<b>Objectives:</b> To summarize the characteristics of Fabry's disease with cardiac involvement. <b>Methods:</b> This was a single-center, cross-sectional, retrospective study. Patients with Fabry disease who were admitted to Zhongda Hospital Affiliated to Southeast University from January 2022 to March 2023 were included. Clinical data, laboratory results, electrocardiogram, echocardiography and cardiac magnetic resonance findings of enrolled patients were collected. Clinical presentations and imaging features of patients with Fabry's disease with cardiac involvement were summarized and analyzed. <b>Results:</b> A total of 17 patients from 8 families were included, with 9 males and diagnosis age of (44.35±13.72) years. Cardiac involvement and other organ involvement were presented in all patients and the heart was the most vulnerable organ (17/17). 24 h electrocardiogram showed frequent sinus arrhythmia in 3 patients. Echocardiography showed reduced left ventricular ejection fraction in 1 patient, myocardial hypertrophy in 13 patients, and left ventricular wall thickness ≥13 mm in 10 patients. Mitral regurgitation was observed in 11 patients and tricuspid regurgitation in 12 patients. Two patients underwent two-dimensional speckle tracking echocardiography, both revealing reduced regional longitudinal strain of the left ventricle, primarily in the basal segments. Cardiac magnetic resonance showed reduced left ventricular ejection fraction in 2 patients, myocardial hypertrophy in 16 patients, and left ventricular wall thickness≥13 mm in 14 patients. T1 value was reduced in 16 patients, with late gadolinium enhancement observed in 9 patients and "pseudo-normalization" of T1 values in 1 patient. The most susceptible target organ besides the heart was the kidneys (14/17), followed by the central nervous system (9/17). Additional findings inclucling cutaneous angiokeratoma in 4 patients, peripheral neuropathy with burning pain and hypohidrosis or hyperhidrosis in 6 patients, and corneal vortex opacities in 2 patients. <b>Conclusion:</b> The main manifestations of cardiac involvement in Fabry's disease are decreased cardiac function, left ventricular hypertrophy and myocardial fibrosis. Advanced imaging techniques such as two-dimensional speckle tracking, T1 Mapping, and late gadolinium enhancement are useful in detecting myocardial pathological changes of Fabry's disease.

To investigate the effect and related mechanism of retinoid X receptor (RXR) activation on oxidized low-density lipoprotein (ox-LDL) induced differentiation of macrophage into dendritic cell. RAW264.7 murine macrophage cell line was cultured with ox-LDL for 48 h in the absence and presence of RXR activator 9-cisRA or SR11237. Cell morphology was observed by phase contrast microscope and cell surface markers involved in dendritic cell immune maturation and activation was analyzed by FACS. Cellular reactive oxygen species production was detected by CM-H2DCFDA fluorescent probe. ox-LDL-treated RAW264.7 murine macrophage cell line differentiated into dendritic like cells after 48 h and cell surface markers CD40, CD86, CD83, MHC Class II and CD1d were upregulated. These changes could be attenuated by cotreatment with 9-cisRA or SR11237. Upregulated cell surface markers CD40, CD86, CD83, MHC Class II and CD1d by ox-LDL were decreased about 47%, 43%, 48%, 32% and 17% respectively by 9-cisRA and 38%, 38%, 46%, 36% and 32% respectively by SR11237. The effect of 9-cisRA and SR11237 was dose dependent. Cellular reactive oxygen species were significantly increased in ox-LDL-treated RAW264.7 cells (MFI 38.24 +/- 4.20 vs. 4.46 +/- 0.39, P < 0.05) and which was significantly reduced by 9-cisRA (10(-7) mol/L) and SR11237 (10(-6) mol/L) to 12.60 +/- 1.52 and 17.89 +/- 1.91 respectively (all P < 0.05). RXR activation partly inhibits the differentiation of ox-LDL induced macrophage into dendritic cell by reducing oxidative stress injury.

This study assessed cardiac function changes post embryonic stem cells (ESCs) perfusion at different concentrations in the isolated apolipoprotein-E gene deficiency (apo E-/-) and wild type (WT) hearts. apo E-/- and WT mice hearts were isolated and retrogradely perfused (Langendorff model) and ESCs were infused with different concentrations (Low dose group: 1.0 x 10(6) cells, high dose group: 2.5 x 10(6) cells). Hemodynamic parameters including coronary flow (CF), heart rate (HR), dp/dtmax, dp/dtmin, left ventricular end diastolic pressure (LVEDP), were recorded after stabilization period and at before, 5 min, 15 min and 30 min after cell perfusions. The number of cells in the transudate was counted. Cardiac function parameters were similar before cell perfusion in apo E-/- and WT hearts. Cardiac function was significantly impaired after low dose cell perfusion in apo E-/- hearts while remained unchanged in WT hearts with the exception of lowered HR. Cardiac function was also significantly impaired after high dose cell perfusion in both apo E-/- and WT hearts, especially in apo E-/- murine hearts. Most of the cells perfused into the heart were expelled after 30 min (63.2% - 77.0%). ESCs perfusion into an isolated heart, especially in the atherosclerosis-prone hearts, in the Langed off model impaired cardiac function in a concentration-dependent manner.

To observe the effect of fluid shear stress on the eNOS gene expression and NO production in endothelial progenitor cells (EPCs). The peripheral blood mononuclear cells from healthy volunteers were inducted into EPCs and divided into stationary group (0 dyn/cm(2), 1 dyn/cm(2) = 0.1 Pa), low-flow shear stress group (5 dyn/cm(2)), medium-flow shear stress group (15 dyn/cm(2)) and high-flow shear stress group (25 dyn/cm(2)). The effects of shear stress on the endothelial nitric oxide synthase (eNOS) gene expression and nitric oxide (NO) production in human EPCs were measured. Typical "spindle-shaped" appearance was shown in EPCs derived from peripheral blood mononuclear cells and were positively labeled by acetylated-LDL, lectin, FLK-1 and vWF. After 4 hours treatment with various shear stresses, the ratio of eNOS/beta-actin mRNA expression by human EPCs in low, medium and high-flow shear stress group was 0.364, 0.505 and 0.548 respectively, which was significantly higher than that in stationary group (0.183, all P < 0.05) and the NO secretion in human EPCs in low, medium and high-flow shear stress group was also significantly higher than that in stationary group (all P < 0.05). Fluid shear stress enhances the eNOS mRNA expression and NO secretion in human EPCs, therefore, shear stress could potentiate the repair efficacy of EPCs for endothelial injury.

To investigate the effects of vascular endothelial growth factor (VEGF) gene transfer with a new pseudotyped recombinant adeno-associated virus (rAAV) vector with AAV serotype 1 capsid protein (rAAV1) vector on neovascularization. PBS, rAAV1-GFP and rAAV1-VEGF vectors were added in C2C12 derived myotubes [10(5) vg (vector genomes) per cell]. Transfer efficiency was determined by fluorescent microscope and VEGF protein concentration in the culture media measured by ELISA. Ten days following ischemia in a hindlimb ischemic mouse model, PBS, 3 x 10(11)vg rAAV1-LacZ vectors and rAAV1-VEGF165 vectors were injected in ischemic thigh muscles. VEGF protein at ischemic thigh muscle was measured by ELISA at 1 month after vector infection. Capillaries and arterioles were observed by immunohistochemical analysis at 6 weeks after vector infection. GFP expression was found in 60% - 80% myotubes at 120 hours after rAAV1-GFP infection. VEGF protein peaked at the 3rd day post rAAV1-VEGF infection with an average concentration of (567.7 +/- 16.8) pg/ml. Transfer efficacy in ischemic thigh muscle was 100% one month post rAAV1-LacZ infection. The average concentration of VEGF protein in ischemic skeletal muscles is (205.4 +/- 36.1) pg/mg total protein in rAAV1-VEGF165 treated mice. Extensive angiogenesis [(147.0 +/- 13.3)/mm(2)] and arteriogenesis [(17.0 +/- 1.2)/mm(2)] were observed in ischemic skeletal muscles at 6 weeks post rAAV1-VEGF165 injection. Gene transfer with the new pseudotyped rAAV1-VEGF165 vector might be an effective therapeutic approach for ischemic cardiovascular diseases.

Hypertrophic cardiomyopathy (HCM) is a genetically and phenotypically heterogeneous disease and an Arg723Gly mutation in beta-myosin heavy chain (beta-MHC) gene was found in 3 Spanish families with malignant HCM. We detected this gene mutation in 5 Chinese pedigrees with hypertensive cardiomyopathy. Five Chinese pedigrees with HCM and 80 age-matched normal control subjects were chosen for the study. The exons in the functional regions of the beta-MHC gene were amplified with PCR and the products were sequenced, genotype and phenotype analyzed. Arg723Gly mutation was identified in exon 20 in one pedigree. In this pedigree, 13 out of 25 family members were diagnosed as HCM, 5 died of heart failure, all HCM patients in this pedigree had Arg723Gly mutation and 3 of them had NYHA III and 2 of them were diagnosed as HCM before the age of 20. Arg723Gly mutation was also one of the main disease-causing genes in Chinese familial HCM. The mutation of Arg723Gly is a malignant phenotype as shown by early progressive heart failure development and poor prognosis in this pedigree with Arg723Gly mutation.

The present study was designed to investigate whether Tumor necrosis factor (TNF)-alpha stimulates release of endothelial microparticles (EMPs) by human endothelial cells, and whether EMPs may serve as a promising marker for endothelial injury and dysfunction. Human umbilical venous endothelial cells (HUVEC) were incubated with or without TNF-alpha for 24 hours at 37 degrees C. EMPs generated on the surface of HUVEC were observed with a scanning electron microscopy. The CD31 and CD51 positive EMPs in culture supernatants were measured by flow cytometer. Fewer vesicles were observed on cell surface of control group, in TNF-alpha-stimulated one, however, cells manifested a blebby surface (eruption phenomenon) and more vesicles on surface were observed. The levels of EMPs were significantly increased in TNF-alpha stimulated cells compared with controls [CD31 + EMP, (164 +/- 63)/1000 cells vs. (42 +/- 10)/1000 cells, P < 0.05; CD51 + EMP, (260 +/- 108)/1000 cells vs. (19 +/- 4)/1000 cells, P < 0.05]. TNF-alpha can stimulate HUVEC to release EMPs which may serve as a surrogate marker for endothelial injury and dysfunction.

To investigate the relationship between endothelial progenitors cells (EPCs) and endothelium-dependent vasodilation in patients with unstable angina pectoris. Thirty patients with unstable angina pectoris (UAP) and thirty control subjects were recruited. Flow-mediated dilation (FMD) in the brachial artery was evaluated by using ultrasound Doppler flow method. The number of circulating EPCs was analyzed by flow cytometry analysis. Total mononuclear cells were isolated from peripheral blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. CD34 antigen of adherent cells was identified by immunohistochemical assay. EPCs were characterized as adherent cells double positive for FITC-UEA-I binding and DiI-acLDL uptake by direct fluorescent staining under inverted fluorescent microscope. FMD was significantly impaired in the UAP group compared with the control group (5.93% +/- 2.67% vs 11.1% +/- 4.36%, P < 0.05). There was no significant difference in NMD between two groups (13.60% +/- 5.03% vs 14.18% +/- 4.50%, P > 0.05). The number of CD34(+) cells significantly increased in the UAP group compared with the control group (0.13% +/- 0.05% vs 0.09% +/- 0.04%, P < 0.05). There was a negative association between impaired FMD and increased CD34(+) cell (r = -0.385, P < 0.05). A positive antigen of CD34 of adhesion cells and double positive adhesion cells were found. This study shows that the levels of peripheral CD34(+) cells in patients with UAP increase with an impaired endothelial function. The increase in EPCs may be an important compensatory response to acute coronary ischemia and impaired endothelium in patients with UAP.

In order to investigate the role of shear stress in the regulation of endothelial function, we assessed here effects of shear stress on tissue-type plasminogen activator in human endothelial progenitor cells (EPCs). The peripheral blood mononuclear cells were separated from healthy adult and inducted into EPCs, which were identified by double staining for the fluorescent labeled acetylated-LDL and lectin. EPCs were seeded on the small diameter artificial vessels, and then divided into four different experimental groups including stationary group, low-flow shear stress group (5 dyn/cm(2)), medium-flow shear stress group (15 dyn/cm(2)) and high-flow shear stress group (25 dyn/cm(2)). The levels of t-PA in EPC culture medium at 0 hour, 5 hours, 10 hours, 15 hours, 20 hours and 25 hours after culture were measured by enzyme-linked immunosorbent assay. The peripheral blood mononuclear cells differentiated into EPCs after induction, which were positively labeled by fluorescent acetylated-LDL and lectin. Shear stress enhanced production of the t-PA by EPCs, which was paralleled to levels and times of shear stress. Shear stress increases t-PA secretion by human EPCs, suggesting that shear stress not only regulates vascular endothelial function but also participates in the pathogenesis of arteriosclerosis.

Reduced arterial elasticity is a hallmark of aging in healthy humans independently of diseases and endothelial-cell injury and dysfunction may be responsible for this fall in arterial elasticity. We hypothesized that circulating endothelial progenitor cells (EPCs) are involved in endothelial repair and that lack of EPCs contributes to impaired arterial elasticity. A total of 56 healthy male volunteers were divided into young (n = 26) and elderly (n = 30) groups. Large and small artery elasticity indices were non-invasively assessed by using pulse wave analysis. Flow cytometer was used to count the number of circulating CD34(+) mononuclear cells (MNCs), which were isolated from peripheral blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. EPCs were characterized as adherent cells double positive staining for DiI-acLDL uptake and lectin binding with using fluorescent microscope. C(1) (large artery elasticity index) and C(2) (small artery elasticity index) were significantly reduced in the elderly group compared with those in the young group (11.73 +/- 1.45 vs 16.89 +/- 1.69 ml/mm Hg x 10, P < 0.001; 8.40 +/- 1.45 vs 10.58 +/- 1.18 ml/mm Hg x 100, P < 0.001 respectively). In parallel, the number of circulating EPCs was significantly reduced in the elderly group compared with the young group (0.13 +/- 0.02 vs 0.17 +/- 0.04%, P < 0.05). The number of circulating EPCs correlated with C(1) large and C(2) small artery elasticity indices (r = 0.47, P < 0.01; r = 0.4, P < 0.01). Fluorescent microscope was used to identify EPCs, which were double positive staining for DiI-acLDL uptake and lectin binding. The present findings suggested that the fall in circulating EPCs with subsequently impaired endothelial-cell repair and function might contribute to reduced arterial elasticity in humans with aging. The decrease in circulating EPCs could serve as a surrogate biologic measure of vascular function and human age.