Volume-Outcome Relationships for Intra-Aortic Balloon Pump in Acute Myocardial Infarction.

BACKGROUND: Acute myocardial infarction (AMI) is a major scenario for the use of an intra-aortic balloon pump (IABP), particularly when complicated by cardiogenic shock, although the utilization of mechanical circulatory support devices varies widely per hospital. We evaluated the relationship, at the hospital level, between the volume of IABP use and mortality in AMI.Methods and Results: Using a Japanese nationwide administrative database, 26,490 patients with AMI undergoing primary percutaneous coronary intervention (PCI) from 154 hospitals were included in this study. The primary endpoint was the observed-to-predicted in-hospital mortality ratio. Predicted mortality per patient was calculated using baseline variables and averaged for each hospital. The associations among PCI volume for AMI, observed and predicted in-hospital mortality, and observed and predicted IABP use were assessed per hospital. Of 26,490 patients, 2,959 (11.2%) were treated with IABP and 1,283 (4.8%) died during hospitalization. The annualized number of uses of IABP per hospital in AMI was 4.5. In lower-volume primary PCI centers, IABP was more likely to be underused than expected, and the observed-to-predicted in-hospital mortality ratio was higher than in higher-volume centers. CONCLUSIONS: A lower annual number of IABP use was associated with an increased mortality risk at the hospital level, suggesting that IABP use can be an institutional quality indicator in the setting of AMI.

Association between the quantity of stroke care units and the complement of neurosurgical and neurology specialists in Japan: A retrospective study.

BACKGROUND: Stroke care units provide advanced intensive care for unstable patients with acute stroke. We conducted a survey to clarify the differences in stroke care units between urban and regional cities and the relationship between the number of stroke care unit beds and neurologists. METHODS: This retrospective observational study was conducted in 2,857 and 4,184 hospitals in urban and regional cities in 47 provinces of Japan, respectively, between January 2020 and August 2023. Tokyo and ordinance-designated cities in provinces were defined as urban cities, and those without such cities were defined as regional cities. The primary endpoint was the presence or absence of a stroke care unit. RESULTS: Multiple linear regression analysis revealed that the presence of stroke care units was significantly associated with the number of neurosurgical specialists. Receiver operating characteristic curve analysis was performed to predict the number of personnel required for stroke care unit installation based on the number of neurosurgical specialists. The area under the receiver operating characteristic curve, Youden index, sensitivity, and specificity were 0.721, 0.483, 0.783, and 0.700, respectively. CONCLUSIONS: Our study underscores the indispensability of SCUs in stroke treatment, advocating for a strategic allocation of medical resources, heightened accessibility to neurosurgical specialists, and a concerted effort to address geographic and resource imbalances. The identified cutoff value of 8.99 neurosurgical specialists per 100,000 population serves as a practical benchmark for optimizing SCU establishment, thereby potentially mitigating stroke-related mortality.

Effect of admission in the stroke care unit versus intensive care unit on in-hospital mortality in patients with acute ischemic stroke.

BACKGROUND/OBJECTIVE: Few reports have directly compared the outcomes of patients with acute ischemic stroke (AIS) who are managed in a stroke care unit (SCU) with those who are managed in an intensive care units (ICU). This large database study in Japan aimed to compare in-hospital mortality between patients with AIS admitted into SCU and those admitted into ICU. METHODS: Patients with AIS who were admitted between April 1, 2014, and March 31, 2019, were selected from the administrative database and divided into the SCU and ICU groups. We calculated the propensity score to match groups for which the admission unit assignment was independent of confounding factors, including the modified Rankin scale (mRS) score. The primary outcome was in-hospital mortality, and secondary outcomes were the mRS score at discharge, length of stay (LOS), and total hospitalization cost. RESULTS: Overall, 8,683 patients were included, and 960 pairs were matched. After matching, the in-hospital mortality rates of the SCU and ICU groups were not significantly different (5.9% vs. 7.9%, P = 0.106). LOS was significantly shorter (SCU = 20.9 vs. ICU = 26.2 days, P < 0.001) and expenses were significantly lower in the SCU group than in the ICU group (SCU = 1,686,588 vs. ICU = 1,998,260 yen, P < 0.001). mRS scores (score of 1-3 or 4-6) at discharge were not significantly different after matching. Stratified analysis showed that the in-hospital mortality rate was lower in the ICU group than in the SCU group among patients who underwent thrombectomy. CONCLUSIONS: In-hospital mortality was not significantly different between the ICU and SCU groups, with significantly lower costs and shorter LOS in the SCU group than in the ICU group.

Novel myocardial markers GADD45G and NDUFS5 identified by RNA-sequencing predicts left ventricular reverse remodeling in advanced non-ischemic heart failure: a retrospective cohort study.

BACKGROUND: Left ventricular reverse remodeling (LVRR) has been detected in non-ischemic dilated cardiomyopathy (NIDCM) patients following optimal treatment. However, its prediction with only conventional modalities is often difficult. This study sought to examine whether RNA sequencing (RNA-seq) of myocardium tissue samples could predict LVRR in NIDCM. METHODS: A total of 17 advanced NIDCM patients with left ventricular ejection fraction (LVEF) below 30% who underwent cardiac biopsy from Left ventricle (LV) were prospectively recruited. They received optimal treatment and followed with echocardiogram every 6 months. Based on LVRR status after 12 months of treatment, patients were divided into the reverse remodeling (RR) or non-RR group. Tissue samples were analyzed by RNA-seq, and a functional analysis of differentially expressed genes was carried out. RESULTS: There were eight and nine patients in the RR and non-RR groups, respectively. No difference was found in age, sex, disease duration, LV end-diastolic diameter, and LVEF between the two groups. There were 155 genes that were differentially expressed between the two groups. Nicotinamide adenine dinucleotide ubiquinone oxidoreductase subunit (NDUF)S5 and Growth arrest and DNA-damage-inducible protein (GADD)45G, along with several genes related to the mitochondrial respiratory chain and ribosome, were significantly downregulated in the RR as compared to the non-RR group. CONCLUSION: GADD45G and NDUFS5 are potential biomarkers for LVRR in patients with advanced NIDCM.

Regeneration of the Cardiac Conduction System by Adipose Tissue-Derived Stem Cells.

BACKGROUND: Adipose tissue is one of the sources of mesenchymal stem cells, which have the potential to differentiate into various types of cells, including myocytes. Whether brown adipose tissue (BAT)-derived cells might differentiate into the cardiac pacemaking-conducting cells, and have the potential to regenerate the cardiac conduction system (CCS), is investigated in this study. METHODS AND RESULTS: BAT was isolated from the interscapular area of mice and enzymatically digested before culture. Round or fusiform cells showed spontaneous beating at 4-7 days after culturing of BAT-derived cells. Reverse transcriptase-polymerase chain reaction analysis and immunocytochemical analysis revealed that BAT-derived cells expressed several cardiomyocytes, the CCS and pacemaker (PM) cell marker genes and proteins. Patch-clamp techniques revealed that spontaneous electrical activity and the shape of the action potential showed properties of cardiac PM cells. Next, a complete atrioventricular (AV) block was created in mice and green fluorescent protein-positive (GFP (+)) BAT-derived cells were injected intramyocardially around the AV node. At 1 week after transplantation, 50% of BAT-derived cells injected mice showed a sinus rhythm or a 2:1 AV block. Immunohistochemical analysis revealed that injected GFP (+) cells were engrafted and some GFP (+) cells co-expressed several cardiac PM cell marker proteins. CONCLUSIONS: BAT-derived cells differentiate into the CCS and PM-like cells in vitro and in vivo, and may become a useful cell source for arrhythmia therapy.

Factors affecting the length of hospital stay for total knee arthroplasty in Japan: a retrospective study using the diagnosis procedure combination database.

BACKGROUND: We aimed to evaluate the length of hospital stay following total knee arthroplasty to determine the impact of relevant factors using data from the Diagnosis Procedure Combination database. METHODS: This was a retrospective observational study. The study cohort included 5,831 patients who had osteoarthritis of the knee and had undergone total knee replacement between February 2018 and October 2022 at 38 hospitals. RESULTS: Multivariate analysis showed that the factors influencing the length of stay included: age (p < 0.001), height (p < 0.001), weight (p = 0.049), body mass index (p = 0.008), Barthel index (p < 0.001), method of anesthesia (p < 0.001), bone transplant (p = 0.010), timing of postoperative rehabilitation (p < 0.001), atrial fibrillation (p < 0.001), chronic pain (p < 0.001), and number of institutionally treated cases (p < 0.001) (r = 0.451, p < 0.001). CONCLUSIONS: Shorter or longer hospital stays were found to be associated with the patients' background characteristics and facility-specific factors; these can lead to more accurate estimates of the length of hospital stay and appropriate allocation of resources.

Volume-outcome relationships for extracorporeal membrane oxygenation in acute myocardial infarction.

Acute myocardial infarction (MI) is one of the major scenarios of extracorporeal membrane oxygenation (ECMO) use. The utilization of mechanical circulatory support systems including ECMO varies widely at the hospital level, while whether ECMO volume per hospital is associated with outcomes in acute MI is unclear. Using a Japanese nationwide administrative database, a total of 26,913 patients with acute MI undergoing percutaneous coronary intervention from 154 hospitals were included. The relations among PCI volume for acute MI, observed and predicted in-hospital mortality, and observed and predicted rates of ECMO use were evaluated at the hospital level. Of 26,913 patients, 423 (1.6%) were treated with ECMO, and 1561 (5.8%) died during the hospitalization. Median ECMO use per hospital per year was 0.5. An observed rate of ECMO use was linearly correlated with the predicted probability of ECMO use and was not associated with the observed/predicted in-hospital mortality ratio. The observed/predicted mortality ratio was lowest in hospitals with the observed/predicted ECMO use ratio of around one. In conclusion, ECMO was infrequently used in a setting of acute MI at each hospital annually. An observed rate of ECMO use was not associated with observed/predicted in-hospital mortality ratio, while the observed/predicted in-hospital mortality ratio was lowest when ECMO was used as predicted, suggesting that standardized ECMO use may be an institutional quality indicator in acute MI.

Regional variation in the use of revascularisation for peripheral artery disease in Japan: a cross-sectional observational study.

OBJECTIVES: We aimed to investigate the regional variations in the number of interventions and surgeries for peripheral artery disease (PAD) and explore the major determinants of the variations. DESIGN: Cross-sectional study. SETTING: The Japanese Ministry of Health, Labour and Welfare National Database and Diagnostic Procedure Combination database in 2018. DATA: The rates of endovascular treatment (EVT), bypass surgery per 100 000 individuals in the population were calculated for all 47 prefectures in Japan. The total annual changes in the rates of EVT and bypass surgery in Japan from 2012 to 2019 were calculated. ANALYSIS: A linear regression model was developed with rates of EVT and bypass surgery as dependent variables and regional medical supply in each prefecture as explanatory variables. These regional factors included the rate of percutaneous coronary intervention (PCI) for angina, the numbers of cardiovascular specialists, specialists in cardiac surgery, interventional radiology (IVR) training facilities and cardiovascular surgery training facilities, per 100 000, respectively. RESULTS: There was a 5.7-fold difference (143 and 25 per 100 000 individuals aged ≥40 years) in the highest and lowest EVT rates. The highest and lowest rates of bypass surgery were 34 and <10 per 100 000 individuals aged ≥40 years in a prefecture, respectively. The rate of PCI contributed most significantly positive to the rate of EVT (p<0.001). However, the numbers of IVR and cardiovascular surgery training facilities had significant positive and negative relationships, respectively, with the rate of EVT. The numbers of specialists in cardiac surgery and cardiovascular specialists had significant positive (p=0.01) and negative (p=0.01) correlations, respectively, with the rate of bypass surgery. CONCLUSIONS: Considerable regional variations in the rates of revascularisation for PAD were found. Unbalanced presence of medical resources, preference of suppliers and the training system had larger effects on the regional variation in Japan.

Pericardial Grafting of Cardiac Progenitor Cells in Self-Assembling Peptide Scaffold Improves Cardiac Function After Myocardial Infarction.

Many studies have explored cardiac progenitor cell (CPC) therapy for heart disease. However, optimal scaffolds are needed to ensure the engraftment of transplanted cells. We produced a three-dimensional hydrogel scaffold (CPC-PRGmx) in which high-viability CPCs were cultured for up to 8 weeks. CPC-PRGmx contained an RGD peptide-conjugated self-assembling peptide with insulin-like growth factor-1 (IGF-1). Immediately after creating myocardial infarction (MI), we transplanted CPC-PRGmx into the pericardial space on to the surface of the MI area. Four weeks after transplantation, red fluorescent protein-expressing CPCs and in situ hybridization analysis in sex-mismatched transplantations revealed the engraftment of CPCs in the transplanted scaffold (which was cellularized with host cells). The average scar area of the CPC-PRGmx-treated group was significantly smaller than that of the non-treated group (CPC-PRGmx-treated group = 46 ± 5.1%, non-treated MI group = 59 ± 4.5%; p < 0.05). Echocardiography showed that the transplantation of CPC-PRGmx improved cardiac function and attenuated cardiac remodeling after MI. The transplantation of CPCs-PRGmx promoted angiogenesis and inhibited apoptosis, compared to the untreated MI group. CPCs-PRGmx secreted more vascular endothelial growth factor than CPCs cultured on two-dimensional dishes. Genetic fate mapping revealed that CPC-PRGmx-treated mice had more regenerated cardiomyocytes than non-treated mice in the MI area (CPC-PRGmx-treated group = 0.98 ± 0.25%, non-treated MI group = 0.25 ± 0.04%; p < 0.05). Our findings reveal the therapeutic potential of epicardial-transplanted CPC-PRGmx. Its beneficial effects may be mediated by sustainable cell viability, paracrine function, and the enhancement of de novo cardiomyogenesis.

Volume-Outcome Relationships for Percutaneous Coronary Intervention in Acute Myocardial Infarction.

Background Lower primary percutaneous coronary intervention (PCI) volume is known to be associated with worse outcomes in patients with acute myocardial infarction (MI) at hospital level. The present study aimed to evaluate the relations of primary, elective, and total PCI volume and primary/total PCI volume ratio per hospital to in-hospital mortality in patients with acute MI undergoing primary PCI. Methods and Results Using a large nationwide administrative database, we included a total of 83 076 patients from 154 hospitals in Japan undergoing PCI for either acute MI or elective cases. Relations of annual procedural volumes for primary, elective, and total PCI to in-hospital mortality after acute MI at hospital level were evaluated. The ratio of primary to total PCI volume per hospital was also assessed. The primary end point was the ratio of observed to predicted mortality. Of 83 076 patients, 26 913 (32.4%) underwent primary PCI for acute MI, among whom 1561 (5.8%) died during hospitalization. Overall, observed in-hospital mortality after acute MI and observed/predicted mortality ratio were higher in hospitals with lower primary, elective, and total PCI volumes. Observed/predicted in-hospital mortality ratio was higher in hospitals with low primary/total PCI volume ratio, even in those with high total PCI volume. Conclusions Primary, elective, and total PCI volume at hospitals were inversely associated with in-hospital mortality in patients with acute MI undergoing primary PCI. Lower ratio of primary to total PCI volume were related to higher in-hospital mortality, suggesting primary/total PCI volume ratio as an institutional indicator of quality of care for acute MI.

Anagrelide-associated Cardiomyopathy and Heart Failure in a Patient with Essential Thrombocythemia: A Case Report and Literature Review.

Anagrelide is used worldwide to treat essential thrombocythemia (ET) by reducing platelet counts. Cardiomyopathy and heart failure (HF) are rare but serious complications associated with anagrelide use, although no cases were reported during Japanese Phase I to III studies. A 46-year-old, otherwise healthy, Japanese ET patient developed HF with reduced ejection fraction after 18 months of treatment with 1.0-3.5 mg of anagrelide daily. HF was stabilized with anagrelide withdrawal and guideline-directed HF therapy. The cardiac function returned to normal after six months. This case suggests that anagrelide can cause cardiomyopathy and HF in ET patients, regardless of nationality, comorbid cardiovascular conditions, or therapy duration.

Association between early intensive care or coronary care unit admission and post-discharge performance of activities of daily living in patients with acute decompensated heart failure.

The management of acute decompensated heart failure often requires intensive care. However, the effects of early intensive care unit/coronary care unit admission on activities of daily living (ADL) in acute decompensated heart failure patients have not been precisely evaluated. Thus, we retrospectively assessed the association between early intensive care unit admission and post-discharge ADL performance in these patients. Acute decompensated heart failure patients (New York Heart Association I-III) admitted on emergency between April 1, 2014, and December 31, 2018, were selected from the Diagnosis Procedure Combination database and divided into intensive care unit/coronary care unit (ICU) and general ward (GW) groups according to the hospitalization type on admission day 1. The propensity score was calculated to create matched cohorts where admission style (intensive care unit/coronary care unit admission) was independent of measured baseline confounding factors, including ADL at admission. The primary outcome was ADL performance level at discharge (post-ADL) defined according to the Barthel index. Secondary outcomes included length of stay and total hospitalization cost (expense). Overall, 12231 patients were eligible, and propensity score matching created 2985 pairs. After matching, post-ADL was significantly higher in the ICU group than in the GW group [mean (standard deviation), GW vs. ICU: 71.5 (35.3) vs. 78.2 (31.2) points, P<0.001; mean difference: 6.7 (95% confidence interval, 5.1-8.4) points]. After matching, length of stay was significantly shorter and expenses were significantly higher in the ICU group than in the GW group. Stratified analysis showed that the patients with low ADL at admission (Barthel index score <60) were the most benefited from early intensive care unit/coronary care unit admission. Thus, early intensive care unit/coronary care unit admission was associated with improved post-ADL in patients with emergency acute decompensated heart failure admission.

Implantation of cardiac progenitor cells using self-assembling peptide improves cardiac function after myocardial infarction.

Implantation of various types of cells into the heart has been reported to be effective for heart failure, however, it is unknown what kinds of cells are most suitable for myocardial repair. To examine which types of cells are most effective, we injected cell-Puramatrix™ (PM) complex into the border area and overlaid the cell-PM patch on the myocardial infarction (MI) area. We compared cardiac morphology and function at 2 weeks after transplantation. Among clonal stem cell antigen-1 positive cardiac progenitors with PM (cSca-1/PM), bone marrow mononuclear cells with PM (BM/PM), skeletal myoblasts with PM (SM/PM), adipose tissue-derived mesenchymal cells with PM (AMC/PM), PM alone (PM), and non-treated MI group (MI), the infarct area of cSca-1/PM was smaller than that of BM/PM, SM/PM, PM and MI. cSca-1/PM and AMC/PM attenuated ventricular enlargement and restored cardiac function in comparison with MI. Capillary density in the infarct area of cSca-1/PM was higher than that of other five groups. The percentage of TUNEL positive cardiomyocytes in the infarct area of cSca-1/PM was lower than that of MI and PM. cSca-1 secreted VEGF and some of them differentiated into cardiomyocytes and vascular smooth muscle cells. These results suggest that transplantation of cSca-1/PM most effectively prevents cardiac remodeling and dysfunction through angiogenesis, inhibition of apoptosis and myocardial regeneration.

Feasibility of management of hemodynamically stable patients with acute myocardial infarction following primary percutaneous coronary intervention in the general ward settings.

BACKGROUND: Although current guidelines recommend admission to the intensive/coronary care unit (ICU/CCU) for patients with ST-segment elevation myocardial infarction (MI), routine use of the CCU in uncomplicated patients with acute MI remains controversial. We aimed to evaluate the safety of management in the general ward (GW) of hemodynamically stable patients with acute MI after primary percutaneous coronary intervention (PCI). METHODS: Using a large nationwide administrative database, a cohort of 19426 patients diagnosed with acute MI in 52 hospitals where a CCU was available were retrospectively analyzed. Patients with mechanical cardiac support and Killip classification 4, and those without primary PCI on admission were excluded. A total of 5736 patients were included and divided into the CCU (n = 3488) and GW (n = 2248) groups according to the type of hospitalization room after primary PCI. Propensity score matching was performed, and 1644 pairs were matched. The primary endpoint was in-hospital mortality at 30 days. RESULTS: The CCU group had a higher rate of Killip classification 3 and ambulance use than the GW group. There was no significant difference in the incidence of in-hospital mortality within 30 days among the matched subjects. Multivariable Cox proportional hazard model analysis among unmatched patients supported the findings (hazard ratio 1.12, 95% confidence interval 0.66-1.91, p = 0.67). CONCLUSIONS: The use of the GW was not associated with higher in-hospital mortality in hemodynamically stable patients with acute MI after primary PCI. It may be feasible for the selected patients to be directly admitted to the GW after primary PCI.

Leukemia Inhibitory Factor Enhances Endogenous Cardiomyocyte Regeneration after Myocardial Infarction.

Cardiac stem cells or precursor cells regenerate cardiomyocytes; however, the mechanism underlying this effect remains unclear. We generated CreLacZ mice in which more than 99.9% of the cardiomyocytes in the left ventricular field were positive for 5-bromo-4-chloro-3-indolyl-ß-d-galactoside (X-gal) staining immediately after tamoxifen injection. Three months after myocardial infarction (MI), the MI mice had more X-gal-negative (newly generated) cells than the control mice (3.04 ± 0.38/mm2, MI; 0.47 ± 0.16/mm2, sham; p < 0.05). The cardiac side population (CSP) cell fraction contained label-retaining cells, which differentiated into X-gal-negative cardiomyocytes after MI. We injected a leukemia inhibitory factor (LIF)-expression construct at the time of MI and identified a significant functional improvement in the LIF-treated group. At 1 month after MI, in the MI border and scar area, the LIF-injected mice had 31.41 ± 5.83 X-gal-negative cardiomyocytes/mm2, whereas the control mice had 12.34 ± 2.56 X-gal-negative cardiomyocytes/mm2 (p < 0.05). Using 5-ethynyl-2'-deoxyurinide (EdU) administration after MI, the percentages of EdU-positive CSP cells in the LIF-treated and control mice were 29.4 ± 2.7% and 10.6 ± 3.7%, respectively, which suggests that LIF influenced CSP proliferation. Moreover, LIF activated the Janus kinase (JAK)signal transducer and activator of transcription (STAT), mitogen-activated protein kinase/extracellular signal-regulated (MEK)extracellular signal-regulated kinase (ERK), and phosphatidylinositol 3-kinase (PI3K)-AKT pathways in CSPs in vivo and in vitro. The enhanced green fluorescent protein (EGFP)-bone marrow-chimeric CreLacZ mouse results indicated that LIF did not stimulate cardiogenesis via circulating bone marrow-derived cells during the 4 weeks following MI. Thus, LIF stimulates, in part, stem cell-derived cardiomyocyte regeneration by activating cardiac stem or precursor cells. This approach may represent a novel therapeutic strategy for cardiogenesis.

An Abiotic Glass-Bead Collector Exhibiting Active Transport.

Animals relocate objects as needed by active motion. Active transport is ubiquitous in living organisms but has been difficult to realize in abiotic systems. Here we show that a self-propelled droplet can gather scattered beads toward one place on a floor and sweep it clean. This is a biomimetic active transport with loadings and unloadings, because the transport was performed by a carrier and the motion of the carrier was maintained by the energy of the chemical reaction. The oil droplet produced fluctuation of the local number density of the beads on the floor, followed by its autocatalytic growth. This mechanism may inspire the technologies based on active transport wherein chemical and physical substances migrate as in living organisms.

Anti-inflammatory peptides from cardiac progenitors ameliorate dysfunction after myocardial infarction.

BACKGROUND: Cardiac cell therapy has been proposed as one of the new strategies against myocardial infarction. Although several reports showed improvement of the function of ischemic heart, the effects of cell therapy vary among the studies and the mechanisms of the beneficial effects are still unknown. Previously, we reported that clonal stem cell antigen-1-positive cardiac progenitor cells exerted a therapeutic effect when transplanted into the ischemic heart. Our aims were to identify the cardiac progenitor-specific paracrine factor and to elucidate the mechanism of its beneficial effect. METHODS AND RESULTS: By using an antibody array, we found that soluble junctional adhesion molecule-A (JAM-A) was abundantly secreted from cardiac progenitor cells. Pretreatment of neutrophils with conditioned medium from cultured cardiac progenitor cells or soluble JAM-A inhibited transendothelial migration and reduced motility of neutrophils. These inhibitory effects were attenuated by anti-JAM-A neutralizing antibody. Injection of cardiac progenitor cells into infarct heart attenuated neutrophil infiltration and expression of inflammatory cytokines. Injection of soluble JAM-A-expressing, but not of JAM-A siRNA-expressing, cardiac progenitor cells into the infarct heart prevented cardiac remodeling and reduced fibrosis area. CONCLUSIONS: Soluble JAM-A secreted from cardiac progenitor cells reduces infiltration of neutrophils after myocardial infarction and ameliorates tissue damage through prevention of excess inflammation. Our finding may lead to a new therapy for cardiovascular disease by using the anti-inflammatory effect of JAM-A.