Central and peripheral blood pressures in relation to the triglyceride-glucose index in a Chinese population.

BACKGROUND: The triglyceride-glucose (TyG) index has been proposed as a surrogate marker of insulin resistance. However, the relationship between the TyG index and central blood pressure (BP), has not been well studied in adults. METHODS: A total of 715 Chinese adult participants were enrolled in this study. Anthropometric and BP were assessed. The TyG index was calculated as ln[fasting triglycerides(mg/dL) × fasting glucose(mg/dL)/2]. Central BP was measured using SphygmoCor system. RESULTS: The participants were stratified into three groups based on the TyG index, and significant differences were observed in metabolic and cardiovascular parameters and the prevalence of hypertension among the groups. Both brachial (ß = 1.38, P = 0.0310; group highest vs. lowest, ß = 2.66, P = 0.0084) and aortic (ß = 2.38, P = 0.0002; group highest vs. lowest, ß = 3.96, P = 0.0001) diastolic BP were significantly and independently associated with the TyG index and increasing TyG index tertile. However, there was no independent association between the TyG index and systolic BP. A one-unit increase in the TyG index was associated with a 46% higher risk of hypertension (P = 0.0121), and compared with the lowest group, participants in the highest group had a 95% higher risk of hypertension (P = 0.0057). CONCLUSIONS: Our study demonstrates a significant and independent association between the TyG index and both brachial and aortic diastolic BP in Chinese adults. Furthermore, the TyG index was found to be an independent predictor of hypertension.

Nanocellulose/carbon nanotube/manganese dioxide composite electrodes with high mass loadings for flexible supercapacitors.

The increasing commercialization of flexible electronic products has sparked a rising interest in flexible wearable energy storage devices. Supercapacitors are positioned as one of the systems with the most potential due to their distinctive advantages: high power density, rapid charge and discharge rates, and long cycle life. However, electrode materials face challenges in providing excellent mechanical strength while ensuring sufficient energy density. This study presents a method for constructing a flexible composite electrode material with high capacitance and mechanical performance by electrochemically depositing high-quality manganese dioxide (MnO2) onto the surface of a nanocellulose (CNF) and carbon nanotube (CNT) conductive film. In this electrode material, the CNF/CNT composite film serves as a flexible conductive substrate, offering excellent mechanical properties (modulus of 3.3 GPa), conductivity (55 S/cm), and numerous active sites. Furthermore, at the interface between MnO2 and the CNF/CNT substrate, C-O-Mn bonds are formed, promoting a tight connection between the composite materials. The assembled symmetric flexible supercapacitor (FSC) demonstrates impressive performance, with an areal specific capacitance of 934 mF/cm2, an energy density of 43.10 Wh/kg, a power density of 166.67 W/kg and a long cycle life (85 % Capacitance retention after 10,000 cycles), suggesting that they hold promise for FSC applications.

A high-performance and flexible electrode film based on bacterial cellulose/polypyrrole/nitrogen-doped graphene for supercapacitors.

With the development and popularity of portable electronic devices, there is an urgent need for flexible energy storage devices suitable for mass production. We report freestanding paper electrodes for supercapacitors fabricated via a simple but efficient two-step method. Nitrogen-doped graphene (N-rGO) was first prepared via a hydrothermal method. This not only obtained nitrogen atom-doped nanoparticles but also formed reduced graphene oxide. Pyrrole (Py) was then deposited on the bacterial cellulose (BC) fibers as a polypyrrole (PPy) pseudo-capacitance conductive layer by in situ polymerization and filtered with nitrogen-doped graphene to prepare a self-standing flexible paper electrode with a controllable thickness. The synthesized BC/PPy/N15-rGO paper electrode has a remarkable mass specific capacitance of 441.9 F g-1, a long cycle life (96 % retention after 3000 cycles), and excellent rate performance. The BC/PPy/N15-rGO-based symmetric supercapacitor shows a high volumetric specific capacitance of 244 F cm-3 and a max energy density of 67.9 mWh cm-3 with a power density of 1.48 W cm-3, suggesting that they will be promising materials for flexible supercapacitors.

No significant association of serum klotho concentration with blood pressure and pulse wave velocity in a Chinese population.

Klotho, an important anti-aging protein, may be related to elevated blood pressure (BP) and arterial stiffness. We aimed to investigate associations between the serum klotho concentration and peripheral/central BP and arterial stiffness based on the carotid-femoral pulse wave velocity (cfPWV) in a Chinese population. We invited all inhabitants aged ≥ 18 years in two Dali communities for participation. The SphygmoCor system was used to record radial arterial waveforms. Aortic waveforms were derived using a generalized transfer function. The central BP was assessed by calibrating the brachial BP, which was measured using an oscillometric device. The serum klotho concentration was measured using an enzyme-linked immunosorbent assay and logarithmically transformed. Of the 716 participants (mean age: 51.9 ± 12.6 years), 467 (65.2%) were women. The median serum klotho concentration was 381.8 pg/mL. The serum klotho concentration did not significantly differ between patients with and without hypertension (P > 0.05) and between those with and without arterial stiffness (cfPWV ≥ 10 m/s) (P > 0.05). After adjusting for confounders, the serum klotho concentration was not significantly associated with the peripheral or central BP (P > 0.05) and cfPWV (P > 0.05). Our data indicated that the serum klotho concentration was not associated with BP or cfPWV in the general Chinese population.

Association of thyroid hormones with blood pressure and arterial stiffness in the general population: The Dali study.

Thyroid dysfunction plays a role in blood pressure (BP) regulation. However, the associations between thyroid function and BP and arterial stiffness in the general Chinese population without thyroid disease are unknown. This population-based cross-sectional study aimed to investigate the association between thyroid function and peripheral and central BP and arterial stiffness in Chinese individuals. After excluding those who had thyroid diseases or incomplete clinical measurements, this study included 691 participants. Of the participants, 444 (64.2%) were women and 215 (31.1%) had hypertension. After adjustment for covariates, serum FT3 was significantly associated with a higher pulse rate in both sexes. In men, each 2.72-fold increase in serum FT4 levels was associated with higher peripheral systolic BP (+10.82 mmHg, p = .005) and pulse pressure (+5.71 mmHg, p = .03). Each 2.72-fold increase in serum FT4 levels was associated with higher central systolic BP (+8.03 mmHg, p = .03) and pulse pressure (+3.89 mmHg, p = .05). In women, serum FT4 was only associated with a higher central pulse pressure (+2.96 mmHg, p = .04). After adjustment for covariates, serum FT4 was significantly associated with a faster cfPWV exclusively in men. Our study showed that serum FT4 is associated with higher peripheral and central BP and faster cfPWV in men, whereas serum FT3 is positively associated with a higher pulse rate in both sexes, indicating that the effects of thyroid function on BP and arterial stiffness are more significant in men than in women.

Full-length transcript sequencing accelerates the transcriptome research of Gymnocypris namensis, an iconic fish of the Tibetan Plateau.

Gymnocypris namensis, the only commercial fish in Namtso Lake of Tibet in China, is rated as nearly threatened species in the Red List of China's Vertebrates. As one of the highest-altitude schizothorax fish in China, G. namensis has strong adaptability to the plateau harsh environment. Although being an indigenous economic fish with high value in research, the biological characterization, genetic diversity, and plateau adaptability of G. namensis are still unclear. Here, we used Pacific Biosciences single molecular real time long read sequencing technology to generate full-length transcripts of G. namensis. Sequences clustering analysis and error correction with Illumina-produced short reads to obtain 319,044 polished isoforms. After removing redundant reads, 125,396 non-redundant isoforms were obtained. Among all transcripts, 103,286 were annotated to public databases. Natural selection has acted on 42 genes for G. namensis, which were enriched on the functions of mismatch repair and Glutathione metabolism. Total 89,736 open reading frames, 95,947 microsatellites, and 21,360 long non-coding RNAs were identified across all transcripts. This is the first study of transcriptome in G. namensis by using PacBio Iso-seq. The acquisition of full-length transcript isoforms might accelerate the transcriptome research of G. namensis and provide basis for further research.

A murine model of the exercise pressor reflex.

KEY POINTS: The decerebrate mouse provides a novel working model of the exercise pressor reflex (EPR). The decerebrate mouse model of the EPR is similar to the previously described decerebrate rat model. Studying the EPR in transgenic mouse models can define exact mechanisms of the EPR in health and disease. ABSTRACT: The exercise pressor reflex (EPR) is defined by a rise in mean arterial pressure (MAP) and heart rate (HR) in response to exercise and is necessary to match metabolic demand and prevent premature fatigue. While this reflex is readily tested in humans, mechanistic studies are largely infeasible. Here, we have developed a novel murine model of the EPR to allow for mechanistic studies in various mouse models. We observed that ventral root stimulation (VRS) in an anaesthetized mouse causes a depressor response and a reduction in HR. In contrast, the same stimulation in a decerebrate mouse causes a rise in MAP and HR which is abolished by dorsal rhizotomy or by neuromuscular blockade. Moreover, we demonstrate a reduced MAP response to VRS using TRPV1 antagonism or in Trpv1 null mice while the response to passive stretch remains intact. Additionally, we demonstrate that intra-arterial infusion of capsaicin results in a dose-related rise in MAP and HR that is significantly reduced by a selective and potent TRPV1 antagonist or is completely abolished in Trpv1 null mice. These data serve to validate the development of a decerebrate mouse model for the study of cardiovascular responses to exercise and further define the role of the TRPV1 receptor in mediating the EPR. This novel model will allow for extensive study of the EPR in unlimited transgenic and mutant mouse lines, and for an unprecedented exploration of the molecular mechanisms that control cardiovascular responses to exercise in health and disease.

Oxidative cross-linking of proteins to DNA following ischemia-reperfusion injury.

Myocardial infarction (MI) is a life-threatening condition that can occur when blood flow to the heart is interrupted due to a blockage in one or more of the coronary vessels. Current treatments of MI rapidly restore blood flow to the affected myocardium using thrombolytic agents or angioplasty. Adverse effects including inflammation, tissue necrosis, and ventricular dysfunction are, however, not uncommon following reperfusion therapy. These conditions are thought to be caused by a sudden influx of reactive oxygen species (ROS) to the affected myocardium. We employed the model of left anterior descending artery ligation/reperfusion surgery in a rat model to show that ischemia/reperfusion injury is associated with the formation of toxic DNA-protein cross-links (DPCs) in cardiomyocytes. Mass spectrometry based experiments have revealed that these conjugates were formed by a free radical mechanism and involved thymidine residues of DNA and tyrosine side chains of proteins (dT-Tyr). Quantitative proteomics experiments have identified nearly 90 proteins participating in hydroxyl radical-induced DPC formation, including ROS scavengers, contractile proteins, and regulators of apoptosis. Global proteome changes were less pronounced and included increased expression of mitochondrial proteins required for aerobic respiration and biomarkers of sarcomere breakdown following ischemia/reperfusion injury. Overall, our results are consistent with a model where sudden return of oxygen to ischemic tissues induces oxidative stress, inflammation, and the formation of DNA-protein cross-links that may contribute to reperfusion injury by desregulating gene expression and inducing cardiomyocyte death.

Chronic cyclic vagus nerve stimulation has beneficial electrophysiological effects on healthy hearts in the absence of autonomic imbalance.

Cardiovascular disease degrades the regulatory function of the autonomic nervous system. Cyclic vagus nerve stimulation (VNS) is an already FDA-approved therapy for drug-resistant epilepsy and depression, and has been shown to normalize autonomic function and improve objective measures of heart function and subjective measures of heart failure symptoms. However, it remains unclear whether VNS may induce negative effects in patients with potentially healthy hearts where VNS can be used for epileptic patients. Hence, this study aims to investigate the effects of VNS on the hearts of healthy rats with normal autonomic balance. Sprague-Dawley rats were implanted with stimulators and randomized to either Sham or VNS groups. Rats in VNS group received 10 weeks of chronic intermittent VNS via stimulation of the right cervical vagus nerve. Echocardiography was performed at Baseline (prior to VNS), Week 2, and Week 9. After 10 weeks, high-resolution optical mapping was performed in ex vivo perfused hearts to evaluate the electrophysiological remodeling that occurs in the heart as a result of the VNS therapy. Chronic VNS modified the electrophysiological properties of healthy rat hearts by reducing the action potential duration at 50% (APD50) and 80% (APD80) repolarization. Chronic VNS also affected the restitution properties of the heart at the APD50 level and increased myocardial conduction velocity (CV). VNS did not induce any significant changes to ventricular ejection fraction (EF) and spatial dispersion of APD, thus indicating that VNS did not negatively affect cardiac function. VNS also reduced the susceptibility to ventricular arrhythmias (ventricular fibrillation [VF] and ventricular tachycardia [VT]) during ex vivo programmed electrical stimulation. In summary, chronic application of cyclic VNS induces changes to the electrophysiological properties of healthy rat hearts. The observed decrease in APD and increase in CV suggest that the beneficial effects of VNS do not require the presence of existing autonomic imbalance.

Abcg2-Labeled Cells Contribute to Different Cell Populations in the Embryonic and Adult Heart.

ATP-binding cassette transporter subfamily G member 2 (Abcg2)-expressing cardiac-side population cells have been identified in the developing and adult heart, although the role they play in mammalian heart growth and regeneration remains unclear. In this study, we use genetic lineage tracing to follow the cell fate of Abcg2-expressing cells in the embryonic and adult heart. During cardiac embryogenesis, the Abcg2 lineage gives rise to multiple cardiovascular cell types, including cardiomyocytes, endothelial cells, and vascular smooth muscle cells. This capacity for Abcg2-expressing cells to contribute to cardiomyocytes decreases rapidly during the postnatal period. We further tested the role of the Abcg2 lineage following myocardial injury. One month following ischemia reperfusion injury, Abcg2-expressing cells contributed significantly to the endothelial cell lineage, however, there was no contribution to regenerated cardiomyocytes. Furthermore, consistent with previous results showing that Abcg2 plays an important cytoprotective role during oxidative stress, we show an increase in Abcg2 labeling of the vasculature, a decrease in the scar area, and a moderate improvement in cardiac function following myocardial injury. We have uncovered a difference in the capacity of Abcg2-expressing cells to generate the cardiovascular lineages during embryogenesis, postnatal growth, and cardiac regeneration.

Interfacial electron transfer of glucose oxidase on poly(glutamic acid)-modified glassy carbon electrode and glucose sensing.

The interfacial electron transfer of glucose oxidase (GOx) on a poly(glutamic acid)-modified glassy carbon electrode (PGA/GCE) was investigated. The redox peaks measured for GOx and flavin adenine dinucleotide (FAD) are similar, and the anodic peak of GOx does not increase in the presence of glucose in a mediator-free solution. These indicate that the electroactivity of GOx is not the direct electron transfer (DET) between GOx and PGA/GCE and that the observed electroactivity of GOx is ascribed to free FAD that is released from GOx. However, efficient electron transfer occurred if an appropriate mediator was placed in solution, suggesting that GOx is active. The PGA/GCE-based biosensor showed wide linear response in the range of 0.5-5.5 mM with a low detection limit of 0.12 mM and high sensitivity and selectivity for measuring glucose.

Determination of tiopronin based on the enhancement of Ru(bpy)5²âº co-reactant electrochemiluminescence.

It was found that tiopronin could strongly enhance the electrochemiluminescence of tris(2,2'-bipyridine) ruthenium(II) (Ru(bpy)3(2+)) in alkaline solution on a bare Pt electrode, based on which a sensitive, simple and rapid method for the determination of tiopronin was established. Under the optimal conditions, the logarithm of ECL enhancement has a linear relationship with the logarithm of tiopronin concentration in the range from 2.0×10(-7) to 2.0×10(-4) mol L(-1) with a detection limit of 1.0×10(-8) mol L(-1) (S/N= 3), and the relative standard deviation of 1.6% (n=7, c=5.0×10(-6) mol L(-1)). The proposed method has been applied to the determination of tiopronin in pharmaceutical preparations and the results were satisfactory with recoveries of 91.7±1.7%, 98.3±1.0% and 100.8±0.5%, respectively, for three different concentration levels (0.61 µmol L(-1), 6.1 µmol L(-1) and 12.2 µmol L(-1)). According to the study of electrochemical behavior, ECL behavior and ECL emission spectrum of Ru(bpy)3(2+)/tiopronin system, a possible ECL mechanism was proposed.

Flow injection analysis of thiamazole based on strong Ru(bpy)3 (2+) co-reactant electrochemiluminescence.

Based on the strong electrochemiluminescence (ECL) reaction between thiamazole and tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)3 (2+) ), a sensitive, simple and rapid flow injection analysis method for the determination of thiamazole was developed. When a Pt working electrode was maintained at a potential of +1.50 V (vs Ag/AgCl) in pH 12.0 H3 PO4 -NaOH solution containing thiamazole and Ru(bpy)3 (2+) at a flow rate of 1.0 mL/min, a linear range of 2.0 × 10(-7) -1.0 × 10(-4) mol/L with a detection limit of 5.0 × 10(-8) mol/L was obtained for the detection of thiamazole. The method showed good reproducibility with a relative standard deviation (RSD) of 0.75%. The method has been successfully applied to the determination of thiamazole in spiked animal feeds. In addition, a co-reactant ECL mechanism was proposed for the thiamazole-Ru(bpy)3 (2+) system.

Intra-myocardial injection of both growth factors and heart derived Sca-1+/CD31- cells attenuates post-MI LV remodeling more than does cell transplantation alone: neither intervention enhances functionally significant cardiomyocyte regeneration.

Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are two potent cell survival and regenerative factors in response to myocardial injury (MI). We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31- cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31- cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD) ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV) function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/CD31- cells formed viable grafts and improved LV ejection fraction (EF) (Control, 54.5+/-2.4; MI, 17.6+/-3.1; Cell, 28.2+/-4.2, n = 9, P<0.01). IGF+HGF significantly enhanced the benefits of cell transplantation as evidenced by increased EF (38.8+/-2.2; n = 9, P<0.01) and attenuated adverse structural remodeling. Furthermore, IGF+HGF supplementation increased the cell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31- cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31- cells revealed that Sca-1+/CD31- cells highly expressed various trophic factor mRNAs and IGF+HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis.

ATP-binding cassette transporter Abcg2 lineage contributes to the cardiac vasculature after oxidative stress.

Due to their specialized location, stem and progenitor cells are often exposed to oxidative stress. Although ATP-binding cassette transporter subfamily G member 2 (Abcg2)-expressing cells have been implicated in cardiac protective mechanisms involving oxidative stress, there remains a lack of understanding regarding the behavior of cardiac Abcg2-expressing cells when exposed to ROS. The aim of the present study was to characterize the response of the cardiac Abcg2 lineage to oxidative stress. In vitro analysis demonstrated that the antioxidant program regulated by Abcg2 is dependent on a functional transporter. Delivery of paraquat dichloride (PQ), a systemic oxidative stress-inducing agent, to mice confirmed that Abcg2 provides a survival benefit. When exposed to PQ, reporter mice showed an increase in the Abcg2 lineage. Transcriptional and immunohistochemical analysis of Abcg2 lineage-positive cells revealed an enhanced vascular commitment after stress. Finally, preconditioning with PQ demonstrated a reduction in scar size and an increase in angiogenesis after permanent left coronary artery ligation. In conclusion, the data suggest that Abcg2 plays a cytoprotective role in response to in vivo oxidative stress. The contribution of the Abcg2 lineage to the vasculature in the heart is increased after PQ delivery.

Capillary electrophoresis coupled with electrochemiluminescence detection for the separation and determination of thyreostatic drugs in animal feed.

A rapid, simple, and practical method for the determination of four of the most used thyreostatic drugs (methimazole, 2-thiouracil, 6-methyl-2-thiouracil, and 6-propyl-2-thiouracil) using CE coupled to electrochemiluminescence detection has been established, based on the electrochemiluminescence enhancement of tris(2,2-bipyridyl)ruthenium(II) with these analytes. Parameters that affect separation and detection were optimized. Under the optimum experimental conditions, the four analytes could be well separated within 11 min at the separation voltage of 16 kV in a running solution containing 20 mM phosphate buffer (pH 9.0) and 1.0 × 10(-4) M Ru(bpy)(3)(2+), with a solution of 20 mM phosphate buffer (pH 12.0) containing 1.0 × 10(-4) M Ru(bpy)(3)(2+) in the electrochemiluminescence detection cell. The detection limits for methimazole, 6-methyl-2-thiouracil, 6-propyl-2-thiouracil, and 2-thiouracil were 0.1, 0.05, 0.05, and 0.01 µM, respectively. The proposed method was applied to analyze these drugs in spiked animal feed samples. The recoveries were 88.2∼99.0 and 86.4∼98.7% for the intraday and interday analyses, respectively. The RSDs were 2.7∼4.8 and 1.8∼5.0% for the intraday and interday analyses, respectively. The results demonstrate that the proposed method has promising applications in the detection of thyreostatic drugs in animal feeds.

A tubular one-dimensional polymer constructed from alternating clusters of europium(III)-water and copper(I) chloride bridged by 4-(pyridin-4-yl)benzoate.

A new 3d-4f heterometallic polymer, poly[[aqua-µ3-chlorido-[µ3-4-(pyridin-4-yl)benzoato]tris[µ2-4-(pyridin-4-yl)benzoato]dicopper(I)erbium(III)] dihydrate], {[Cu2Er(C12H8NO2)4Cl(H2O)]·2H2O}n, was synthesized by the hydrothermal reaction of Er2O3, CuCl2·2H2O and 4-(pyridin-4-yl)benzoic acid in the presence of HClO4. The asymmetric unit contains one Er(3+) cation, two Cu(+) cations, one Cl(-) anion, four deprotonated 4-(pyridin-4-yl)benzoate ligands, one coordinated aqua ligand and two solvent water molecules. This tubular one-dimensional polymer is constructed from alternating clusters of europium(III)-water and copper(I) chloride bridged by 4-(pyridin-4-yl)benzoate ligands. Extensive hydrogen-bonding interactions involving both the coordinated and the solvent water molecules provide further stabilization to the structure.

Poly[[tetra-aqua-di-µ(4)-oxalato-µ(2)-oxalato-dineo-dymium(III)] dihydrate].

The title compound, {[Nd(2)(C(2)O(4))(3)(H(2)O)(4)]·2H(2)O}(n), was synthesized hydro-thermally in the presence of bis-(carb-oxy-ethyl-germanium) sesquioxide. It is isostructural with the corresponding Pr compound [Yang et al. (2009). Acta Cryst. E65, m1152-m1153]. The Nd(3+) cation is nine-coordinated and its coordination polyhedron can be described as a distorted tricapped trigonal prism. Two Nd(3+) ions are connected by two O atoms from two oxalate ions to give a dinuclear Nd(2) unit. The unit is further linked to four others via four oxalate ions yielding a layerparallel to (0-11). The linkages between the layers by neighbouring oxalate anions lead to a three-dimensional framework with channels along the c axis. The coordinating and free water mol-ecules are located in the channels and make contact with each other and the host framework by weak O-H⋯O hydrogen bonds.

Aging Kit mutant mice develop cardiomyopathy.

Both bone marrow (BM) and myocardium contain progenitor cells expressing the c-Kit tyrosine kinase. The aims of this study were to determine the effects of c-Kit mutations on: i. myocardial c-Kit(+) cells counts and ii. the stability of left ventricular (LV) contractile function and structure during aging. LV structure and contractile function were evaluated (echocardiography) in two groups of Kit mutant (W/Wv and W41/W42) and in wild type (WT) mice at 4 and 12 months of age and the effects of the mutations on LV mass, vascular density and the numbers of proliferating cells were also determined. In 4 month old Kit mutant and WT mice, LV ejection fractions (EF) and LV fractional shortening rates (FS) were comparable. At 12 months of age EF and FS were significantly decreased and LV mass was significantly increased only in W41/W42 mice. Myocardial vascular densities and c-Kit(+) cell numbers were significantly reduced in both mutant groups when compared to WT hearts. Replacement of mutant BM with WT BM at 4 months of age did not prevent these abnormalities in either mutant group although they were somewhat attenuated in the W/Wv group. Notably BM transplantation did not prevent the development of cardiomyopathy in 12 month W41/W42 mice. The data suggest that decreased numbers and functional capacities of c-Kit(+) cardiac resident progenitor cells may be the basis of the cardiomyopathy in W41/W42 mice and although defects in mutant BM progenitor cells may prove to be contributory, they are not causal.

A fibrin patch-based enhanced delivery of human embryonic stem cell-derived vascular cell transplantation in a porcine model of postinfarction left ventricular remodeling.

It is unknown how to use human embryonic stem cell (hESC) to effectively treat hearts with postinfarction left ventricular (LV) remodeling. Using a porcine model of postinfarction LV remodeling, this study examined the functional improvement of enhanced delivery of combined transplantation of hESC-derived endothelial cells (ECs) and hESC-derived smooth muscle cells (SMCs) with a fibrin three-dimensional (3D) porous scaffold biomatrix. To facilitate tracking the transplanted cells, the hESCs were genetically modified to stably express green fluorescent protein and luciferase (GFP/Luc). Myocardial infarction (MI) was created by ligating the first diagonal coronary artery for 60 minutes followed by reperfusion. Two million each of GFP/Luc hESC-derived ECs and SMCs were seeded in the 3D porous biomatrix patch and applied to the region of ischemia/reperfusion for cell group (MI+P+C, n = 6), whereas biomatrix without cell (MI+P, n = 5), or saline only (MI, n = 5) were applied to control group hearts with same coronary artery ligation. Functional outcome (1 and 4 weeks follow-up) of stem cell transplantation was assessed by cardiac magnetic resonance imaging. The transplantation of hESC-derived vascular cells resulted in significant LV functional improvement. Significant engraftment of hESC-derived cells was confirmed by both in vivo and ex vivo bioluminescent imaging. The mechanism underlying the functional beneficial effects of cardiac progenitor transplantation is attributed to the increased neovascularization. These findings demonstrate a promising therapeutic potential of using these hESC-derived vascular cell types and the mode of patch delivery.