Lethal hemopericardium caused by infection of mitral annular calcification: An autopsy case report.

Mitral annular calcification (MAC) is a chronic and degenerative condition involving calcification of the mitral annulus. MAC is a risk factor for coronary artery disease, cardiovascular events, stroke, and cardiovascular death. However, patients with MAC are often asymptomatic. Herein, we present the first case of cardiac tamponade due to infection of MAC in forensic pathology. An 80-year-old woman was found in cardiopulmonary arrest shortly after experiencing fatigue. She was transferred to a hospital, and despite chest compression and ventilation, she was pronounced dead due to no response. Postmortem computed tomography, autopsy, and histological examination showed MAC, abscess formation involving Gram-positive cocci on the MAC, and fistulation of the abscess into the intracardial pericardial cavities, resulting in a massive lethal hemopericardium.

Can right ventricular endomyocardial biopsy predict left ventricular fibrosis beforehand in dilated cardiomyopathy?

AIMS: Myocardial fibrosis of the left ventricle (LV) is a prognostic factor in dilated cardiomyopathy (DCM). This study aims to evaluate whether fibrosis of right ventricular (RV) endomyocardial biopsy (EMB) can predict the degree of LV fibrosis beforehand in DCM. METHODS AND RESULTS: Fibrosis extent in 70 RV-EMB specimens of DCM diagnosis was compared with that in the whole cross-sectional LV of excised hearts in the same patients (52 explanted hearts for transplant and 18 autopsied hearts). The median interval between biopsy and excision was 4.1 (0.13-19.3) years. The fibrosis area ratio of the EMBs and excised hearts were evaluated via image analysis. The distribution of cardiovascular magnetic resonance-late gadolinium enhancement (LGE) in the intraventricular septum was classified into four quartile categories. The fibrosis area ratio in RV-EMB correlated significantly with that in the short-axis cut of the LV of excised hearts (r = 0.82, P < 0.0001) and with a diffuse pattern of LGE (r = 0.71, P = 0.003). In a multivariate model, after adjusting for the interval between biopsy performance and heart excision, the fibrosis area ratio in RV-EMB was associated with that in LV-excised heart (regression coefficient, 0.82; 95% confidence interval, 0.68-0.95; P < 0.0001). CONCLUSIONS: The fibrosis observed in RV-EMB positively correlated with the extent of fibrosis in the LV of excised hearts in patients with DCM. The study findings may help predict LV fibrosis, considered a prognostic factor of DCM through relatively accessible biopsy techniques.

Case Report: Molecular autopsy underlie COVID-19-associated sudden, unexplained child mortality.

Herein, we report a child with COVID-19 and seemingly no underlying disease, who died suddenly. The autopsy revealed severe anemia and thrombocytopenia, splenomegaly, hypercytokinemia, and a rare ectopic congenital coronary origin. Immunohistochemical analysis demonstrated that the patient had acute lymphoblastic leukemia of the B-cell precursor phenotype (BCP-ALL). The complex cardiac and hematological abnormalities suggested the presence of an underlying disease; therefore, we performed whole-exome sequencing (WES). WES revealed a leucine-zipper-like transcription regulator 1 (LZTR1) variant, indicating Noonan syndrome (NS). Therefore, we concluded that the patient had underlying NS along with coronary artery malformation and that COVID-19 infection may have triggered the sudden cardiac death due to increased cardiac load caused by high fever and dehydration. In addition, multiple organ failure due to hypercytokinemia probably contributed to the patient's death. This case would be of interest to pathologists and pediatricians because of the limited number of NS patients with LZTR1 variants; the complex combination of an LZTR1 variant, BCP-ALL, and COVID-19; and a rare pattern of the anomalous origin of the coronary artery. Thus, we highlight the significance of molecular autopsy and the application of WES with conventional diagnostic methods.

An unusual case of fatal hypothermia involving topical diphenhydramine.

PURPOSE: Diphenhydramine is an antihistamine drug widely used to alleviate symptoms caused by allergies and the common cold. Diphenhydramine-involved fatalities have been reported in the past but usually involving overdose by ingestion. We report a peculiar case of fatal hypothermia during non-winter season involving topical diphenhydramine. METHODS: A 23-year-old male with no known preexisting medical conditions was found dead in the bathroom of his apartment with a small amount of running water on his back. Postmortem examinations and toxicological analysis on blood and urine were performed. RESULTS: Color difference was apparent between the right and left cardiac blood. Wischnewski spots were observed in the gastric mucosa. Histological examination revealed no obvious findings that could attribute to serious cardiovascular events. Drug screening by gas chromatograph-tandem mass spectrometry (GC/MS/MS) detected diphenhydramine in blood and urine. Further quantification revealed the postmortem concentrations to be 0.44 µg/mL in blood and 2500 µg/mL in urine. CONCLUSIONS: The cause of death was determined to be hypothermia. Diphenhydramine-induced drowsiness and possible intrinsic cardiac factor may have led to prolonged impaired consciousness, preventing his ability to escape from the running cold water leading to hypothermia and death.

Abnormal Microscopic Findings in the Placenta Correlate With the Severity of Fetal Heart Failure.

BACKGROUND: This study investigated the association between placental pathology and fetal heart failure.Methods and Results: Singletons with a congenital heart defect (CHD) and/or arrhythmia (n=168) and gestational age-matched controls (n=52) were included in the study. The associations between macro- and microscopic abnormal findings of the placenta and the severity of fetal heart failure were evaluated using the cardiovascular profile (CVP) score. Nine features were microscopically identified and assessed in sections of the placenta: premature villi, edematous villi, fibrotic villi, chorioamnionitis, chorangiosis, fibrin deposition, subchorionic hematoma, infarcted villi, and nucleated red blood cells in villous vessels. Among singletons with CHD and/or arrhythmia, the final CVP score was ≥8 in 140 cases, 6 or 7 in 15 cases, and ≤5 in 13 cases. Microscopic analysis showed that the frequency and severity of premature and edematous villi and increased nucleated red blood cells in villous vessels were greater in cases of fetal heart failure. These microscopic findings were more common and severe in cases with a final CVP score ≤5 than in gestational age-matched controls. The prevalence of abnormal macroscopic findings of the placenta and umbilical cord was similar regardless of the severity of fetal heart failure. CONCLUSIONS: Premature and edematous villi and increased nucleated red blood cells in villous vessels were correlated with the severity of fetal heart failure in cases of CHD and/or arrhythmia.

Local Variation and Age-Related Change in Atrial and Ventricular Myocardial Contiguity at the Atrioventricular Junction in Human Hearts.

Background: We explored the histologic patterns of and age-related changes in atrial and ventricular myocardial contiguity at the left and right atrioventricular (AV) junction that could be a target site for catheter ablation. Methods and Results: Twenty-three structurally normal adult hearts obtained at autopsy were studied. The 2 AV annuli were divided into 13 clinically recognized portions in which we measured distance between the atrial and ventricular myocardium at the AV junction. Overall, measured distance was less on the right than left side (mean [±SD] 0.74±0.59 vs. 1.15±0.78 mm, respectively), and distance increased gradually with age. The gap was smallest at the anterolateral portion on the right side and posterolateral portion on the left side. Three specific features were noted, namely extension of the ventricular myocardium (coarse trabeculae) towards the atrium on the right side of the AV junction, extension of the atrial myocardium onto the AV valve leaflets, and a collection of small myocardial cells, perhaps including specialized cells, in the right anterolateral portion. No concealed AV muscular connections were found. Conclusions: Contiguity and separation of the myocardium at the AV junction have specific patterns, and myocardial proximity is influenced by age. These histologic features of the AV junction may prove to be informative for catheter ablation of tachyarrhythmias related to the AV junction.

High accessory pathway conductivity blocks antegrade conduction in Wolff-Parkinson-White syndrome: A simulation study.

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome is characterized by an anomalous accessory pathway (AP) that connects the atrium and ventricles, which can cause abnormal myocardial excitation and cardiac arrhythmias. The morphological and electrophysiological details of the AP remain unclear. The size and conductivity of the AP may affect conduction and WPW syndrome symptoms. METHODS: To clarify this issue, we performed computer simulations of antegrade AP conduction using a simplified wall model. We focused on the bundle size of the AP and myocardial electrical conductivity during antegrade conduction (from the atrium to the ventricle). RESULTS: We found that a thick AP and high ventricular conductivity promoted antegrade conduction, whereas a thin AP is unable to deliver the transmembrane current required for electric conduction. High ventricular conductivity amplifies transmembrane current. These findings suggest the involvement of a source-sink mechanism. Furthermore, we found that high AP conductivity blocked antegrade conduction. As AP conductivity increased, sustained outward transmembrane currents were observed. This finding suggests the involvement of an electrotonic effect. CONCLUSIONS: The findings of our theoretical simulation suggest that AP size, ventricular conductivity, and AP conductivity affect antegrade conduction through different mechanisms. Our findings provide new insights into the morphological and electrophysiological details of the AP.

Pathological findings after third- and second-generation everolimus-eluting stent implantations in coronary arteries from autopsy cases and an atherosclerotic porcine model.

Pathological changes after third-generation drug-eluting stent implantation remain unclear. We compared the tissue responses of coronary arteries after the implantation of third-generation abluminal biodegradable-polymer everolimus-eluting stent (3rd EES) and second-generation durable-polymer EES (2nd EES) using autopsy specimens and an atherosclerotic porcine model. We compared the histology of stented coronary arteries obtained by autopsy performed 1-10 months after 3rd EES (n (number of cases) = 4, stent-implanted period of 3-7 months) and 2nd EES (n (number of cases) = 9, stent-implanted period of 1-10 months) implantations. The ratio of covered stent struts was higher with 3rd EESs than with 2nd EESs (3rd; 0.824 ± 0.032 vs. 2nd; 0.736 ± 0.022, p = 0.035). Low-density lipoprotein receptor knockout minipigs were stented with 3rd or 2nd EES in the coronary arteries and the stented regions were investigated. The fibrin deposition around the 2nd EES was more prominent. Additionally, higher density of smooth muscle cells was confirmed after the 3rd EES implantation. Pathological examination after the 3rd EES demonstrated a combination of less fibrin deposition and more rapid acquisition of well-developed neointima as compared to the 2nd EES at autopsy and the atherosclerotic porcine model.

Advantages and challenges for noninvasive atrial fibrillation ablation.

PURPOSE: Although catheter ablation is an effective therapy for atrial fibrillation (AF), risks remain and improved efficacy is desired. Stereotactic radiotherapy is a well-established therapy used to noninvasively treat malignancies with precision. We sought to evaluate stereotactic arrhythmia radioablation (STAR) as a therapeutic option for treating AF. METHODS AND RESULTS: Three cancer patients with drug refractory AF were enrolled. Planning software using 3-D CT of the left atrium was used to design a desired ablation volume encompassing antral circumferential pulmonary vein isolation, roof and floor lines to create a "box" lesion set. After planning, patients were treated in the radioablation suite. STAR was able to deliver the intended radiation dose to the target in all 3 patients. No complications were observed over a follow-up period of 24 months. One patient with paroxysmal AF died from deterioration of cancer. The autopsy revealed evidence of fibroblasts and fibrogenesis in the region of atrial tissues targeted with radioablation. In one of these patients, left atrial posterior wall electrograms recorded from the esophagus before and 3 months after STAR indicated successful electrical isolation. CONCLUSIONS: This is the first report of non-invasive radioablation of the left atrium with demonstration of successful electrical isolation. Although STAR may be safe and effective in delivering ablative energy to the left atrium, further evaluation is warranted regarding effectiveness.

Fragmented QRS complex in patients with systemic lupus erythematosus at the time of diagnosis and its relationship with disease activity.

OBJECTIVE: Cardiovascular disease is an important contributor to the mortality rate of patients with systemic lupus erythematosus (SLE), which is related to SLE disease activity. Fragmented QRS (fQRS) complexes, defined by additional spikes in the QRS complex, are useful for identifying myocardial scars on electrocardiography and can be an independent predictor of cardiac events. We aimed to assess the relationship between disease activity in patients with SLE and fQRS at the time of diagnosis. METHODS: Forty-four patients with SLE were included. Patients with cardiac diseases, other rheumatic diseases, and prior treatment at the time of electrocardiography measurement were excluded. The appearance of fQRS represented exposure. The primary outcome was SLE Disease Activity Index 2000 (SLEDAI-2K). Multiple regression analysis was conducted to assess the association between fQRS and SLEDAI-2K adjusted for age, sex, and time from the estimated onset date to the date of diagnosis. RESULTS: Among patients with SLE at diagnosis, 26 (59.1%) had fQRS. The median SLEDAI-2K was 18 (interquartile range [IQR], 12-22) and 9 (IQR, 8-15) in the fQRS(+) and fQRS(-) groups, respectively. SLEDAI-2K was significantly higher in the fQRS(+) group than in the fQRS(-) group (regression coefficient, 2.69; 95% confidence interval, 0.76-4.61; p = 0.008). CONCLUSION: Our results suggested that fQRS(+) patients with SLE had high disease activity. fQRS could likely detect subclinical myocardial involvement in patients with SLE and predict long-term occurrence of cardiac events.

Chemerin-9, a potent agonist of chemerin receptor (ChemR23), prevents atherogenesis.

Plasma levels of chemerin, an adipocytokine produced from the adipose tissues and liver, are associated with metabolic syndrome and coronary artery disease (CAD). Chemerin and its analog, chemerin-9, are known to bind to their receptor, ChemR23. However, whether chemerin and chemerin-9 affect atherogenesis remains to be elucidated. We investigated the expression of chemerin and ChemR23 in human coronary arteries and cultured human vascular cells. The effects of chemerin and chemerin-9 on atheroprone phenomena were assessed in human THP1 monocytes, human umbilical vein endothelial cells (HUVECs), and human aortic smooth muscle cells (HASMCs) and aortic lesions in Apoe-/- mice. In patients with CAD, a small amount of ChemR23, but not chemerin, was expressed within atheromatous plaques in coronary arteries. Chemerin and ChemR23 were expressed at high levels in THP1 monocytes, THP1-derived macrophages, and HUVECs; however, their expression in HASMCs was weak. Chemerin and chemerin-9 significantly suppressed the tumor necrosis factor-α (TNF-α)-induced mRNA expression of adhesion and pro-inflammatory molecules in HUVECs. Chemerin and chemerin-9 significantly attenuated the TNF-α-induced adhesion of THP1 monocytes to HUVECs and macrophage inflammatory phenotype. Chemerin and chemerin-9 suppressed oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cell formation associated with down-regulation of CD36 and up-regulation of ATP-binding cassette transporter A1 (ABCA1). In HASMCs, chemerin and chemerin-9 significantly suppressed migration and proliferation without inducing apoptosis. In the Apoe-/- mice, a 4-week infusion of chemerin-9 significantly decreased the areas of aortic atherosclerotic lesions by reducing intraplaque macrophage and SMC contents. Our results indicate that chemerin-9 prevents atherosclerosis. Therefore, the development of chemerin analogs/ChemR23 agonists may serve as a novel therapeutic target for atherosclerotic diseases.

Occurrence of a primary liver cancer with an unusual histologic appearance as a late Fontan complication.

The Fontan procedure is an open heart procedure performed in pediatric patients with a particular congenital cardiac anomaly known as a univentricular heart. The procedure is used to reroute the systemic venous blood from the inferior vena cava directly to the pulmonary artery. It improves patients' prognoses, but various late-phase extracardiac complications that manifest when patients reach adolescence have been recognized. These complications, pulmonary arteriovenous fistula and protein losing gastroenteropathy, for example, present significant challenges in the management of adults with Fontan circulation. Liver fibrosis is another possible late-phase complication and one of the most serious. Development of a neoplasm, usually a hepatocellular carcinoma, is sometimes reported. We encountered a young patient in whom Fontan circulation led to the development of a histologically unusual liver cancer that resembled the poorly differentiated hepatocellular carcinoma or the combined hepatocellular-cholangiocarcinoma with stem-cell features described in the latest WHO classification.

Lymph Vessel Proliferation on Cardiac Biopsy May Help in the Diagnosis of Cardiac Sarcoidosis.

Background The diagnosis of cardiac sarcoidosis ( CS ) is challenging because endomyocardial biopsy has only a 20% to 30% sensitivity rate for diagnosis and it presents with similar clinical features of idiopathic dilated cardiomyopathy ( DCM ). Lymphatic vessel proliferation in pulmonary sarcoidosis has been previously demonstrated. In this study, we compared endomyocardial biopsy samples obtained from patients with CS and DCM to determine whether lymph vessel counts using D2-40 immunostaining can be utilized as a complementary tool to distinguish CS from DCM . Methods and Results Endomyocardial biopsy tissues were obtained from 62 patients with CS (30 patients with a diagnosis made histologically, 32 patients with a diagnosis made clinically), and hematoxylin/eosin, Masson trichrome, and D2-40 immunostaining were performed. Their results were compared with those from 53 patients with DCM. The histological CS group showed significantly increased lymphatic vessels (12.0 [4.0-40.0] versus 2.6 [1.9-3.4], P<0.0001) and more severe mosaic fibrosis ( P<0.0001) compared with the DCM group. The optimal threshold was 7.5 lymphatic vessels, and this resulted in a sensitivity of 0.67 and specificity of 0.96. The clinical CS group diagnosed according to Japanese Circulation Society 2016 criteria showed increased lymphatic vessels (4.0 [3.3-9.0] versus 2.6 [1.9-3.4], P<0.0001), more severe mosaic fibrosis ( P<0.0001), more inflammatory cell infiltration (53% versus 0%, P<0.0001), and fatty infiltration within fibroblasts (50% versus 17%, P=0.0012) compared with the DCM group. The optimal threshold of lymphatic vessels was 3.5, which resulted in a sensitivity of 0.75 and specificity of 0.68. Conclusions Lymphatic vessel counts using D2-40 immunostaining may help to distinguish clinical CS without granuloma from DCM .

Successful use of last-option infrapopliteal rotational atherectomy despite microembolisation: Peripheral rotational atherectomy and microembolisation.

Calcified lesions pose a technical challenge even in contemporary endovascular intervention. A 71-year-old man who had been receiving haemodialysis required infrapopliteal revascularisation for the treatment of ischaemic infectious gangrene of the right toes. Baseline angiography suggested that the multiple stenotic lesions in the anterior tibial artery were amenable to endovascular therapy for the purpose of establishing one straight-line flow to the foot. However, even a 1.25×15 mm semi-compliant balloon catheter failed to cross and dilate the focal lesion because of the underlying severe calcification in the mid segment of the anterior tibial artery. We adjunctively used high-speed rotational atherectomy with the ROTABLATOR device (1.5 mm burr) to ablate the focal calcified lesion while paying attention to minimise the ablation length and the ablation time. Subsequent balloon angioplasty with a 2.0×40 mm balloon catheter was successful. The skin perfusion pressure in the right foot increased from 32 to 48 mmHg, suggesting a high probability of wound healing. Pathological examination of the right toe amputated on schedule found non-clinically relevant microembolisation involving a couple of cholesterol crystals (20-30 µm) located in the arterioles and capillaries of the necrotic tissue. As an adjunctive device, the ROTABLATOR could provide a last resort for limb salvage, albeit that microembolisation can occur.

Three-dimensional histologic reconstruction of remnant functional accessory atrioventricular myocardial connections in a case of Wolff-Parkinson-White syndrome.

Myocardial bundles working as accessory pathways in Wolff-Parkinson-White (WPW) syndrome are generally tiny tissues, so elucidating the culprit histology of atrioventricular (AV) myocardial connections requires careful serial sectioning of the AV junction. We performed a postmortem examination of accessory AV myocardial connections in an 84-year-old man who died from pneumonia 20 years after surgical cryoablation for WPW syndrome. Three-dimensional reconstruction images of serial histologic sections revealed accessory AV connections between the atrial and ventricular myocardium in the vicinity of the cryoablation scar. The remnant myocardial bridge was 4 mm wide and made up of multiple discontinuous fibers. This case was informative in that it provided for visualization of the histologic morphology of a remnant bundle of Kent.

Pathology after a combination of sequential and simultaneous unipolar radiofrequency ablation of ventricular tachycardia in a postmortem heart with cardiac sarcoidosis.

This report shows a postmortem examination of a heart performed in a patient with cardiac sarcoidosis undergoing a sequential and simultaneous unipolar radiofrequency ablation. A combination of a sequential and simultaneous unipolar radiofrequency ablation might be useful for creating transmural ablation lesions on the interventricular septum in patients with cardiac sarcoidosis.

Anti-Atherogenic Effects of Vaspin on Human Aortic Smooth Muscle Cell/Macrophage Responses and Hyperlipidemic Mouse Plaque Phenotype.

Vaspin (visceral adipose tissue-derived serine protease inhibitor) was recently identified as a novel adipocytokine with insulin-sensitizing effects. Serum vaspin levels are reported either increased or decreased in patients with coronary artery disease. Our translational research was performed to evaluate the expression of vaspin in human coronary atherosclerotic lesions, and its effects on atherogenic responses in human macrophages and human aortic smooth muscle cells (HASMC), as well as aortic atherosclerotic lesion development in spontaneously hyperlipidemic Apoe−/− mice, an animal model of atherosclerosis. Vaspin was expressed at high levels in macrophages/vascular smooth muscle cells (VSMCs) within human coronary atheromatous plaques. Vaspin significantly suppressed inflammatory phenotypes with nuclear factor κB down-regulation in human macrophages. Vaspin significantly suppressed oxidized low-density lipoprotein-induced foam cell formation with CD36 and acyl-coenzyme A: cholesterol acyltransferase-1 down-regulation and ATP-binding cassette transporters A1 and G1, and scavenger receptor class B type 1 up-regulation in human macrophages. Vaspin significantly suppressed angiotensin II-induced migration and proliferation with ERK1/2 and JNK down-regulation, and increased collagen production with phosphoinositide 3-kinase and Akt up-regulation in HASMCs. Chronic infusion of vaspin into Apoe−/− mice significantly suppressed the development of aortic atherosclerotic lesions, with significant reductions of intraplaque inflammation and the macrophage/VSMC ratio, a marker of plaque instability. Our study indicates that vaspin prevents atherosclerotic plaque formation and instability, and may serve as a novel therapeutic target in atherosclerotic cardiovascular diseases.

Neopterin Counters Vascular Inflammation and Atherosclerosis.

BACKGROUND: Neopterin, a metabolite of GTP, is produced by activated macrophages and is abundantly expressed within atherosclerotic lesions in human aorta and carotid and coronary arteries. We aimed to clarify the influence of neopterin on both vascular inflammation and atherosclerosis, as neither effect had been fully assessed. METHODS AND RESULTS: We investigated neopterin expression in coronary artery lesions and plasma from patients with coronary artery disease. We assessed the atheroprotective effects of neopterin in vitro using human aortic endothelial cells, human monocyte-derived macrophages, and human aortic smooth muscle cells. In vivo experiments included a study of aortic lesions in apolipoprotein E-deficient mice. Neopterin expression in coronary artery lesions and plasma was markedly increased in patients with versus without coronary artery disease. In human aortic endothelial cells, neopterin reduced proliferation and TNF-α (tumor necrosis factor α)-induced upregulation of MCP-1 (monocyte chemotactic protein 1), ICAM-1 (intercellular adhesion molecule 1), and VCAM-1 (vascular cell adhesion molecule 1). Neopterin attenuated TNF-α-induced monocyte adhesion to human aortic endothelial cells and the inflammatory macrophage phenotype via NF-κB (nuclear factor-κB) downregulation. Neopterin suppressed oxidized low-density lipoprotein-induced foam cell formation associated with CD36 downregulation and upregulation of ATP-binding cassette transporters A1 and G1 in human monocyte-derived macrophages. In human aortic smooth muscle cells, neopterin suppressed angiotensin II-induced migration and proliferation via c-Src/Raf-1/ERK1/2 downregulation without inducing apoptosis. Exogenous neopterin administration and endogenous neopterin attenuation with its neutralizing antibody for 4 weeks retarded and promoted, respectively, the development of aortic atherosclerotic lesions in apolipoprotein E-deficient mice. CONCLUSIONS: Our results indicate that neopterin prevents both vascular inflammation and atherosclerosis and may be induced to counteract the progression of atherosclerotic lesions. Consequently, neopterin could be of use as a novel therapeutic target for atherosclerotic cardiovascular diseases.

Catestatin Prevents Macrophage-Driven Atherosclerosis but Not Arterial Injury-Induced Neointimal Hyperplasia.

Catestatin, a catecholamine-release inhibitory peptide, has multiple cardiovascular activities. Conflicting results have been recently reported by increased or decreased plasma levels of catestatin in patients with coronary artery disease (CAD). However, there have been no previous reports regarding the effects of catestatin on arteriosclerosis. This study evaluated the vasoprotective effects of catestatin on human macrophages, human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs) in vitro, and aortic atherosclerosis and wire injury-induced femoral artery neointimal hyperplasia in apolipoprotein E-deficient (ApoE-/-) mice fed with a high-cholesterol diet. Histological expression of catestatin in coronary artery lesions and its plasma level were compared between CAD and non-CAD patients. Catestatin was abundantly expressed in cultured human monocytes, macrophages, HASMCs and HUVECs. Catestatin significantly suppressed lipopolysaccharide-induced upregulation of tumour necrosis factor-α, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in HUVECs. Catestatin significantly suppressed inflammatory responses and oxidized low-density lipoprotein-induced foam cell formation associated with acyl-CoA:cholesterol acyltransferase-1 downregulation and ATP-binding cassette transporter A1 upregulation in human macrophages. Catestatin significantly suppressed migration, proliferation and collagen-1 expression without inducing apoptosis, and increased elastin and fibronectin expression in HASMCs. Administration of catestatin into ApoE-/- mice significantly retarded entire aortic atherosclerotic lesions with declined contents of macrophages, SMCs and collagen fibres in atheromatous plaques, but not the femoral artery injury-induced neointimal hyperplasia. In CAD patients, catestatin levels were significantly decreased in plasma but increased in coronary atheromatous plaques. This study provided the first evidence that catestatin could prevent macrophage-driven atherosclerosis, but not SMC-derived neointimal hyperplasia after vascular injury.