Stem cells for the heart

Cardiovascular disease is one of the major health concerns of modern societies. In the United States in the year 2001 alone, an estimated 64 million people had had one or more forms of cardiovascular disease, claiming almost one million liyes, 38.5 percent of all deaths (American Heart Association).

The Expression of Estrogen Receptor is Dependent on the Estrogen Level and Associated with Cholesterol - Rich Diet in Female Rat's Heart and Vascular Endothelial Cells

Objective To study the effects of estrogen level and cholesterol - rich diet on the expression of estrogen receptor (ER) in cardiovascular tissues including vascular endothelial cells (VEC) of female rats. Methods The receptor binding assay (RBA) was adopted to measure the estrogen receptor level in aortic wall, heart and vascular endothelial cells of female rats on a cholesterol - rich diet. A ra-dioimmunoassay was employed to measure the level of serum estradiol. Results The number of ER significantly decreased in hearts, aorta and vascular endothelial cells in the ovariectomized rats and the rats on a cholesterol - rich diet. In contrast, the administration of estrogen somewhat restored the expression of ER. Conclusions For female rats, the level of estrogen affects the expression of ER in cardiovascular system. The number of ER decreases along with the decrease in the level of estrogen. A cholesterol - rich diet also can decrease the expression of ER in cardiovascular system of female rats.

Noise-induced synchronous stochastic oscillations in small scale cultured heart-cell networks

This paper reports that the synchronous integer multiple oscillations of heart-cell networks or clusters are observed in the biology experiment. The behaviour of the integer multiple rhythm is a transition between super- and sub- threshold oscillations, the stochastic mechanism of the transition is identified. The similar synchronized oscillations are theoretically reproduced in the stochastic network composed of heterogeneous cells whose behaviours are chosen as excitable or oscillatory states near a Hopf bifurcation point. The parameter regions of coupling strength and noise density that the complex oscillatory rhythms can be simulated are identified. The results show that the rhythm results from a simple stochastic alternating process between super- and sub-threshold oscillations. Studies on single heart cells forming these clusters reveal excitable or oscillatory state nearby a Hopf bifurcation point underpinning the stochastic alternation. In discussion, the results are related to some abnormal heartbeat rhythms such as the sinus arrest.

Autoantibodies against G-Protein-Coupled Receptors Modulate Heart Mast Cells

Mast cells are believed to be involved in myocardial tissue remodelling under pathophysiological conditions. We examined the effects of autoantibodies against G-protein-coupled receptors in sera of patients with heart diseases on myocardial mast cells in the cultured neonatal Sprague-Dawley rat heart cells. Cells collected at day 3 and 10 of the culture were preincubated with autoantibodies against α-adrenoceptor and angiotensin Ⅱ ATl-receptor, agonist phenylephrine and angiotensin Ⅱ, and control IgG. The pretreated cultured cells were stained for selected mast cell markers tryptase, chymase and TNF-α The cultured cells were also processed for observation with electron microscopy. The autoantibodies-treatment of the 3-day cultured cells caused both increased intensity of immunofluorescence （p 〈 0.05） and their enlarged diameters of the mast cells when compared to age-matched ones. In contrast, the fluorescence of preincubated 10-day-old mast cells was decreased compared with controls （p 〈 0.01）. In control samples, the fluorescence of 10-day-old mast cells was significantly higher than that of 3-day-old ones （p 〈 0.001）. Results of electron microscopy examination demonstrated there was an increased granulation of treated 3-day-old mast cells, while a degranulation of mast cells at day 10 of application. The results suggest the modulation effect of the autoantibodies against G-protein-coupled receptors on mast cells, indicating a potential functional link between the autoantibodies against G-protein-coupled receptors and the mast cells in progression of heart disease.

Septation and shortening of outflow tract in embryonic mouse heart involve changes in cardiomyocyte phenotype and α-SMA positive cells in the endocardium

Background Studies on human, rat and chicken embryos have demonstrated that during the period of outflow tract septation, retraction of the distal myocardial margin of the outflow tract from the junction with aortic sac to the level of semilunar valves leads to the shortening of the myocardial tract. However, the mechanism is not clear. So we investigated the mechanism of outflow tract shortening and remodeling and the spatio-temporal distribution pattern of α-SMA positive cells in the outflow tract cushion during septation of the outflow tract in the embryonic mouse heart Methods Serial sections of mouse embryos from embryonic day 9 (ED 9) to embryonic day 16 (ED 16) were stained with monoclonal antibodies against α-SCA, α-SMA, or desmin, while apoptosis was assessed using the terminal deoxyribonucleotidy transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay Results Between ED 11 and ED 12, the cardiomyocytes in the distal portion of the outflow tract were observed losing their myocardial phenotype without going into apoptosis, suggesting that trans-differentiation of cardiomyocytes into the cell components of the free walls of the intrapericardial ascending aorta and pulmonary trunk The accumulation of α-SMA positive cells in the cardiac jelly began on ED 10 and participated in the ridge fusion and septation of the outflow tract Fusion of the distal ridges resulted in the formation of the facing walls of the intrapericardial ascending aorta and pulmonary trunk Fusion of the proximal ridges was accompanied by the accumulation of α-SMA positive cells into a characteristic central whorl, in which cell apoptosis could be observed Subsequent myocardialization resulted in the formation of the partition between the subaortic and subpulmonary vestibules Conclusions The shortening of the embryonic heart outflow tract in mice may result not from apoptosis, but from the trans-differentiation of cells with cardiomyocyte phenotype in the distal portion of the outflow tract into the cell components of the free walls of the intrapericardial ascending aorta and pulmonary trunk The primary roles of α-SMA positive cells in the septation and remodeling of the outflow tract may assure proper fusion of the outflow ridges and form the facing walls of the intrapericardial ascending aorta and pulmonary trunk

Heart Valves Grown from Womb Fluid Cells

科学家们首次从人体子宫的流体细胞中培育出了人类的心瓣膜,这一发现为有先天心脏缺陷的患者带来了福音。这种由自身组织培植的心瓣膜被移植入人体后,其性能将比人工心脏或者通过器官捐献而来的心脏更持久有效;并且,此项研究的前期动物试验已经成功。

Detection of p53 gene mutations in skeletal muscle cell of patients with chronic heart failure

Progressive deterioration of physical work capacity in congestive heart failure (CHF) is often attributed to ongoing skeletal muscle atrophy and abnormalities in muscle metabolism. The purpose of the present study was to investigate if mutations in the p53 gene thought to be a promotor of apoptosis are involved in intrinsic apoptotic abnormalities in skeletal muscle of patients (pts) with CHF. Percutaneous needle biopsy from the m. vastus lateralis were obtained from 19 pts with CHF (LV EF 25%±10%). Single strand confirmation polymorphism analysis of polymerase chain reation products (PCR SSCP analysis) was used for detection of mutations in exon 5 8 of the p53 gene in skeletal Heart Center, University Leipzig, Germany (Yu JT, Adams V, Fiehn E, Schuler G and Hambrecht R) Institut of Pathology, University Freiburg, Germany (Ye J and Riede U)muscle cells. Four of 19 muscle specimens (21%) showed mobility shifts. To characterize the nuleotide sequence alterations specimens were examined further by direct sequence analysis of PCR product. Two of four specimens showing a band shift in the SSCP analysis exhibited a mutated p53 sequence. Sequence analysis revealed that these alteratons were point mutation exon 8 (14482, G→A) and deletion in exon 5 (13143 13157). A high frequency of p53 mutations was detected in skeletal muscle cells of patients with chronic heart failure. These findings suggest a role for apoptosis in the progression of intrinsic skeletal muscle abnormalities and consequently of exercise intolerance in chronic heart failure.