Integrated multi-omic characterization of congenital heart disease.

The heart, the first organ to develop in the embryo, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of patients with CHD survive into adulthood, but many suffer premature death from heart failure and non-cardiac causes1. Here, to gain insight into this disease progression, we performed single-nucleus RNA sequencing on 157,273 nuclei from control hearts and hearts from patients with CHD, including those with hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot, two common forms of cyanotic CHD lesions, as well as dilated and hypertrophic cardiomyopathies. We observed CHD-specific cell states in cardiomyocytes, which showed evidence of insulin resistance and increased expression of genes associated with FOXO signalling and CRIM1. Cardiac fibroblasts in HLHS were enriched in a low-Hippo and high-YAP cell state characteristic of activated cardiac fibroblasts. Imaging mass cytometry uncovered a spatially resolved perivascular microenvironment consistent with an immunodeficient state in CHD. Peripheral immune cell profiling suggested deficient monocytic immunity in CHD, in agreement with the predilection in CHD to infection and cancer2. Our comprehensive phenotyping of CHD provides a roadmap towards future personalized treatments for CHD.

Identification and verification of promising diagnostic biomarkers in patients with hypertrophic cardiomyopathy associate with immune cell infiltration characteristics.

AIMS: To explore immune cell infiltration characteristics of, and hub genes associated with, hypertrophic cardiomyopathy (HCM). MATERIALS AND METHODS: The GSE130036 dataset was downloaded and the differentially expressed genes (DEGs) were identified. The DEGs were analyzed via the CIBERSORT algorithm to understand the composition of 22 immune cell types between the HCM and normal myocardial tissue specimens. Weighted gene co-expression network analysis (WGCNA) was performed to segregate the DEGs into several modules and explore correlation between the key modules and specific immune cells enriched in the myocardial tissues of HCM patients. The biofunctional and disease enrichment of the genes among the modules was explored, and hub genes serving as potential biomarkers of HCM were identified. These genes were validated by GSE36961 dataset, and the discrimination ability was assessed by receiver operating characteristic curve analysis. KEY FINDINGS: CIBERSORT analysis showed that neutrophils and B-cells (naive and memory B-cells) were highly abundant in HCM samples, while macrophages (M0, M1, M2) were highly abundant in normal samples. WGCNA analysis of the DEGs yielded seven modules, and the gray and yellow modules were strongly associated with neutrophils and B-cells, and with macrophages, respectively. Yellow module genes were mainly functional in immune and inflammation processes. Gray module genes were mainly functional in the transportation of intercellular substances. SLITRK4 and CD163 showed a notably high area under the curve values in both datasets and may serve as potential biomarkers for HCM. SIGNIFICANCE: SLITRK4 and CD163 may be promising Diagnostic Biomarkers of Hypertrophic Cardiomyopathy.

Relation between neutrophil-to-lymphocyte ratio and mortality in patients with hypertrophic cardiomyopathy.

Aim: We assessed the prognostic value of neutrophil-to-lymphocyte ratio (NLR) for all-cause mortality in patients with hypertrophic cardiomyopathy (HCM). Methods & results: A total of 354 HCM patients were enrolled. There were 44 all-cause mortality in total. Patients in the third tertile of NLR had the highest all-cause mortality rate of 5.2 per 100 person-years. Patients in tertile 3 had a significantly higher risk of all-cause mortality with adjusted hazard ratio of 2.4 (95% CI: 1.0-5.4; p = 0.040) when compared with that of patients in tertile 1. No significant interactions between NLR and other variables were observed during subgroup analysis. Conclusion: NLR was an independent risk factor for all-cause mortality in HCM patients.

Monocyte to high-density lipoprotein cholesterol ratio predicts adverse cardiac events in patients with hypertrophic cardiomyopathy.

Aim: The aim of the study was to investigate the monocyte count to HDL cholesterol ratio (MHR) on the prognosis of patients with hypertrophic cardiomyopathy (HCM). Materials & methods: A total of 411 patients with HCM were assessed. The primary end point was cardiovascular death or malignant arrhythmic events. Results: During the follow-up, primary end point was developed in 54 (13.1%) patients. Receiver operating characteristic (ROC) analysis showed that using a cut-off level of 14.57, MHR predicted the occurrence of primary end point with a sensitivity of 72% and specificity of 72%. In the multivariate model, high MHR was the only significant predictor of the primary end point. Conclusion: This study showed that higher MHR level is an independent predictor of malignant arrhythmia and death in patients with HCM.

Anti-calreticulin antibodies and calreticulin in sera of patients diagnosed with dilated or hypertrophic cardiomyopathy.

Distinct cellular level of the Ca2+-binding chaperone calreticulin (CRT) is essential for correct embryonal cardiac development and postnatal function. However, CRT is also a potential autoantigen eliciting formation of antibodies (Ab), whose role is not yet clarified. Immunization with CRT leads to cardiac injury, while overexpression of CRT in cardiomyocytes induces dilated cardiomyopathy (DCM) in animals. Hence, we analysed levels of anti-CRT Ab and calreticulin in the sera of patients with idiopatic DCM and hypertrophic cardiomyopathy (HCM). ELISA and immunoblot using human recombinant CRT and Pepscan with synthetic, overlapping decapeptides of CRT were used to detect anti-CRT Ab. Serum CRT concentration was tested by ELISA. Significantly increased levels of anti-CRT Ab of isotypes IgA (p < 0.001) and IgG (p < 0.05) were found in patients with both DCM (12/34 seropositive for IgA, 7/34 for IgG) and HCM (13/38 seropositive for IgA, 11/38 for IgG) against healthy controls (2/79 for IgA, 1/79 for IgG). Titration analysis in seropositive DCM and HCM patients documented anti-CRT Ab detected at 1/1600 dilution for IgG and 1/800 for IgA (and IgA1) and at least at 1/200 dilution for IgA2, IgG1, IgG2 and IgG3. Pepscan identified immunogenic CRT epitopes recognized by IgA and IgG Ab of these patients. Significantly increased levels of CRT relative to healthy controls were found in sera of patients with HCM (p < 0.01, 5/19). These data extend the knowledge of seroprevalence of anti-CRT Ab and CRT, and suggest possible involvement of autoimmune mechanisms directed to CRT in some forms of cardiomyopathies, which are clinically heterogeneous.

Hypertrophic cardiomyopathy secondary to hepatitis C virus-related vasculitis.

: Almost invariably associated with chronic HCV infection, cryoglobulinemic vasculitis is a small-vessel vasculitis commonly affecting the skin, kidneys, and peripheral nervous system. Cardiac involvement, possibly due to cardiac microcirculation involvement, is an utterly rare and severe complication. We describe a case of hypertrophic cardiomyopathy secondary to cryoglobulinemic vasculitis. Evaluation with transthoracic cardiac ultrasound and cardiac MRI evidenced severe left ventricular hypertrophy and diffuse hypokinesia, a marked decrease in left ventricular ejection fraction, and a subtle late enhancement of inferior and lateral left ventricular walls. Upon clinical stabilization, the patient received treatment with anti-CD20 monoclonal antibody rituximab. Clinical and radiological follow-up with cardiac ultrasound and cardiac MRI documented a dramatic and sustained clinical improvement, with marked reduction of left ventricular hypertrophy, resolution of late enhancement, recovery of left ventricular contractility and function.

Diabetes, oxidative stress, molecular mechanism, and cardiovascular disease--an overview.

In recent years, diabetes and its associated complications have come to represent a major public health concern. It is a complex disease characterized by multiple metabolic derangements and is known to impair cardiac function by disrupting the balance between pro-oxidants and antioxidants at the cellular level. The subsequent generation of reactive oxygen species (ROS) and accompanying oxidative stress are hallmarks of the molecular mechanisms responsible for cardiovascular disease. Among several oxidative stress-mediated mechanisms that have been proposed, ROS-mediated oxidative stress has received the most attention. ROS have been shown to interact with proteins, lipids, and DNA, causing damage to the cellular macromolecules and subsequently, deterioration of cellular function. Induction of thioredoxin-1 (Trx1) gene expression has been demonstrated to protect the diabetic myocardium from dysfunction by reducing oxidative stress and enhancing the expression of heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF). The failure of antioxidants to consistently demonstrate clinical benefit necessitates further investigation of the role of oxidative stress in diabetes-mediated cardiovascular disease.

Heart changes in 17-day-old fetuses of diabetic ICR (Institute of Cancer Research) mothers: improvement with maternal immune stimulation.

Maternal diabetes mellitus is associated with increased fetal teratogenesis, including cardiovascular defects. Non-specific maternal immune stimulation with Freund's complete adjuvant (FCA) or interferon gamma (IFNgamma) has been associated with protection against birth malformations. Using a diabetic mouse model, late-gestation fetal heart and great vessel morphology were analyzed. Four groups of mice were used: non-diabetic females as a control group, hyperglycemic females induced by streptozotocin as a diabetic group, and diabetic females injected either with FCA or IFNgamma. At day 17 of gestation, females were euthanized and one fetus was arbitrarily selected per litter for fixation and sectioning. Treatment-induced changes in cardiac development were assessed from digital images of serial sections taken at standardized levels in the thorax. One-way parametric and non-parametric ANOVA and ordinal logistic regression were performed to compare the difference among groups (P<0.05). Maternal hyperglycemia altered morphology of the late-gestation fetal mouse heart by causing ventricular chamber dilation, sectional myocardial reduction, and an increase in transversal aortic area. FCA protected the fetal heart from cavitary dilation in diabetic mothers. FCA and IFNgamma protected the fetal heart against reduction of myocardial area, and ascending thoracic aorta dilation. Consequences of late gestation heart chamber dilation and myocardial reduction are not yet known. Maternal immune stimulation partially protected against these developmental defects by mechanisms that remain unclear.

HLA-DPbeta chain may confer the susceptibility to hepatitis C virus-associated hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a heart muscle disease characterized by hypertrophy and diastolic dysfunction of cardiac ventricles. It is suggested that one possible aetiology of HCM is the hepatitis C virus (HCV) infection, but molecular mechanisms underlying development of HCV-associated HCM (HCV-HCM) remains unknown. Because the human leucocyte antigen (HLA) molecule is involved in the control of progression/suppression of viral infection, extensive HLA allelic diversity may modulate the post-infectious course of HCV and pathogenesis of HCV-HCM. Here we undertook a case-control study with 38 patients with HCV-HCM and 132 unrelated healthy controls to reveal the potential impact of polymorphisms in seven classical and two non-classical HLA genes on the pathogenesis of HCV-HCM. It was found that DPB1*0401 and DPB1*0901 were significantly associated with increased risk to HCV-HCM in dominant model (P < 0.028, OR = 3.94, 95% confidence interval (CI) = 1.19, 13.02) and in recessive model (P < 0.007, OR = 9.85, 95% CI = 1.83, 53.04), respectively. The disparity in the gene-dose effect by two susceptible DPB1 alleles may be attributable to the difference between the susceptible (36 A and 55 A) and resistant (8L, 9F, 11G, 57E and 76M) residue-combination consisting of DPbeta anchor pocket for antigenic peptide-binding. These results implied that the HLA-DP molecules with specificity pocket appropriate for HCV antigen(s) might confer the progressive process of HCM among the HCV-infected individuals.

[Significance of immunological investigations in the studying of various forms of cardiomyopathy].

The data concerning the role of the immune and inflammatory reactions activation in formation of dilatational and hypertrophic cardiomyopathy were presented. The dependence of the humoral-inflammatory disbalance progressing on the processes of the apoptosis and inflammatory cytokins level regulation, determining the immune answer disorder degree in relation with cardiomyopathy form, was established.

Antigen-specific effects of autoantibodies against sarcolemmal Na-K-ATPase pump in immunized cardiomyopathic rabbits.

OBJECTIVES: We examine antigen-specific actions of autoantibodies directed against sarcolemmal Na-K-ATPase. BACKGROUND: Autoantibodies against some receptors or pumps were detected in patients with dilated cardiomyopathy. Although immunoglobulin adsorption therapy improved cardiac function in such patients, direct pathogenic effects of autoantibodies remain to be proven. METHODS: Japanese white rabbits were immunized once a month with purified Na-K-ATPase (NKA rabbits, n=10) or a synthetic peptide corresponding to the second extracellular loop of beta1-adrenergic receptors (beta rabbits, n=10), respectively. Control rabbits (n=10) received vehicle in the same manner. RESULTS: At 6 months, cardiac hypertrophy along with increased left ventricular end-diastolic pressure was observed in both NKA and beta rabbits, and inhibitory G protein level increased in both NKA and beta rabbits. Histological findings showed similar myocyte hypertrophy and interstitial fibrosis in both rabbits. Enzymatic activities of Na-K-ATPase were lower in NKA rabbits than in other groups. Immunoblotting showed that alpha3-isoform of Na-K-ATPase was selectively reduced in myocardium from NKA rabbits. CONCLUSIONS: Our present findings suggested that isoform-specific alterations of myocardial Na-K-ATPase activity were induced by immunizing rabbits. This was not secondary change due to cardiac hypertrophy. Thus, autoantibodies against sarcolemmal Na-K-ATPase have antigen-specific effect on the heart in vivo.

N-terminal atrial natriuretic peptide immunoreactivity in plasma of cats with hypertrophic cardiomyopathy.

Atrial natriuretic peptide (ANP) is an important regulator of fluid homeostasis and vascular tone. We sought to compare N-terminal ANP immunoreactivity (ANP-IR) in plasma from cats with and without hypertrophic cardiomyopathy (HCM). Secondarily, we evaluated relationships between ANP-IR and echocardiographical variables in cats with HCM and healthy cats. Venous blood samples were obtained from 17 cats with HCM and from 19 healthy cats. Plasma ANP-IR concentration was determined by an enzyme-linked immunoassay. Two cats with HCM had clinical evidence of congestive heart failure; the remainder had subclinical disease. Plasma ANP-IR concentration was higher in cats with HCM (3,808 +/- 1,406 fmol/L, mean +/- SD) than in control cats (3,079 +/- 1,233 fmol/L), but this difference was not statistically significant (P = .11; 95% confidence interval [CI] = -166 to 1,622). There was a significant, but modest correlation between plasma ANP-IR concentration and left ventricular posterior wall thickness (r = 0.42; P = .01). Additionally, plasma ANP-IR concentration was weakly correlated with left atrial size (r = 0.35; P = .03). A linear regression model was developed to further explore these relationships. Atrial size and wall thickness were included in the model; the 2 explanatory variables had an interactive effect on plasma ANP-IR concentration (R2 = 0.27; P = .02). There was no appreciable correlation between plasma ANP-IR concentration and any other echocardiographical variable. In a population that included cats with subclinical disease, those with HCM did not have significantly higher plasma ANP-IR concentration than did healthy cats. An exploratory multivariable regression analysis suggested a linear relationship between ANP-IR concentration and atrial size, wall thickness, and their interaction.

The haplotype block, NFKBIL1-ATP6V1G2-BAT1-MICB-MICA, within the class III-class I boundary region of the human major histocompatibility complex may control susceptibility to hepatitis C virus-associated dilated cardiomyopathy.

Cardiomyopathy is a heart muscle disease with impaired stretch response that can result in severe heart failure and sudden death. A small proportion of hepatitis C virus (HCV)-infected patients may be predisposed to develop dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). The molecular mechanisms involved in the predisposition remain unknown due in part to the lack of information on their genetic background. Because the human leukocyte antigen (HLA) region has a pivotal role in controlling the susceptibility to HCV-induced liver disease, we hypothesized that particular HLA alleles and/or non-HLA gene alleles within the human major histocompatibility complex (MHC) genomic region might control the predisposition to HCV-associated DCM (HCV-DCM) and/or HCV-associated HCM (HCV-HCM). Here, we present mapping results of the MHC-related susceptibility gene locus for HCV-associated cardiomyopathy by analyzing microsatellite and single nucleotide polymorphism markers. To delineate the susceptibility locus, we genotyped 44 polymorphic markers scattered across the entire MHC region in a total of 59 patients (21 HCV-DCM and 38 HCV-HCM) and 120 controls. We mapped HCV-DCM susceptibility to a non-HLA gene locus spanning from NFKBIL1 to MICA gene loci within the MHC class III-class I boundary region. Our results showed that HCV-DCM was more strongly associated with alleles of the non-HLA genes rather than the HLA genes themselves. In addition, no significant association was found between the MHC markers and HCV-HCM. This marked difference in the MHC-related disease susceptibility for HCV- associated cardiomyopathy strongly suggests that the development of HCV- DCM and HCV-HCM is under the control of different pathogenic mechanisms.

Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction.

BACKGROUND: Inflammatory mechanisms have been proposed to be important in heart failure (HF), and cytokines have been implicated to add to the progression of HF. However, it is unclear whether such mechanisms are already activated when hypertrophied hearts still appear well-compensated and whether such early mechanisms contribute to the development of HF. METHODS AND RESULTS: In a comprehensive microarray study, galectin-3 emerged as the most robustly overexpressed gene in failing versus functionally compensated hearts from homozygous transgenic TGRmRen2-27 (Ren-2) rats. Myocardial biopsies obtained at an early stage of hypertrophy before apparent HF showed that expression of galectin-3 was increased specifically in the rats that later rapidly developed HF. Galectin-3 colocalized with activated myocardial macrophages. We found galectin-3-binding sites in rat cardiac fibroblasts and the extracellular matrix. Recombinant galectin-3 induced cardiac fibroblast proliferation, collagen production, and cyclin D1 expression. A 4-week continuous infusion of low-dose galectin-3 into the pericardial sac of healthy Sprague-Dawley rats led to left ventricular dysfunction, with a 3-fold differential increase of collagen I over collagen III. Myocardial galectin-3 expression was increased in aortic stenosis patients with depressed ejection fraction. CONCLUSIONS: This study shows that an early increase in galectin-3 expression identifies failure-prone hypertrophied hearts. Galectin-3, a macrophage-derived mediator, induces cardiac fibroblast proliferation, collagen deposition, and ventricular dysfunction. This implies that HF therapy aimed at inflammatory responses may need to be targeted at the early stages of HF and probably needs to antagonize multiple inflammatory mediators, including galectin-3.

Role for interleukin-1 beta in Trypanosoma cruzi-induced cardiomyocyte hypertrophy.

Chagas' disease, the leading cause of heart failure in Latin America, results from infection with the intracellular protozoan parasite Trypanosoma cruzi. Host cell responses elicited in the myocardium early in the infective process are thought to be critical for establishment of infection by this pathogen; however, these changes have not been well characterized. We report here that primary cardiomyocytes undergo hypertrophy as an early response to T. cruzi infection. The T. cruzi-elicited hypertrophic response is characterized by increased expression of genes encoding the contractile proteins MyHC beta and MyHC alpha, followed by an approximately twofold increase in cell size. Hypertrophy was observed in both parasite-containing and noninfected cell populations represented in T. cruzi-infected cultures, indicating the involvement of a soluble mediator in this process. Conditioned medium harvested from T. cruzi-infected cultures, which contained significant levels of interleukin-1 beta (IL-1 beta) but not endothelin-1 or tumor necrosis factor alpha, was sufficient to induce hypertrophy in isolated cardiomyocytes. Addition of a high-affinity receptor chimera, IL-1 trap, to cardiomyocyte cultures blocked the overall increase in cell size elicited by T. cruzi. These novel findings indicate that IL-1 beta, which is rapidly induced in response to T. cruzi, promotes cardiomyocyte hypertrophy early in the infective process and may contribute to maintenance of cardiomyocyte function during establishment of T. cruzi infection in the heart.

Cardiomyopathy: molecular and immunological aspects (review).

Idiopathic cardiomyopathy is reviewed from molecular standpoint. About a half of all patients with hypertrophic cardiomyopathy show intra-familial occurrence. In familial hypertrophic cardiomyopathy, nine gene abnormalities have been discovered in the sarcomere, i.e. the genes of beta cardiac myosin heavy chain, cardiac troponin T, alpha-tropomyosin, cardiac myosin binding protein-C, essential or regulatory myosin light chain, cardac troponin I, alpha-cardiac actin, and titin. Sudden death can occur in patients with familial-type hypertrophic cardiomyopathy with abnormalities of the cardiac troponin T or troponin I gene, even if hypertrophy is not marked. Some cases of familial dilated cardiomyopathy show gene abnormalities for cytoskeletal components such as desmin and laminin A/C. Mutations of the delta-sarcoglycan gene have also been discovered in familial or sporadic dilated cardiomyopathy. Mutations in mitochondrial genes have been observed in both hypertrophic and dilated cardiomyopathy. It is postulated that chronic viral myocarditis may sometimes lead to dilated cardiomyopathy, and hepatitis C virus is also thought to be an etiological factor. Immunological abnormalities have also been reported, such as autoantibodies against myosin, beta-receptors, ADP/ATP carrier proteins.

Antigenic stimulation in T-cell cultures in cardiomyopathies: differences in cytokine profiles.

Immune-mediated mechanisms are involved in the pathogenesis of cardiomyopathies. In this study, we investigate which pattern of immune response (Th1 or Th2) lies behind these diseases by analysing the basic cytokines secreted from PHA-cultured T lymphocytes and determining what differences, if any, exist between dilated cardiomyopathy (DMC) and hypertrophic cardiomyopathy (HCM). Two groups of patients were studied: 10 patients with DCM and 10 patients with HCM. Age- and sex-matched healthy individuals were used as controls. PHA-cultured T lymphocytes in the presence or absence of different myocardial antigen (MA) concentrations were measured. Interleukine-2 (IL-2), Interleukine-6 (IL-6) and Interferon-gamma (IFN-gamma) levels were measured in culture supernatants by an ELISA method. At the same time, delayed-type hyperactivity (DTH) against the same antigenic preparation was measured by the leukocyte migration inhibitory index technique. Patients were subdivided into DTH-positive and DTH-negative and re-examined for IL-2 cytokine expression. IL-6 levels were found to increase both in the presence and in the absence of MA in the patient groups compared to the controls. IL-2 levels were decreased in both groups, in an antigen dose-related manner. Anergic patients showed a further reduction in IL-2 levels for both groups of patients. IFN-gamma remained unaffected in the patient groups. Almost half of the patients exhibited anergy to the DTH reaction against MA. We conclude that, upon antigenic stimulation, the initially mounted immune response (increased IL-6) is somehow blocked/switched off in patients, resulting in an immunologic tolerance/unresponsiveness to MA (IL-2 decreased, IFN-gamma unchanged). Finally, increased IL-6 could lead to a perpetuation of immunologic injury through the release of oxygen-free radicals with a cytotoxic effect on the myocardium. We hypothesize an antigen-related, defective macrophage-Th1 cell reaction, which accounts for the differences in the IL-2 profile between the DCM and HCM groups, that might cause local immune responses to lead to immunosuppression (immune tolerance effect), thus contributing to the pathogenesis of cardiomyopathies.

The frequency of occurrence of anti-cardiac receptor autoantibodies and their correlation with clinical manifestation in patients with hypertrophic cardiomyopathy.

The purpose of this study was to investigate the frequency of occurrence of autoantibodies against G-protein coupled cardiovascular receptors and their relation to the clinical manifestation of hypertrophic cardiomyopathy (HCM). Autoantibodies against beta1-receptors, Muscarin-2-receptors, Angiotensin-II-receptor subtype 1 and alpha1-receptors were determined with ELISA in 52 patients with HCM (37 male, 15 female, mean age 55 +/- 15 years) and 40 healthy, age and sex matched controls. The clinical characterization of the HCM-patients included ECG, 24-h Holter, and echocardiography. The results showed that there is no significant difference in the frequency of a single autoantibody between HCM-patients and controls. However, if the number of patients who have autoantibodies against beta1-receptors and/or Muscarin-2-receptors were counted together, there are significantly more autoantibodies in HCM compared to controls (11 vs. 2, p = 0.035). Analysis of clinical data from this pooled group of patients showed that in patients with autoantibodies, heart rate variability (HRV), ultra low frequency (ULF) and very low frequency (VLF) were decreased (HRV by 20%, ULF by 50%, and VLF by 46%, p < 0.008) whereas the QTc-interval was increased by 8% (p < 0.02 each). The ratio of septal to posterior wall thickness was increased by 23% (p = 0.05), and the preejection period was prolonged by 46% in patients with autoantibodies (p < 0.001). These results suggest that the existence of these autoantibodies could be associated with an advanced stage or a severe manifestation of HCM.

CD36 deficiency has little influence on the pathophysiology of hypertrophic cardiomyopathy.

CD36 is homologous with myocardial long-chain fatty acid (LCFA) binding protein and has been suggested to relate to myocardial fatty acid metabolism. Myocardial scintigraphy with iodine-123 15-(p-iodophenyl)-3-(R, S)-methylpentadecanoic acid (BMIPP) revealed an impairment in LCFA metabolism chiefly in the hypertrophic myocardium in hypertrophic cardiomyopathy (HCM). Recently, the incidence of CD36 deficiency has been reported to be high in HCM patients, and CD36 deficiency was proposed as an etiology of hereditary HCM. However, the pathophysiological effect of CD36 deficiency on HCM has not been fully investigated. We analysed the expression of CD36 antigens on both platelets and monocytes obtained from 82 patients with HCM using two-color flow cytometry. Among the study patients, seven patients (8.5%) demonstrated type II CD36 deficiency, whereas type I CD36 deficiency was not detected. Two of 23 patients (8.7%) with a family history of HCM and five of 59 patients (8.5%) without a family history of HCM showed type II CD36 deficiency respectively. Contrary to the previous report, three of 53 patients with asymmetric septal hypertrophy (ASH) (5.7%) and four of 29 patients without ASH (13.8%) showed CD36 deficiency. Moreover, clinical characteristics, scintigraphic findings, echocardiographic data, and hemodynamic findings disclosed no significant differences between the HCM patients showing normal CD36 expression and those with CD36 deficiency. The incidence of CD36 deficiency in HCM patients is not higher than in the general population. Therefore, CD36 deficiency is not a characteristic factor of HCM and has little influence on the pathyphysiology of HCM.