Dynamical systems analysis of arterial blood pressure signals in relation to heart rate fluctuations in chick embryos

We attempted a new approach based on a modern dynamical system theory to reconstruct the arterial blood pressure signals in relation to heart rate fluctuations of developing chick embryos. The dynamical systems approach in general is to model a phenomenon that is presented by a single time series record and approximate the dynamical property (e.g. heart rate fluctuations) of a system based only on information contained in a single-variable (arterial blood pressure) of the system. The time-series data of the arterial blood pressure was reconstructed in 3-dimensional space to draw characteristic orbits. Since the reconstructed orbits of the blood pressure should retain information contained in the pressure signals, we attempted to derive instantaneous heart rate (IHR) from the reconstructed orbits. The derived IHR presenting HR fluctuations coincided well with the IHR obtained conventionally from the peak-to-peak time intervals of the maximum blood pressure. Movements of the reconstructed orbits of the arterial blood pressure in 3-dimensional space reflected HR fluctuations (i.e. transient decelerations and accelerations).     

华法令诱导大鼠体内主动脉的钙化作用

目的:研究华法令对大鼠体内主动脉的钙化作用。方法:采用华法令(3 mg/g饲料)的饲料喂养诱导大鼠体内动脉钙化。实验分3组(n=6),对照组、6 W钙化组、12 W钙化组。Von Kossa染色观察钙结节形成,邻甲酚酞络合酮比色法定量测定钙沉积含量。采用TUNEL染色法检测大鼠主动脉组织内血管平滑肌细胞(Vascular Smooth Muscle Cell,VSMC)凋亡。Western blot法检测大鼠主动脉组织中生长抑制特异蛋白6(Growth Arrest Specific Gene 6 Protein,Gas 6)蛋白表达水平。结果:钙化组钙结节、钙沉积含量及VSMC凋亡均高于对照组(P0.01)有显著差异。钙化形成与凋亡表达呈显著正相关(R2=0.8853,P0.0001);钙化组Gas 6蛋白表达量较对照组下调(P0.01)有显著差异。结论:华法令通过下调Gas 6蛋白诱导大鼠体内主动脉钙化形成。     

HO-1 modified mesenchymal stem cells modulate MMPs/TIMPs system and adverse remodeling in infarcted myocardium

The present study was to determine the effects of the heme oxygenase-1 (HO-1) modified mesenchymal stem cells (MSCs) transplantation into acute MI hearts on normalizing the ratio of MMPs/TIMPs and remodeling in infarcted myocardium. HO-1 was transfected into cultured MSCs using an adenoviral vector. 1 × 10⁶ Ad-HO-1-transfected MSCs (HO-1-MSCs) or Ad-Null-transfected MSCs (Null-MSCs) or PBS was respectively injected into rat hearts 1 h intramyocardially after myocardial infarction. The cardiac performance was significantly improved and left ventricular dilatation was significantly attenuated in HO-1-MSCs transplanted hearts. Moreover, a significant increase in microvessel density was observed in HO-1-MSCs transplanted hearts. TIMP2,3 expression in HO-1-MSCs transplanted hearts was significantly increased, and MMP2,9 expression in HO-1-MSCs transplanted hearts was significantly lower than Null-MSCs transplanted and PBS-treated hearts. TIMP1 expression did not vary significantly. Null-MSCs transplantation did not decrease the expression of MMP2,9 significantly compared with PBS-treated hearts. The ratio of TIMP2 to MMP2, and TIMP3 to MMP9 in cell-grafted hearts was increased significantly. HO-1-MSCs transplantation normalize the ratio of MMPs/TIMPs, contributing to the reversion of myocardial extracellular remodeling.     

Malnutrition enhances cardiovascular responses to chemoreflex activation in awake rats

Several studies in the literature suggest that low-protein intake is associated with increases in sympathetic efferent activity and cardiovascular disease. Among the possible mechanisms, changes in the neurotransmission of cardiovascular reflexes have been implicated. Therefore, the present study comprised the evaluation of chemoreflex responsiveness in rats subjected to a low-protein diet during the 35 days after weaning. As a result, we observed that malnourished rats presented higher levels of baseline mean arterial pressure and heart rate and exhibited a mild increase in the pressor response to chemoreflex activation. They also exhibited a massive bradycardic response to chemoreflex activation. Interestingly, bilateral ligature of the carotid body arteries further increased baseline mean arterial pressure and heart rate in malnourished animals. The data suggest severe autonomic imbalance and/or change in the central interplay between neural and cardiovascular mechanisms.     

Age-related changes in microarchitecture and mineralization of cancellous bone in the porcine mandibular condyle

The mandibular condyle is considered a good model for developing cancellous bone because of its rapid growth and high rate of remodeling. The aim of the present study was to analyze the simultaneous changes in microarchitecture and mineralization of cancellous bone during development in a three-dimensional fashion. Eight mandibular condyles of pigs aged 8 weeks prepartum to 108 weeks postpartum were scanned using microCT with an isotropic spatial resolution of 10 microm. The number of trabeculae decreased during development, whereas both the trabecular thickness and the distance between the trabeculae increased. The bone surface to volume ratio decreased during development, possibly limiting the amount of (re)modeling. Both the mean degree of mineralization and intratrabecular differences in mineralization between the surfaces and cores of trabecular elements increased during development. The trabecular surfaces were more highly mineralized in the older condyles compared to the younger ones. Together with the observed decrease in the relative size of trabecular surface, this finding suggests a decrease in (re)modeling activity during development. In accordance with the general growth and development of the pig, it was concluded that most developmental changes in cancellous bone occur until the age of 40 weeks postpartum.     

肝素结合性表皮生长因子在心肌重塑中的作用

肝素结合性表皮生长因子（HB-EGF）是表皮生长因子家族成员之一。HB-EGF是多种细胞的有丝分裂原,参与一系列生理和病理过程,包括心肌细胞肥大,成纤维细胞增生,胶原纤维表达增多,是心肌重塑发生发展过程中的一个重要生长因子。本文综述了HB-EGF在心肌重塑过程中的研究进展。     

VIP and endothelin receptor antagonist: An effective combination against experimental pulmonary arterial hypertension

Background

Pulmonary Arterial Hypertension (PAH) remains a therapeutic challenge, and the search continues for more effective drugs and drug combinations. We recently reported that deletion of the vasoactive intestinal peptide (VIP) gene caused the spontaneous expression of a PH phenotype that was fully corrected by VIP. The objectives of this investigation were to answer the questions: 1) Can VIP protect against PH in other experimental models? and 2) Does combining VIP with an endothelin (ET) receptor antagonist bosentan enhance its efficacy?

Methods

Within 3 weeks of a single injection of monocrotaline (MCT, s.c.) in Sprague Dawley rats, PAH developed, manifested by pulmonary vascular remodeling, lung inflammation, RV hypertrophy, and death within the next 2 weeks. MCT-injected animals were either untreated, treated with bosentan (p.o.) alone, with VIP (i.p.) alone, or with both together. We selected this particular combination upon finding that VIP down-regulates endothelin receptor expression which is further suppressed by bosentan. Therapeutic outcomes were compared as to hemodynamics, pulmonary vascular pathology, and survival.

Results

Treatment with VIP, every other day for 3 weeks, begun on the same day as MCT, almost totally prevented PAH pathology, and eliminated mortality for 45 days. Begun 3 weeks after MCT, however, VIP only partially reversed PAH pathology, though more effectively than bosentan. Combined therapy with both drugs fully reversed the pathology, while preventing mortality for at least 45 days.

Conclusions

1) VIP completely prevented and significantly reversed MCT-induced PAH; 2) VIP was more effective than bosentan, probably because it targets a wider range of pro-remodeling pathways; and 3) combination therapy with VIP plus bosentan was more effective than either drug alone, probably because both drugs synergistically suppressed ET-ET receptor pathway.     

Phenotypic heterogeneity influences the behavior of rat aortic smooth muscle cells in collagen lattice

Phenotypic modulation of vascular smooth muscle cells (SMCs) in atherosclerosis and restenosis involves responses to the surrounding microenvironment. SMCs obtained by enzymatic digestion from tunica media of newborn, young adult (YA) and old rats and from the thickened intima (TI) and underlying media of young adult rat aortas 15 days after ballooning were entrapped in floating populated collagen lattice (PCL). TI-SMCs elongated but were poor at PCL contraction and remodeling and expressed less alpha2 integrin compared to other SMCs that appeared more dendritic. During early phases of PCL contraction, SMCs showed a marked decrease in the expression of alpha-smooth muscle actin and myosin. SMCs other than TI-SMCs required 7 days to re-express alpha-smooth muscle actin and myosin. Only TI-SMCs in PCL were able to divide in 48 h, with a greater proportion in S and G2-M cell cycle phases compared to other SMCs. Anti-alpha2 integrin antibody markedly inhibited contraction but not proliferation in YA-SMC-PLCs; anti-alpha1 and anti-alpha2 integrin antibodies induced a similar slight inhibition in TI-SMC-PCLs. Finally, TI-SMCs rapidly migrated from PCL on plastic reacquiring their epithelioid phenotype. Heterogeneity in proliferation and cytoskeleton as well the capacity to remodel the extracellular matrix are maintained, when SMCs are suspended in PCLs.     

Sphingosine 1-phosphate inhibits migration and RANTES production in human bronchial smooth muscle cells

Sphingosine 1-phosphate (S1P), a bioactive lipid mediator, has been shown to be increased in bronchoalveolar lavage fluid after allergen challenge in asthmatic patients. Here, we examined S1P actions and their intracellular signalings in cultured human bronchial smooth muscle cells (BSMCs). Expression of mRNAs of three subtypes of S1P receptors, including S1P(1), S1P(2), and S1P(3), was detected in BSMCs, and exposure of the cells to S1P inhibited platelet-derived growth factor (PDGF)-induced migration and tumor necrosis factor-alpha-induced RANTES production. S1P also inhibited PDGF-induced Rac1 activation, and dominant negative Rac1 inhibited PDGF-induced migration. On the other hand, dominant negative Galpha(q) attenuated the S1P-induced inhibition of RANTES production. Finally, an S1P(2)-selective antagonist, JTE-013, suppressed the S1P-induced inhibition of migration response and RANTES production. These results suggest that S1P attenuates cell migration by inhibiting a Rac1-dependent signaling pathway and decreases RANTES production by stimulating a Galpha(q)-dependent mechanism both possibly through the S1P(2) receptors.