Exploration and Validation of Immune and Therapeutic-Related Hub Genes in Aortic Valve Calcification and Carotid Atherosclerosis.

Background: Cardiovascular diseases, such as aortic valve calcification (AVC) and carotid atherosclerosis (CAS), impose substantial health challenges on a global scale. Both disorders have overlapping risk factors, which might trigger similar immune-inflammatory reactions in both diseases. Methods: Shared differentially expressed genes (DEGs) were identified in the AVC and CAS datasets from the Gene Expression Omnibus (GEO). Candidate hub genes associated with immunity were identified using LASSO and immune cell infiltration analysis, and single gene set enrichment analysis (GSEA) was performed on the datasets. Subsequently, the hub genes were confirmed by qRT‒PCR validation in tissue samples. Results: A total of 140 upregulated and 65 downregulated common genes were screened. Enrichment analyses highlighted immune system processes, response to stress, and cytokine pathways among the identified CEGs. LASSO identified candidate hub genes, including ANGPTL1, CX3CR1, and CCL4. Immune cell infiltration analysis emphasized the participation of immune cells, including macrophages, γδ T cells, and resting NK cells. The three hub genes were validated by qRT‒PCR analysis. Conclusion: Our study explored immunological processes, including immune-related genes and cells, involved in the development of AVC and CAS. In particular, the identified hub genes ANGPTL1, CX3CR1, and CCL4 play crucial roles in mediating immune-inflammatory responses, which are central to the pathogenesis of these cardiovascular diseases, and the involvement of these genes in key immune pathways suggests that they could serve as potential biomarkers for early diagnosis or as targets for therapeutic strategies.

Research on Unsupervised Low-Light Railway Fastener Image Enhancement Method Based on Contrastive Learning GAN.

The railway fastener, as a crucial component of railway tracks, directly influences the safety and stability of a railway system. However, in practical operation, fasteners are often in low-light conditions, such as at nighttime or within tunnels, posing significant challenges to defect detection equipment and limiting its effectiveness in real-world scenarios. To address this issue, this study proposes an unsupervised low-light image enhancement algorithm, CES-GAN, which achieves the model's generalization and adaptability under different environmental conditions. The CES-GAN network architecture adopts a U-Net model with five layers of downsampling and upsampling structures as the generator, incorporating both global and local discriminators to help the generator to preserve image details and textures during the reconstruction process, thus enhancing the realism and intricacy of the enhanced images. The combination of the feature-consistency loss, contrastive learning loss, and illumination loss functions in the generator structure, along with the discriminator loss function in the discriminator structure, collectively promotes the clarity, realism, and illumination consistency of the images, thereby improving the quality and usability of low-light images. Through the CES-GAN algorithm, this study provides reliable visual support for railway construction sites and ensures the stable operation and accurate operation of fastener identification equipment in complex environments.

Risk prediction model construction for post myocardial infarction heart failure by blood immune B cells.

Background: Myocardial infarction (MI) is a common cardiac condition with a high incidence of morbidity and mortality. Despite extensive medical treatment for MI, the development and outcomes of post-MI heart failure (HF) continue to be major factors contributing to poor post-MI prognosis. Currently, there are few predictors of post-MI heart failure. Methods: In this study, we re-examined single-cell RNA sequencing and bulk RNA sequencing datasets derived from the peripheral blood samples of patients with myocardial infarction, including patients who developed heart failure and those who did not develop heart failure after myocardial infarction. Using marker genes of the relevant cell subtypes, a signature was generated and validated using relevant bulk datasets and human blood samples. Results: We identified a subtype of immune-activated B cells that distinguished post-MI HF patients from non-HF patients. Polymerase chain reaction was used to confirm these findings in independent cohorts. By combining the specific marker genes of B cell subtypes, we developed a prediction model of 13 markers that can predict the risk of HF in patients after myocardial infarction, providing new ideas and tools for clinical diagnosis and treatment. Conclusion: Sub-cluster B cells may play a significant role in post-MI HF. We found that the STING1, HSPB1, CCL5, ACTN1, and ITGB2 genes in patients with post-MI HF showed the same trend of increase as those without post-MI HF.

Outcomes of Cerebral Embolic Protection for Bicuspid Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Replacement.

Background There was limited high-quality evidence that illuminated the efficiency of cerebral embolic protection (CEP) use during transcatheter aortic valve replacement (TAVR) for bicuspid aortic valve (BAV) stenosis. Methods and Results In this retrospective cohort study, patients with BAV stenosis undergoing TAVR with or without CEP were identified by querying the National Inpatient Sample database. The primary end point was any stroke during the hospitalization. The composite safety end point included any in-hospital death and stroke. We applied propensity score-matched analysis to minimize standardized mean differences of baseline variables and compare in-hospital outcomes. From July 2017 to December 2020, 4610 weighted hospitalizations with BAV stenosis undergoing TAVR were identified, of which 795 were treated with CEP. There was a significant increase in the CEP use rate for BAV stenosis (P-trend <0.001). A total of 795 discharges with CEP use were propensity score matched to 1590 comparable discharges but without CEP. CEP use was associated with a lower incidence of in-hospital stroke (1.3% versus 3.8%; P<0.001), which in multivariable regression was also independently associated with the primary outcome (adjusted odds ratio=0.38 [95% CI, 0.18-0.71]; P=0.005) and the safety end point (adjusted odds ratio=0.41 [95% CI, 0.22-0.68] P=0.001). Meanwhile, no significant difference was found in the cost of hospitalization ($46 629 versus $45 147; P=0.18) or the risk of vascular complications (1.9% versus 2.5%; P=0.41). Conclusions This observational study supported CEP use for BAV stenosis, which was independently associated with less in-hospital stroke without burdening the patients with a high hospitalization cost.

WGCNA combined with machine learning algorithms for analyzing key genes and immune cell infiltration in heart failure due to ischemic cardiomyopathy.

Background: Ischemic cardiomyopathy (ICM) induced heart failure (HF) is one of the most common causes of death worldwide. This study aimed to find candidate genes for ICM-HF and to identify relevant biomarkers by machine learning (ML). Methods: The expression data of ICM-HF and normal samples were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between ICM-HF and normal group were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and gene ontology (GO) annotation analysis, protein-protein interaction (PPI) network, gene pathway enrichment analysis (GSEA), and single-sample gene set enrichment analysis (ssGSEA) were performed. Weighted gene co-expression network analysis (WGCNA) was applied to screen for disease-associated modules, and relevant genes were derived using four ML algorithms. The diagnostic values of candidate genes were assessed using receiver operating characteristic (ROC) curves. The immune cell infiltration analysis was performed between the ICM-HF and normal group. Validation was performed using another gene set. Results: A total of 313 DEGs were identified between ICM-HF and normal group of GSE57345, which were mainly enriched in biological processes and pathways related to cell cycle regulation, lipid metabolism pathways, immune response pathways, and intrinsic organelle damage regulation. GSEA results showed positive correlations with pathways such as cholesterol metabolism in the ICM-HF group compared to normal group and lipid metabolism in adipocytes. GSEA results also showed a positive correlation with pathways such as cholesterol metabolism and a negative correlation with pathways such as lipolytic presentation in adipocytes compared to normal group. Combining multiple ML and cytohubba algorithms yielded 11 relevant genes. After validation using the GSE42955 validation sets, the 7 genes obtained by the machine learning algorithm were well verified. The immune cell infiltration analysis showed significant differences in mast cells, plasma cells, naive B cells, and NK cells. Conclusion: Combined analysis using WGCNA and ML identified coiled-coil-helix-coiled-coil-helix domain containing 4 (CHCHD4), transmembrane protein 53 (TMEM53), acid phosphatase 3 (ACPP), aminoadipate-semialdehyde dehydrogenase (AASDH), purinergic receptor P2Y1 (P2RY1), caspase 3 (CASP3) and aquaporin 7 (AQP7) as potential biomarkers of ICM-HF. ICM-HF may be closely related to pathways such as mitochondrial damage and disorders of lipid metabolism, while the infiltration of multiple immune cells was identified to play a critical role in the progression of the disease.

Exploration and validation of the influence of angiogenesis-related factors in aortic valve calcification.

Over the years, bioinformatics tools have been used to identify functional genes. In the present study, bioinformatics analyses were conducted to explore the underlying molecular mechanisms of angiogenic factors in calcific aortic valve disease (CAVD). The raw gene expression profiles were from datasets GSE153555, GSE83453, and GSE51472, and the angiogenesis-related gene set was from the Gene Set Enrichment Analysis database (GSEA). In this study, R was used to screen for differentially expressed genes (DEGs) and co-expressed genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) Pathway enrichment analysis were performed on DEGs and validated in clinical samples. DEGs in CAVD were significantly enriched in numerous immune response pathways, inflammatory response pathways and angiogenesis-related pathways. Nine highly expressed angiogenesis-related genes were identified, of which secretogranin II (SCG2) was the most critical gene. MiRNA and transcription factors (TFs) networks were established centered on five DEGs, and zinc finger E-box binding homeobox 1 (ZEB1) was the most important transcription factor, verified by PCR, immunohistochemical staining and western blotting experiments. Overall, this study identified key genes and TFs that may be involved in the pathogenesis of CAVD and may have promising applications in the treatment of CAVD.

Cardiac computed tomography based analysis of mitral annulus, coronary sinus and left circumflex artery in patients with mitral regurgitation: Implications for transcatheter mitral annuloplasty techniques.

INTRODUCTION: CT imaging analysis of mitral annulus (MA), coronary sinus (CS) and left circumflex artery (LCX) is critical to transcatheter mitral annuloplasty (TMA), which, however, is scantly reported. We aimed to comprehensively assess MA, CS and LCX anatomy and geometry in mitral regurgitation (MR) based on 3-D reconstruction of cardiac CT images. METHODS: Patients with primary or secondary MR and patients without MR were recruited and underwent cardiac CT examination. MR severity was evaluated by echocardiography. 3-D reconstruction of cardiac CT images was done by the Mimics Research 21.0 software. A MA-centered two dimensional coordinate system, a CS plane, a MA plane and a series of auxiliary planes along the posterior MA were created for the measurement of parameters defining MA, CS and LCX anatomy and geometry during the cardiac cycle. RESULTS: The secondary MR group had a significantly higher MA perimeter index than the other two groups during the cardiac cycle. The CS diameters at most sites, and the posterior MA radian were substantially greater in the two MR groups. Distances between the CS and MA at some locations were significant different among the three groups. The secondary MR group had a significantly smaller CS-MA plane angle than the other two groups during systole, and than control group during diastole. The site where the CS crossed LCX was pinpointed. CONCLUSION: The comprehensive information from this study may help improve the results of TMA and enhance the design of devices for a better annuloplasty effect.

Primary extraskeletal chondroblastic osteosarcoma of the pericardium: a case report and literature review.

BACKGROUND: Primary extraskeletal chondroblastic osteosarcoma has very poor prognosis, especially in the elderly. The pericardium is an extremely rare site for this tumour. CASE SUMMARY: A 67-year-old man presented with a large pericardial effusion and an intrapericardial mass. His past medical history of pulmonary tuberculosis led us to initially suspect tuberculous pericarditis. Primary extraskeletal chondroblastic osteosarcoma arising from the pericardium was diagnosed by the pathologist after surgery. The patient suffered severe intraoperative blood loss and surgical trauma. He went into shock and died a few hours after surgery. DISCUSSION: Extraskeletal chondroblastic osteosarcoma is a very rare tumour with a grim prognosis. Clinical manifestations frequently are not specific and can be explained by associated pathology. In this report, we describe an unusual case of primary extraskeletal chondroblastic osteosarcoma located in the pericardium and present a review of the literature.

Employing the Sirolimus-Eluting Poly (Propylene Carbonate) Mesh for the Prevention of Arteriovenous Graft Stenosis in Rats.

Poly (propylene carbonate, PPC) is a new member of the aliphatic polyester family. An outstanding feature of PPC is that it produces mainly water and carbon dioxide when degraded in vivo, causing minimal side effects. This unique property together with excellent biocompatibility and biodegradability makes PPC a promising material for drug delivery. In this study, we explored the effect of the sirolimus (an inhibitor of cell growth)-eluting PPC mesh on graft stenosis and its possible mechanisms in a rat arteriovenous grafting model. The PPC mesh was prepared by electrospinning. A jugular vein to abdominal aortic autograft transplantation model was established in rats. The graft was then treated by wrapping with the drug mesh or the drug-free mesh or left untreated. Four weeks posttransplantation, neointima was measured with hematoxylin and eosin staining, matrix metalloproteinase-2 (MMP-2), and MMP-9, and proliferating cell nuclear antigen (PCNA) in the grafts were assayed by Western blotting and immunohistochemistry, respectively. In vitro rat aortic adventitial fibroblast cell (RAAFC) migration was assessed using the Boyden chamber assay, and phospho-mammalian target of rapamycin (mTOR) levels in RAAFCs were determined by Western blotting. Animals with the drug mesh had an intimal area index of 4.87% ± 0.98%, significantly lower than that of the blank group (14.21% ± 2.56%) or the PPC group (15.03% ± 2.35%, both P < .05). The sirolimus mesh markedly suppressed MMP-2 and MMP-9 expression, decreased PCNA-positive cell numbers, inhibited RAAFC migration, and reduced phospho-mTOR levels. Our data suggest that the sirolimus-eluting PPC mesh might be potentially applied for the management of grafting stenosis.

[Expression of cytokines Il-6, IL-34 and M-CSFR in chronic periodontitis and its clinical significance].

PURPOSE: To detect the expression of IL-6，IL-34 and M-CSFR in chronic periodontitis and healthy gingival tissue and discuss the role of IL-6，IL-34 and M-CSFR in the etiology of chronic periodontitis. METHODS: A total of 8 patients with mild chronic periodontitis and 8 patients with severe chronic periodontitis were collected in this study. As control，8 normal gingival tissues from extracted healthy were selected. The expression of IL-6, IL-34 and M-CSFR mRNA was detected by real-time PCR; the expression of IL-6, IL-34 and M-CSFR protein was detected by Western blotting. Statistical analysis was performed using GraphPad Prism 6.0. RESULTS: The levels of IL-6, IL-34, M-CSFR mRNA and protein expression in chronic periodontitis was significantly higher than that of the normal gingival tissue(P<0.05). CONCLUSIONS: IL-6, IL-34 and M-CSFR may be closely related to the development of chronic periodontitis.

Applicability of electrospun polypropylene carbonate polymers as a drug carrier for sirolimus.

Polypropylene carbonate (PPC), a biodegradable aliphatic polyester, exhibits one particular advantage over other polyesters, which is that following degradation in vivo, it primarily produces H2O and CO2, causing minimal side effects. Although PPC exhibits limited mechanical strength, and is therefore not able to serve as a scaffold to support tissue regeneration, it may be suitable for drug delivery; however, this requires further investigation. In the present study, electrospinning was applied to generate PPC polymers containing sirolimus, a cell growth­inhibiting drug which is used to treat restenosis. The properties of PPC­sirolimus polymers were examined using scanning electron microscopy, differential scanning calorimetry and in vitro degradation assays. Drug loading and entrapment efficiency were determined, and in vitro sirolimus­release from the polymer was assessed. Furthermore, the effect of PPC­sirolimus polymers on cell growth was measured using an MTT assay in vitro. The results of the present study demonstrated that electrospun PPC polymers formed a uniform three­dimensional, grid­intertwined, net­like structure; the surface of the polymers was smooth and the diameter was ~3 µm. Differential scanning calorimetry analysis demonstrated that sirolimus existed in an amorphous state in the polymer. Following soaking in PBS for 4 weeks, the polymer swelled and the net­like structure broke down and fragmented. Sirolimus loading and entrapment efficiency were 10.3±3.2 and 95.1±10.6%, respectively. Sirolimus­release from PPC­sirolimus polymers continued for 28 days in PBS. PPC­sirolimus markedly inhibited the growth of rat aortic adventitial fibroblast cells, an effect which was not observed with PPC alone. The results of the present study suggest that PPC polymers are a promising alternative drug carrier for sirolimus.

Transcatheter Closure Versus Repeat Surgery for the Treatment of Postoperative Left-to-Right Shunts: A Single Center 15-Year Experience.

BACKGROUND: Repeat surgery and the percutaneous approach (transcatheter closure (TCC)) have been used for the management of postoperative left-to-right shunts. In this study, we described our 15 years of experience in treating postoperative left-to-right shunts with these two approaches. METHODS: From February 2002 to February 2017, 50 patients with residual left-to-right shunts, following cardiac surgery, were treated using TCC or repeat surgery. Clinical examination, standard 12-lead electrocardiography, chest X-ray, and a transthoracic echocardiogram were performed before hospital discharge and at all follow-ups. RESULTS: The closure rate was 100% in both groups and there was no procedure-related mortality. Patients with TCC had few complications. The procedure time and duration of hospital stay for TCC patients were 58.9 ± 27.7 min and 6.1 ± 0.8 days, respectively. Eleven out of 19 patients receiving reoperation suffered serious complications after surgery, e.g., bleeding and nosocomial infections. The operation time and duration of hospital stay for reoperation patients were 256.7 ± 60.5 min and 17.0 ± 4.0 days, respectively. No other serious complications were seen at all follow-up visits for both groups. CONCLUSIONS: In conclusions, TCC is safe and effective for the management of postoperative left-to-right shunts, and is associated with few complications, which can be the favored closure strategy over repeat surgery for the management of postoperative left-to-right shunts.

Transcatheter closure of calcified patent ductus arteriosus in older adult patients: Immediate and 12-month follow-up results.

OBJECTIVE: To present our experience in transcatheter closure of calcified patent ductus arteriosus (PDA) in older adult patients, which has rarely been reported. PATIENTS: From 2009 to 2014, a total of 16 patients (median age 58 years) with calcified PDA underwent transcatheter closure in our center. All patients were symptomatic with major symptoms being exertional dyspnea (in 12), palpitations (in 8), and fatigue (in 5). A continuous murmur was heard in all patients. The median ductus diameter was 4 mm (range 3-7 mm). The median Qp/Qs was 1.6 (range 1.4-2.9). INTERVENTIONS: Transcatheter closure was performed for all patients. The size of the occluder selected was 2-3 mm greater than the narrowest portion of PDA. We experienced difficulties in advancing the multipurpose catheter through the calcified duct in about one third of patients (5/16). Considering that calcified tissue has a greater tendency to rupture, hence, to close PDA in these patients, they adopted the retrograde wire-assisted technique and modified the procedure to reduce the shear stress of sheath and avoid any sheath kinking. For the remaining 11 patients, the advancement of the multipurpose catheter through the calcified duct was smooth and the conventional antegrade approach was applied. OUTCOME MEASURES: Clinical examination, standard 12-lead electrocardiography, chest x-ray, and transthoracic echocardiography were performed before hospital discharge, at 1-, 3-, 6-, and 12-months follow-ups. RESULTS: All PDAs were successfully closed. There were no deaths. Three patients had a trivial residual shunt, with one also having intravascular hemolysis. Following pharmacological treatment, hemolysis signs vanished at 7 days postprocedure. The trivial residual shunt disappeared in all three patients at 3-month follow-up. No new-onset residual shunt, device embolization, device dislocation, infective endocarditis, or embolism was observed at all follow-up time points. CONCLUSION: Successful closure of calcified PDA with few complications in older adult patients was achieved using the duct occluder.

Successful Closure of a Ventricular Septal Defect Using a Novel Non-Prosthesis Touching Technique Following Mechanical Aortic Valve Replacement.

Percutaneous intervention is preferred over reoperation for the treatment of iatrogenic membranous ventricular septal defects (VSDs). During the standard percutaneous procedure, an arterio-venous loop is used for occluder deployment, entailing the risk of device impingement on the prosthetic aortic valve, which may cause serious complications or even death. In this report, we describe a novel non-prosthesis touching procedure for the closure of a VSD in a patient with prior aortic valve replacement. The unique feature of this technique is the use of an apex-venous loop for occluder deployment, which prevents the device impingement on the prosthetic valve, thus avoiding difficulties, lengthy operation and serious complications associated with the standard procedure. Immediate and 1-year follow-up results showed that the VSD was successfully closed and no serious complications were observed.

Pterostilbene attenuates inflammation in rat heart subjected to ischemia-reperfusion: role of TLR4/NF-κB signaling pathway.

OBJECTIVE: The aim of the present study was to investigate whether pterostilbene could modulate the TLR4/NF-κB signaling, reduce neutrophil accumulation and TNF-α induction in an ischemia/reperfusion injured rat heart model. MATERIALS AND METHODS: Rats were randomly exposed to sham operation, myocardial ischemia and reperfusion (MI/R), MI/R + pterostilbene, MI/R + pterostilbene + L-NAME. And myocardial infarct size, apoptosis, TLR4 expression, NF-κB expression, MPO level and TNF-α level were detected. RESULTS: The results demonstrated that after MI/R, the expressions of myocardial TLR4, NF-κB and caspase-3 increased significantly in ischemia area. Compared with MI/R, pterostilbene significantly attenuated the expressions of TLR4, NF-κB and caspase-3. In addition, it also reduced myeloperoxidase (MPO) levels, both serum and myocardial TNF-α production, myocardial infarct sizes (INF/AAR%) and myocardial apoptosis induced by MI/R. All the effects of pterostilbene were abolished by L-NAME, a nitric oxide synthase inhibitor. CONCLUSION: These data provide evidence that pterostilbene inhibits TLR4/NF-κB signaling and apoptosis in the rat heart subjected to MI/R, which is associated with NO production.

[Efficacy observation of auditory reconstruction using three different materials in ossiculoplasty and mastoidectomy to treat chronic otitis media].

OBJECTIVE: To study the effects of different types of prosthesis used in ossiculoplasty on mastoidectomy of treating chronic otitis media. METHOD: One hundred and forty three patients with chronic otitis media were treated by canal wall-down tympanoplasty with ossiculoplasty in a single stage. According to material of prosthesis, they were classified as titanium group (group A, 52 cases), hydroxypatite group (group B, 47 cases) and autogenous bone group(group C, 44 cases). The postoperative complication and hearing thresholds were analyzed in the 24 months follow-up. Average postoperative air-conduction gain and air-bone gap were measured at four frequencies: 0.5, 1.0.2, and 4.0 kHz. RESULT: 12-month after operation, the average air threshold and air-bone gaps of the three groups were reduced (P < 0.05). The reconstruction successful rate (78.7%) of group A was slightly better than that of B, C (68.1%, 70.4%), there was no statistically significant difference. The difference of the average air threshold and air-bone gaps of group B, C after 24-month of operation and 12-month after operation was statistically significant (P < 0.05). The reconstruction successful rate (48.9%, 45.5%) of group B, C was lower than that of A (76.9%), the difference was also statistically significant (P < 0.05). CONCLUSION: Prostheses using titanium type could give good functional results and strong stability with low complication.

Taurine detected using high-resolution magic angle spinning (1)H nuclear magnetic resonance: A potential indicator of early myocardial infarction.

Magnetic resonance spectroscopy (MRS) is a unique non-invasive method for detecting cardiac metabolic changes. However, MRS in cardiac diagnosis is limited due to insensitivity and low efficiency. Taurine (Tau) is the most abundant free amino acid in the myocardium. We hypothesized that Tau levels may indicate myocardial ischemia and early infarction. Sprague-Dawley rats were divided into seven groups according to different time points during the course of myocardial ischemia, which was induced by left anterior descending coronary artery ligation. Infarcted myocardial tissue was obtained for high-resolution magic angle spinning (1)H nuclear magnetic resonance (NMR) analysis. Results were validated via high-performance liquid chromatography. The Tau levels in the ischemic myocardial tissue were reduced significantly within 5 min compared with those in the control group (relative ratio from 20.27±6.48 to 8.81±0.04, P<0.05) and were maintained for 6 h post-ischemia. Tau levels declined more markedly (56.5%) than creatine levels (48.5%) at 5 min after ligation. This suggests that Tau may have potential as an indicator in the early detection of myocardial ischemia by (1)H MRS.

The correlation between carotid-femoral pulse wave velocity and composition of the aortic media in CAD patients with or without hypertension.

OBJECTIVES: To investigate the influence of hypertension on large artery elasticity and the microstructure of the ascending aortic media in patients with coronary artery disease (CAD), and the association between arterial compliance and composition of the ascending aorta. METHODS: 60 patients with CAD who underwent coronary artery bypass graft surgery were divided into two groups: 30 patients in a hypertension group and 30 patients in a non-hypertension group. Carotid-femoral pulse wave velocity (cfPWV) was measured by an automatic device (Complior, Artech, France). The severity of coronary atherosclerosis was assessed after selective coronary angiography using the Gensini score system. A quantitative study was conducted on ascending aorta specimens by histological and computer image analysis. RESULTS: cfPWV of the hypertension group was higher than that of the non-hypertension group. The relative content of collagen in the ascending aortic media of the hypertension group was higher than that of the non-hypertension group, while the relative content of elastin in the ascending aortic media of the hypertension group was lower than that of the non-hypertension group. cfPWV showed a positive correlation with relative contents of collagen in the ascending aorta and a negative correlation with relative contents of elastin in the ascending aorta in the two groups. CONCLUSIONS: Hypertension may raise the contents of collagen and decrease the contents of elastin in the ascending aortic media of patients with CAD, which in turn may decrease the patients' large artery compliance. cfPWV may reflect the quantitative changes of collagen and elastin in the ascending aortic media in CAD patients independently of hypertension.

Cardiac functional improvement in rats with myocardial infarction by up-regulating cardiac myosin light chain kinase with neuregulin.

AIMS: Recombinant human neuregulin-1 (rhNRG-1) improves cardiac function in experimental heart failure models, but the underlying mechanism remains largely unknown. In this study, we evaluated whether rhNRG-1 could improve cardiac function via the cardiac myosin light chain kinase/myosin light chain 2 ventricular (cMLCK/MLC-2v) pathway in rats with myocardial infarction (MI). METHODS AND RESULTS: Rats with MI were intravenously infused with rhNRG-1 (5 µg/kg/h) for 7 days through osmotic pumps. The mechanism of action of rhNRG-1 was investigated by assaying the non-infarcted myocardium with gene chips. The cMLCK expression, phosphorylated MLC-2v and cardiac function were significantly up-regulated, as assessed by real-time PCR, Western blot and echocardiography, in those animals treated with rhNRG-1. Moreover, the restoration of rhNRG-1-induced sarcomeric organization in serum-free cultured neonatal rat cardiomyocytes with rhNRG-1 was inhibited by cMLCK RNA interference or ML-7, an inhibitor of MLCKs. Adenovirus containing the rat cMLCK coding region was injected into non-infarcted myocardium, and cardiac function was monitored using echocardiography and a haemodynamic machine. The dP/dt and fractional shortening decreasing significantly after MI, and improved by 15.7 and 32.1%, respectively, following local cMLCK application (all P < 0.05). CONCLUSION: Our results suggest that cMLCK is a downstream effector of rhNRG-1 involved in rhNRG-1-induced cardiac function improvement, and that myocardial cMLCK up-regulation can improve cardiac function in rats with MI.