrombectomy of the right ventricular outflow tract, main pulmonary artery trunk, and right pulmonary artery after ineffective lysis therapy. Complementary imaging of the chest and abdomen including a PET-CT scan demonstrated no evidence of a primary tumor. Subsequent pathology assessment suggested an intimal sarcoma further confirmed by DNA methylation based molecular analysis. We initiated adjuvant chemotherapy with doxorubicin. Four months after the completion of adjuvant therapy a follow-up scan revealed a local recurrence without distant metastases. DISCUSSION: Primary pulmonary artery intimal sarcoma (PAS) is an exceedingly rare entity and pathological diagnosis remains challenging. Therefore, the detection of entity-specific molecular alterations is a supporting argument in the diagnostic spectrum. Complete surgical resection is the prognostically most important treatment for intimal cardiac sarcomas. Despite adjuvant chemotherapy, the prognosis of cardiac sarcomas remains very poor. This case of a PAS highlights the difficulty in establishing a diagnosis and the aggressive natural course of the disease. CONCLUSION: In case of atypical presentation of a pulmonary embolism, a tumor originating from the great vessels should be considered. Molecular pathology techniques support in establishing a reliable diagnosis.

Intimomedial tears of the aorta heal by smooth muscle cell-mediated fibrosis without atherosclerosis.

BACKGROUNDDisease of the aorta varies from atherosclerosis to aneurysms, with complications including rupture, dissection, and poorly characterized limited tears. We studied limited tears without any mural hematoma, termed intimomedial tears, to gain insight into aortic vulnerability to excessive wall stresses. Our premise is that minimal injuries in aortas with sufficient medial resilience to prevent tear progression correspond to initial mechanisms leading to complete structural failure in aortas with significantly compromised medial resilience.METHODSIntimomedial tears were macroscopically identified in 9 of 108 ascending aortas after surgery and analyzed by histology and immunofluorescence confocal microscopy.RESULTSNonhemorrhagic, nonatheromatous tears correlated with advanced aneurysmal disease and most lacked distinctive symptoms or radiological signs. Tears traversed the intima and part of the subjacent media, while the resultant defects were partially or completely filled with neointima characterized by differentiated smooth muscle cells, scattered leukocytes, dense fibrosis, and absent elastic laminae despite tropoelastin synthesis. Healed lesions contained organized fibrin at tear edges without evidence of plasma and erythrocyte extravasation or lipid accumulation.CONCLUSIONThese findings suggest a multiphasic model of aortic wall failure in which primary lesions of intimomedial tears either heal if the media is sufficiently resilient or progress as dissection or rupture by medial delamination and tear completion, respectively. Moreover, mural incorporation of thrombus and cellular responses to injury, two historically important concepts in atheroma pathogenesis, contribute to vessel wall repair with adequate conduit function, but even together are not sufficient to induce atherosclerosis.FUNDINGNIH (R01-HL146723, R01-HL168473) and Yale Department of Surgery.

Deficiency of smooth muscle cell ILF3 alleviates intimal hyperplasia via HMGB1 mRNA degradation-mediated regulation of the STAT3/DUSP16 axis.

Intimal hyperplasia is a complicated pathophysiological phenomenon attributable to in-stent restenosis, and the underlying mechanism remains unclear. Interleukin enhancer-binding factor 3 (ILF3), a double-stranded RNA-binding protein involved in regulating mRNA stability, has been recently demonstrated to assume a crucial role in cardiovascular disease; nevertheless, its impact on intimal hyperplasia remains unknown. In current study, we used samples of human restenotic arteries and rodent models of intimal hyperplasia, we found that vascular smooth muscle cell (VSMC) ILF3 expression was markedly elevated in human restenotic arteries and murine ligated carotid arteries. SMC-specific ILF3 knockout mice significantly suppressed injury induced neointimal formation. In vitro, platelet-derived growth factor type BB (PDGF-BB) treatment elevated the level of VSMC ILF3 in a dose- and time-dependent manner. ILF3 silencing markedly inhibited PDGF-BB-induced phenotype switching, proliferation, and migration in VSMCs. Transcriptome sequencing and RNA immunoprecipitation sequencing depicted that ILF3 maintained its stability upon binding to the mRNA of the high-mobility group box 1 protein (HMGB1), thereby exerting an inhibitory effect on the transcription of dual specificity phosphatase 16 (DUSP16) through enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3). Therefore, the results both in vitro and in vivo indicated that the loss of ILF3 in VSMC ameliorated neointimal hyperplasia by regulating the STAT3/DUSP16 axis through the degradation of HMGB1 mRNA. Our findings revealed that vascular injury activates VSMC ILF3, which in turn promotes intima formation. Consequently, targeting specific VSMC ILF3 may present a potential therapeutic strategy for ameliorating cardiovascular restenosis.

Plasma S1P Orchestrates the Reverse Transendothelial Migration of Aortic Intimal Myeloid Cells in Mice.

BACKGROUND: Myeloid cells (MCs) reside in the aortic intima at regions predisposed to atherosclerosis. Systemic inflammation triggers reverse transendothelial migration (RTM) of intimal MCs into the arterial blood, which orchestrates a protective immune response that clears intracellular pathogens from the arterial intima. Molecular pathways that regulate RTM remain poorly understood. S1P (sphingosine-1-phosphate) is a lipid mediator that regulates immune cell trafficking by signaling via 5 G-protein-coupled receptors (S1PRs [S1P receptors]). We investigated the role of S1P in the RTM of aortic intimal MCs. METHODS: Intravenous injection of lipopolysaccharide was used to model a systemic inflammatory stimulus that triggers RTM. CD11c+ intimal MCs in the lesser curvature of the ascending aortic arch were enumerated by en face confocal microscopy. Local gene expression was evaluated by transcriptomic analysis of microdissected intimal cells. RESULTS: In wild-type C57BL/6 mice, lipopolysaccharide induced intimal cell expression of S1pr1, S1pr3, and Sphk1 (a kinase responsible for S1P production). Pharmacological modulation of multiple S1PRs blocked lipopolysaccharide-induced RTM and modulation of S1PR1 and S1PR3 reduced RTM in an additive manner. Cre-mediated deletion of S1pr1 in MCs blocked lipopolysaccharide-induced RTM, confirming a role for myeloid-specific S1PR1 signaling. Global or hematopoietic deficiency of Sphk1 reduced plasma S1P levels, the abundance of CD11c+ MCs in the aortic intima, and blunted lipopolysaccharide-induced RTM. In contrast, plasma S1P levels, the abundance of intimal MCs, and lipopolysaccharide-induced RTM were rescued in Sphk1-/- mice transplanted with Sphk1+/+ or mixed Sphk1+/+ and Sphk1-/- bone marrow. Stimulation with lipopolysaccharide increased endothelial permeability and intimal MC exposure to circulating factors such as S1P. CONCLUSIONS: Functional and expression studies support a novel role for S1P signaling in the regulation of lipopolysaccharide-induced RTM and the homeostatic maintenance of aortic intimal MCs. Our data provide insight into how circulating plasma mediators help orchestrate intimal MC dynamics.

A large post-stenting intramural hematoma in the left anterior descending artery caused by a small intimal calcium spur; should we respect the calcium shape?

Coronary heavy calcification (HC) poses a sturdy challenge to percutaneous coronary intervention (PCI). Scores considering calcification length, thickness, or circumferential extent, are widely accepted to dictate upfront calcium modification to improve PCI outcomes. Although often marginalized, calcification shape (morphology) may require consideration during procedure planning in selected cases. This case demonstrates how a focal but spur-shaped calcification led to a massive proximal left anterior descending (LAD) dissecting intramural hematoma.

Prognostic Implications of Initial Focal Contrast Enhancement in Acute Type B Intramural Hematoma.

BACKGROUND: The prognostic implication of initial focal contrast enhancement (FCE), including focal intimal disruption (FID) and intramural blood pool (IBP), in acute type B intramural hematoma (IMH) remain unclear. OBJECTIVES: The purpose of this study was to compare the prognostic implications in IMH with or without FCE. METHODS: A total of 574 patients were enrolled. FID was defined as an intimal disruption with contrast-filled out-pouching from the aorta lumen with a communicating orifice of >3 mm, and IBP was defined as a localized contrast medium-filled pool inside the IMH. RESULTS: A total of 207 (36.1%) patients with initial FCE, including 132 (63.8%) FIDs and 75 (36.2%) IBPs, were identified. Patients with FCE accompanying IMH were more likely to have hypertension (P = 0.001), pleural effusion (P = 0.006), fewer aortic segments involved (P < 0.001), more adverse aortic events (AAEs) (P < 0.001), and fewer freedom from intervention (P = 0.002). Pleural effusion (HR: 1.79; 95% CI: 1.25-2.55; P = 0.001) and FCE (HR: 1.51; 95% CI: 1.12-2.02; P = 0.006) were identified to be the independent risk factors of AAEs. In the subgroup analysis, IMH with initial FID were more likely to progress than those with initial IBP (P < 0.001). FIDs located at the proximal descending aorta (HR: 2.95; 95% CI: 1.65-5.29; P < 0.001) were associated with AAEs. CONCLUSIONS: Patients with FCE accompanying IMH were more likely to progress, especially in those initial FID localized at the proximal descending aorta. (Nature course and predictors of progression of intramural hematoma: A retrospective, multicenter study; ChiCTR2300073829).

Effect of F11 Receptor/Junctional Adhesion Molecule-A-derived Peptide on Neointimal Hyperplasia in a Murine Model.

PURPOSE: To determine whether inhibition of the F11 receptor/JAM-A (F11R) using F11R-specific antagonist peptide 4D results in inhibition of smooth muscle cell (SMC) proliferation and migration in vivo, known as neointimal hyperplasia (NIH), using a mouse focal carotid artery stenosis model (FCASM). MATERIALS AND METHODS: The mouse FCASM was chosen to test the hypothesis because the dominant cell type at the site of stenosis is SMC, similar to that in vascular access stenosis. Fourteen C57BL/6 mice underwent left carotid artery (LCA) partial ligation to induce stenosis, followed by daily injection of peptide 4D in 7 mice and saline in the remaining 7 mice, and these mice were observed for 21 days and then euthanized. Bilateral carotid arteries were excised for histologic analysis of the intima and media areas. RESULTS: The mean intimal area was significantly larger in control mice compared with peptide 4D-treated mice (0.031 mm2 [SD ± 0.024] vs 0.0082 mm2 [SD ± 0.0103]; P = .011). The mean intima-to-intima + media area ratio was significantly larger in control mice compared with peptide 4D-treated mice (0.27 [SD ± 0.13] vs 0.089 [SD ± 0.081]; P = .0079). NIH was not observed in the right carotid arteries in both groups. CONCLUSIONS: Peptide 4D, an F11R antagonist, significantly inhibited NIH in C57BL/6 mice in a FCASM.

Timing of Intervention and Long-Term Outcomes of Type B Aortic Intramural Hematoma with Intimal Disruption at Admission.

BACKGROUND: To compare the 30-day and long-term outcomes between patients with concomitant type B intramural hematoma and intimal disruption upon admission who underwent endovascular repair in the acute or subacute phases. METHODS: Data were extracted from January 1, 2010, to December 31, 2019. Logistic regression and Cox regression were performed to evaluate the impact of timing of intervention on 30-day and long-term outcomes, respectively. RESULTS: The study included 241 patients, among which 159 were in the acute group. No significant difference was observed in 30-day mortality (0.6% vs. 0%, P = 1), 30-day complication rate (2.5% vs. 1.2%, P = 0.664), long-term all-cause mortality (10.7% vs. 7.3%, P = 0.540), and aortic reintervention rate (2.5% vs. 2.4%, P = 1) between the acute and subacute group. In multivariable analysis, the timing of intervention was not associated with 30-day mortality (odds ratio (OR) = 0, 95% confidence interval CI: 0-Inf, P = 0.999), 30-day complication (OR = 0.30, 95% CI: 0.02-3.77, P = 0.348), long-term mortality (hazard ratio = 0.56, 95% CI: 0.20-1.61, P = 0.283), and aortic reintervention (OR = 0.97, 95% CI: 0.15-6.08, P = 0.970). CONCLUSIONS: For patients with concomitant type B intramural hematoma and intimal disruption upon admission, there is no significant difference in 30-day and long-term outcomes between those who undergo endovascular treatment in the acute or subacute phase.

Assessment of the aortic tunica media histological changes in relation with the cause of death.

AIM: The authors set out to evaluate the correlations between three of the main morphological aortic parameters (elastic fibers - FE, collagen fibers - FCOL, and smooth muscle fibers - FM) and the cause of death. MATERIALS AND METHODS: Study groups included 25 cases died of a vascular disease (V_P), 37 cases died of a non-vascular disease (NV_P) and 28 cases died of a violent/suspect non-pathological cause of death (V_Dth), the latter group representing also the control group. Four aortic cross-sections (base, arch, thoracic, and abdominal regions) were collected during autopsy from the selected cases, fixed in 10% buffered formalin and first of all photographed together with a calibrating ruler. Then, they were embedded in paraffin, sectioned off at 4 µm and stained with Hematoxylin-Eosin (HE) and Orcein. The obtained histological slides were transformed into virtual slides. Fibrillary components amounts were using a custom-made software, developed in MATLAB (MathWorks, USA). Statistical tools used were Pearson's correlation test, t-test (two-sample assuming equal variances) and one-way analysis of variance (ANOVA) test. RESULTS AND DISCUSSIONS: The amounts of the three fibrillary components of the aortic tunica media had a synchronous variation in all aortic regions in each of the three groups, excepting FCOL in the group of patients died from vascular pathology, which presented only a trend of synchronous variation along the aorta. FE had their lowest values and FCOL had their highest values in patients died from vascular pathology. FCOL had always higher levels than FE in people died from any pathological condition, vascular or non-vascular. FM had always at least two times lower level than that of the other types of fibers, regardless of whether the person died due to a pathological condition or not. CONCLUSIONS: The different pathological conditions causing death are influencing the fibrillary composition of aortic tunica media. Further studies are required to reveal other changes in the morphology of aortic wall in particular and vascular wall in general that could be related with different pathological conditions affecting the entire organism.

Unveiling the Hidden Landscape of Arterial Diseases at Single-Cell Resolution.

High-resolution single-cell technologies have shed light on the pathogenesis of cardiovascular diseases by enabling the discovery of novel cellular and transcriptomic signatures associated with various conditions, and uncovering new contributions of inflammatory processes, immunity, metabolic stress, and risk factors. We review the information obtained from studies using single-cell technologies in tissues with atherosclerosis and aortic aneurysms. Insights are provided on the biology of endothelial, smooth muscle, and immune cells in the arterial intima and media. In addition to cellular diversity, numerous examples of plasticity and phenotype switching are highlighted and presented in the context of normal cell functions.

A review on the treatment of intimal hyperplasia with perivascular medical devices: role of mechanical factors and drug release kinetics.

INTRODUCTION: Intimal hyperplasia (IH) is a significant factor limiting the success of revascularization surgery for blood flow restoration. IH results from a foreign body response and mechanical disparity that involves complex biochemical reactions resulting in graft failure. The available treatment option utilizes either different pharmacological interventions or mechanical support to the vascular grafts with limited success. AREAS COVERED: This review explains the pathophysiology of IH, responsible mechanical and biological factors, and treatment options, emphasizing perivascular devices. They are designed to provide mechanical support and pharmacology actions. The perivascular drug delivery concept has successfully demonstrated efficacy in various animal studies. Accurate projections of drug release mechanisms using mathematical modeling could be used to formulate prolonged drug elution devices. Numerical modeling aspects for the prediction of design outcomes have been given due importance that fulfills the unmet clinical need for better patient care. EXPERT OPINION: IH could be effectively prevented by simultaneous mechanical scaffolding and sustained local drug delivery. Future perivascular medical devices could be designed to integrate these essential features. Numerical modeling for device performance prediction should be utilized in the development of next-generation perivascular devices.

Aortic Intima-Media Thickness is Increased in Neonates of Mothers with Gestational Diabetes Mellitus: The Role of Thioredoxin-Interacting Protein as a Marker of Oxidative Stress.

BACKGROUND: Offspring exposed in foetal life to gestational diabetes mellitus (GDM) are at increased risk for future metabolic diseases. OBJECTIVE: To explore the prognostic role of abdominal aorta intima-media thickness (aIMT) in neonates exposed to GDM as a possible biomarker for later atherogenesis and its possible correlation with thioredoxin- interacting protein (TXNIP), a protein involved in oxidative stress. METHODS: In this prospective, observational study, mother-infant pairs were studied in 2 groups (57 patients with GDM and 51 controls without GDM). TXNIP levels were measured in the placenta, as well as in the umbilical and neonatal blood. The data were correlated with aIMT in neonates. RESULTS: aIMT was increased in GDM offspring (patients: median [range]=0.39 mm [0.31-0.46] vs controls: median=0.28 mm [0.23-0.33]; p=0.001) and remained significant after adjusting for possible confounders (e.g., triglycerides, blood pressure, vitamin D, birth weight and gender; ß coefficient=0.131 p=0.049). TXNIP levels were increased in trophoblasts (p=0.001) and syncytiotrophoblasts (p=0.001) and were decreased in endothelial cells (p=0.022) in GDM offspring vs controls. Moreover, TXNIP levels in trophoblasts positively correlated with aIMT (r=0.369; p=0.001). TXNIP levels in umbilical/ neonatal blood were not associated with GDM. CONCLUSION: Increased aIMT was demonstrated in the offspring of mothers with GDM. Non-invasive measurement of aIMT could be used as a biomarker to identify children at increased risk for atherogenesis later in life. This information may encourage early preventive measures. TXNIP may be associated with GDM and/or aIMT.

A nonobstructive condition: Medial arterial calcification. / ä¸å¼•èµ·ç®¡è ”ç‹­çª„çš„è¡€ç®¡ä¸­è†œé’™åŒ–.

Vascular calcification, including intimal and medial calcification, is closely associated with a significant increase in cardiovascular diseases. Although increased understandings were achieved, people still know much more about intimal calcification than medial calcification because the latter doesn't obstruct the arterial lumen, commonly considered as a non-significant finding. We clarified the pathologic characteristic of medial calcification, its difference from intimal calcification, principally focused on its clinical relevance, such as diagnosis, nosogenesis, and hemodynamics. We underline the importance of identifying and distinguishing medial calcification, understanding its effect to local/systematic arterial compliance, and relationship to diabetic neuropathy. Recent studies emphasize do not ignore its predictive role in cardiovascular mortality. It is of great clinical significance to summarize the mechanisms of occurrence, lesion characteristics, diagnostic methods, pathogenic mechanisms, hemodynamic changes, and the distinction as well as association of intimal calcification with intimal calcification.

The Role of TGF-ß Signaling in Saphenous Vein Graft Failure after Peripheral Arterial Disease Bypass Surgery.

Saphenous vein bypass grafting is an effective technique used to treat peripheral arterial disease (PAD). However, restenosis is the major clinical challenge for the graft vessel among people with PAD postoperation. We hypothesize that there is a common culprit behind arterial occlusion and graft restenosis. To investigate this hypothesis, we found TGF-ß, a gene specifically upregulated in PAD arteries, by bioinformatics analysis. TGF-ß has a wide range of biological activities and plays an important role in vascular remodeling. We discuss the molecular pathway of TGF-ß and elucidate its mechanism in vascular remodeling and intimal hyperplasia, including EMT, extracellular matrix deposition, and fibrosis, which are the important pathways contributing to stenosis. Additionally, we present a case report of a patient with graft restenosis linked to the TGF-ß pathway. Finally, we discuss the potential applications of targeting the TGF-ß pathway in the clinic to improve the long-term patency of vein grafts.

Multilineage commitment of Sca-1+ cells in reshaping vein grafts.

Vein graft failure remains a significant clinical problem. Similar to other vascular diseases, stenosis of vein grafts is caused by several cell lines; however, the sources of these cells remain unclear. The objective of this study was to investigate the cellular sources that reshape vein grafts. By analyzing transcriptomics data and constructing inducible lineage-tracing mouse models, we investigated the cellular components of vein grafts and their fates. The sc-RNAseq data suggested that Sca-1+ cells were vital players in vein grafts and might serve as progenitors for multilineage commitment. By generating a vein graft model in which the venae cavae from C57BL/6J wild-type mice were transplanted adjacent to the carotid arteries of Sca-1(Ly6a)-CreERT2; Rosa26-tdTomato mice, we demonstrated that the recipient Sca-1+ cells dominated reendothelialization and the formation of adventitial microvessels, especially at the perianastomotic regions. In turn, using chimeric mouse models, we confirmed that the Sca-1+ cells that participated in reendothelialization and the formation of adventitial microvessels all had a non-bone-marrow origin, whereas bone-marrow-derived Sca-1+ cells differentiated into inflammatory cells in vein grafts. Furthermore, using a parabiosis mouse model, we confirmed that non-bone-marrow-derived circulatory Sca-1+ cells were vital for the formation of adventitial microvessels, whereas Sca-1+ cells derived from local carotid arteries were the source of endothelium restoration. Using another mouse model in which venae cavae from Sca-1 (Ly6a)-CreERT2; Rosa26-tdTomato mice were transplanted adjacent to the carotid arteries of C57BL/6J wild-type mice, we confirmed that the donor Sca-1+ cells were mainly responsible for smooth muscle cells commitment in the neointima, particularly at the middle bodies of vein grafts. In addition, we provided evidence that knockdown/knockout of Pdgfrα in Sca-1+ cells decreased the cell potential to generate SMCs in vitro and decreased number of intimal SMCs in vein grafts. Our findings provided cell atlases of vein grafts, which demonstrated that recipient carotid arteries, donor veins, non-bone-marrow circulation, and the bone marrow provided diverse Sca-1+ cells/progenitors that participated in the reshaping of vein grafts.

A rare presentation of Sintilimab-induced swelling along the vessels: Case report.

RATIONALE: Immune-related adverse events are occasionally reported in Sintilimab treatment. This study reports a forward and reverse swelling case along the vein after infusion of Sintilimab. At present, swelling along the vascular direction during peripheral infusion are limitedly reported at home and abroad, especially when choosing a vein with thick, elastic, and good blood return. PATIENT CONCERNS: A 56-year-old male who suffered from esophageal cancer and liver cancer and received albumin-bound paclitaxel and nedaplatin chemotherapy in combination with Sintilimab immunotherapy appeared swelling along the vessel after infusion of Sintilimab. The patient was punctured 3 times. DIAGNOSES: Sintilimab-induced vascular edema may be a side effect resulted from a combination of variables such as relatively poor vascular function of the patient, chemical extravasation, allergic skin reactions, venous valves, vascular intima, and diameter stenosis. Sintilimab rarely causes vascular edema only when drug allergic reaction is the underlying factor. As only a few cases of vascular edema caused by Sintilimab have been reported, causes to such a drug-induced vascular edema remained unclear. INTERVENTIONS: The swelling was controlled by an intravenous specialist nurse according to delayed extravasation treatment and the doctor anti-allergy treatment, but the uncertainty of repeated puncture and symptom diagnosis caused pain and anxiety to the patient and his family. OUTCOMES: The symptom of swelling was gradually relieved after the anti-allergic treatment. The patient completed the following drug infusion without discomfort after the third puncture. When the patient was discharged the next day, swelling in his both hands disappeared, and the patient had no anxiety or discomfort. LESSONS: The side effects of immunotherapy may accumulate over time. Early identification and appropriate nursing management are the keys to minimizing patients' pain and anxiety. To effectively treat symptoms, nurses could benefit from quickly identifying the source of swelling.