Fractional Shortening Research Articles

Polyethylene glycol loxenatide protects diabetic kidneys by inhibiting GRP78/PERK/eIF2α pathway, and improves cardiac injury by suppressing TLR4/NF-κB inflammatory pathway

BackgroundCardiovascular and renal complications of type 2 diabetes are the main causes of death in diabetic patients. Clinical studies have found that polyethylene glycol loxenatide (PEG-Loxe), a GLP-1 analog widely used to treat type 2 diabetes, boosts renal and cardiac functions in diabetic patients. However, its mechanism of action remains to be elucidated.MethodsUsing injury models of HK-2 human renal proximal tubular epithelial cells and H9C2 rat myocardial cells, as well as db/db mouse models of type 2 diabetes, this study assessed the protective effects of PEG-Loxe on T2DM mice kidneys and hearts and revealed their mechanisms of action.ResultsPEG-Loxe treatment significantly reduced the contents of serum creatinine, urea nitrogen, and 24 h urine protein, alleviated glomerular injury and inflammatory reaction, markedly elevated cardiac left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) levels, diminished pathological injuries in cardiac tissues, and improved renal and cardiac functions in db/db mice. In addition, PEG-Loxe considerably decreased the GRP78 mRNA and protein expressions of GRP78, p-eIF2α, ATF4, and CHOP in the kidneys of T2DM mice, inhibited GRP78/PERK/eIF2α pathway-related proteins in HK-2 cells cultured in high glucose concentrations, subdued renal endoplasmic reticulum stress, and eased renal injury in T2DM mice. PEG-Loxe also obstructed the TLR4/NF-κB inflammatory pathway and myocardial apoptosis and mitigated cardiac trauma in T2DM by reducing TLR4, MyD88, and p-NF-κBp65 protein expressions in cardiac tissues. The H9C2 cell experiment further confirmed PEG-Loxe’s ability to protect the cardiovascular system of T2DM patients by inhibiting the TLR4/NF-κB inflammatory pathway and lessening LDH and CK-MB levels.ConclusionWe showed that PEG-Loxe could decrease renal stress response and improve renal injury in T2DM by inhibiting endoplasmic reticulum stress via the GRP78/PERK/eIF2α pathway. Additionally, PEG-Loxe could hinder the TLR4/NF-κB inflammatory pathway and myocardial apoptosis and boost cardiac function, thus exerting protective effects on the cardiovascular system in T2DM.

Impact of electronic cigarette vaping on the cardiovascular function in young and old rats

BackgroundWhile the acute exposure to electronic cigarette (E-cig) vapor has been associated with an increase in blood pressure, the chronic effect of E-cig vapor on blood pressure compared to standard cigarette smoke has not been extensively studied. We determined the effect of E-cig exposure on blood pressure and other measures of cardiac function in both young and old rats.MethodsYoung Sprague Dawley rats (6 weeks old, both sexes) were randomly exposed to air (n = 34), E-cig with nicotine (E-cig Nic+; n = 30), E-cig without nicotine (E-cig Nic-; n = 28) or standard cigarette smoke (n = 27). Old Fischer 344 rats (25 months old, both sexes) were randomized into 2 groups: (1) 26 rats in the purified air (negative control) group and (2) 17 rats in the electronic cigarette vapor plus nicotine group (E-cig Nic+). After 12 weeks of exposure, hemodynamics were determined by Millar catheter, echocardiography, and thermodilution catheter, a few days after their last exposure.ResultsIn young rats, cigarette smoke was associated with higher systolic, diastolic and mean blood pressures and peak LV systolic pressure, compared to air or E-cig Nic + or E-cig Nic- groups. Neither fractional shortening nor cardiac output differed among the groups. Absolute value for dp/dt min, a measure of diastolic LV function, was lowest in the E-cig Nic- group. Tau, a measure of LV relaxation was worse in this group as well. In old rats, E-cig vaping did not change heart rate, blood pressure, and cardiac function. However, E-cig Nic + exposure was associated with a greater heart weight/BW and LV weight/BW compared to air exposure in old rats.ConclusionsChronic exposure to E-cig vaping did not cause an increase in blood pressure or heart rate, nor did it change cardiac function compared to air in young rats after 12 weeks of exposure, while standard cigarette smoking was associated with an increase in blood pressure. E-cig vaping was associated with a greater heart weight/BW and LV weight/BW compared to air exposure in old rats, suggested that older animals might be more vulnerable to E-cig stimulus than younger ones.

Clinical significance of myocardial deformation of a left ventricle in children with hypertrophic cardiomyopathy

Purpose: to evaluate the clinical significance of left ventricular myocardial deformation indicators, their relationship with the degree of heart failure and left ventricular hypertrophy in children with hypertrophic cardiomyopathy (HCM). Materials and methods. 61 patients with primary genetically confirmed asymmetric HCM aged 7 to 17 years underwent a comprehensive clinical and echocardiography. Echocardiography determined indicators of left ventricular systolic function: ejection and shortening fractions, global longitudinal, circular and radial myocardial deformations and deformations rates. The assessment of myocardial hypertrophy of left ventricular segments was performed taking into account absolute values in systole and diastole depending on age, recalculated per standard deviation units in the population (Z-score factor). Results. A more pronounced degree of heart failure, a decrease in ejection and shortening fractions, and indicators of left ventricular myocardial deformation were established in all children with non-obstructive and obstructive forms of HCM and an extreme degree of myocardial hypertrophy, in contrast to the non-obstructive form of the disease with a less pronounced degree of hypertrophy. An earlier decrease in myocardial deformation indices was revealed in comparison with ejection and shortening fractions, longitudinal deformation and its speed in comparison with radial and circular, their speeds. Conclusions. 1. In children with HCM and extreme degrees of left ventricular myocardial hypertrophy, compared with mild and moderate hypertrophy, a more pronounced degree of heart failure is observed, which is accompanied by a decrease in left ventricular systolic function. Among them, a decrease in myocardial deformation rates and their velocities is more sensitive compared to left ventricular ejection fractions and shortening. 2. Reduction of left ventricular myocardial deformation in children with HCM depends on the degree of hypertrophy. The earliest, manifesting itself even with a mild degree of hypertrophy, is a decrease in longitudinal deformation and its speed compared to circular and radial deformations and their speeds. 3. Determining the indicators of left ventricular myocardial deformation in children with HCM in comparison with the degree of myocardial hypertrophy is of great clinical importance in assessing the systolic function of the left ventricle to optimize administration tactics and timely treatment of the disease.

The Role of NAD+ in Myocardial Ischemia-induced Heart Failure in Sprague-dawley Rats and Beagles.

Nicotinamide adenine dinucleotide (NAD+) participates in various processes that are dysregulated in cardiovascular diseases. Supplementation with NAD+ may be cardioprotective. However, whether the protective effect exerted by NAD+ in heart failure (HF) is more effective before acute myocardial infarction (MI) or after remains unclear. The left anterior descending arteries of male Sprague Dawley rats and beagles that developed HF following MI were ligated for 1 week, following which the animals were treated for 4 weeks with low, medium, and high doses of NAD+ and LCZ696. Cardiac function, hemodynamics, and biomarkers were evaluated during the treatment period. Heart weight, myocardial fibrosis, and MI rate were measured eventually. Compared with the HF groups, groups treated with LCZ696 and different doses of NAD+ showed increased ejection fractions, fractional shortening, cardiac output, and stroke volume and decreased end-systolic volume, end-systolic dimension, creatine kinase, and lactic dehydrogenase. LV blood pressure was lower in the HF group than in the control group, but this decrease was significantly greater in the medium and high NAD+ dose groups. The ratios of heart weight indexes, fibrotic areas, and MI rates in the CZ696 and medium and high NAD+ dose groups were lower than those in the HF group. Medium and highdose NAD+ showed superior positive effects on myocardial hypertrophy, cardiac function, and myocardial fibrosis and reduced the MI rate.

Cardiovascular profile score (CVPS) and selected cardiac parameters in fetuses with Vein of Galen Malformation.

Vein of Galen Malformation (VGAM) is a rare congenital cerebrovascular anomaly. Early detection and monitoring of concurrent fetal heart failure in VGAM are crucial for improving outcomes. The study aims to evaluate heart anatomy, systolic and diastolic heart function, and indicators of heart failure in fetuses referred to a tertiary center due to VGAM detected in the second or third trimester. This single-center retrospective study of echocardiographic data from five fetuses with VGAM examined between 2008 and 2023. Parameters analyzed included gestational age, reason for referral, cardiovascular profile score (CVPS), systolic and diastolic heart function and selected cardiac parameters RESULTS: Cardiomegaly as a sign of congestive heart failure was the main reason for referral most of the fetuses (4/5 - 80%) diagnosed later as VGAM in our center. Abnormal cerebral vessel flow was visualized in all cases, with normal umbilical arterial flow. Three fetuses were treated prenatally with digoxin due to congestive heart failure. Monophasic tricuspid valve inflow and decreased shortening fraction (SF) were observed in three fetuses (60%) at the time of diagnosis. CVPS scores ranged from 2 to 10, correlating with the severity of cardiac compromise. All five patients demised, three died in utero, and two shortly after birth. This study emphasizes the severe cardiac implications of VGAM detected in utero and the need for early and comprehensive fetal assessment. Despite early diagnosis, outcomes remain poor, necessitating further research into effective prenatal treatments and management protocols to enhance survival for affected fetuses.

Mechanism of jianxin granules in the treatment of heart failure based on proteomics and metabolomics

BackgroundHeart failure (HF) is associated with high mortality and rehospitalization rates, highlighting the need for novel therapeutic approaches. Jianxin (JX) granules, a Traditional Chinese Medicine formulation, have been patented for the treatment of HF. However, the specific therapeutic effects and underlying mechanisms of JX granules have not been fully elucidated. This study aimed at investigating the effects and mechanism of JX granules in the treatment of HF based on proteomics and metabolomic profiling.MethodsHF model was established in rats by ligation of left coronary artery. The successfully modeled rats were randomly divided into three groups: the model group, the JX granules group, and Sacubitril/Valsartan (S/V) group. Four weeks after treatment, left ventricular (LV) function was evaluated via echocardiography. LV fibrosis and apoptosis were examined through histological analyses, while mitochondrial morphology was assessed using transmission electron microscopy. Quantitative assessment of oxidative stress was also conducted. Proteomics was used to identify the differentially expressed proteins and potential pathways. Metabolomics was utilized to elucidate the variations in metabolism. Then western blotting and in vitro analyses were performed.ResultsA rat model of HF was established, evidenced by a decrease in left ventricular ejection fraction (LVEF), stroke volume (SV), and left ventricular fractional shortening (LVFS), alongside diminished adenosine triphosphate (ATP) content, elevated oxidative stress, augmented apoptosis, and disrupted pyruvate metabolism. Treatment with JX granules ameliorated these effects, improving systolic function, reducing ventricular chamber size, and increasing LVEF, SV, and LVFS, as assessed by echocardiography. Additionally, JX granules attenuated cardiac fibrosis and improved mitochondrial structure, as evidenced by less vacuolation and clearer mitochondrial cristae, when compared to the model group. The treatment also regulated apoptosis-related protein expression, partially reversing the increase in cleaved Caspase-9, cleaved Caspase-3, and Bax and the suppression of Bcl-2 observed in the heart failure rats. All of these effects were similar to S/V. Proteomic and metabolomic analyses identified key differential genes, such as triosephosphate isomerase 1 (TPI1), lactate dehydrogenase B (LDHB), pyruvate kinase M (PKM), protein kinase B (Akt), Pyruvate Dehydrogenase Beta (PDHB) and lactate dehydrogenase A (LDHA), as well as vital pathways including carbon metabolism, the PI3K-Akt signaling pathway, pyruvate metabolism, and HIF-1α signaling pathway. Moreover, JX granules mitigated oxidative stress, inhibited apoptosis, and activated Akt in H9c2 cells exposed to angiotensin II, which could be reversed by the PI3K inhibitor LY294002.ConclusionJX granules improve HF in parallel to the efficacy of S/V, at least in part, through enhancing pyruvate metabolism, inhibiting oxidative stress and activating PI3K/Akt pathway.

Endothelial FOSL1 drives angiotensin II-induced myocardial injury via AT1R-upregulated MYH9.

Vascular remodeling represents a pathological basis for myocardial pathologies, including myocardial hypertrophy and myocardial infarction, which can ultimately lead to heart failure. The molecular mechanism of angiotensin II (Ang II)-induced vascular remodeling following myocardial infarction reperfusion is complex and not yet fully understood. In this study, we examined the effect of Ang II infusion on cardiac vascular remodeling in mice. Single-cell sequencing showed Ang IIinduced cytoskeletal pathway enrichment and that FOS like-1 (FOSL1) affected mouse cardiac endothelial dysfunction by pseudotime analysis. Myosin heavy chain 9 (MYH9) was predominantly expressed in primary cardiac endothelial cells. The Ang II type I receptor blocker telmisartan and the protein kinase C inhibitor staurosporine suppressed Ang II-induced upregulation of MYH9 and FOSL1 phosphorylation in human umbilical vein endothelial cells. Silencing MYH9 abolished Ang II-mediated inhibition of angiogenesis in human umbilical vein endothelial cells, and attenuated AngII-induced vascular hyperpermeability. We found that FOSL1 directly bound to the MYH9 promoter and thus activated transcription of MYH9 by the dual luciferase reporter and chromatin immunoprecipitation assays, leading to vascular dysfunction. In vivo, 6 weeks after injecting adeno-associated virus-ENT carrying the TEK tyrosine kinase (tie) promoter-driven short hairpin RNA for silencing FOSL1 (AAV-tie-shFOSL1), cardiac function represented by the ejection fraction and fractional shortening was improved, myocardial fibrosis was decreased, protein levels of phosphorylated FOSL1, MYH9, and collagen type I alpha were reduced, and cardiac vascular density was recovered in mice with endothelial Fosl1-specific knockdown in Ang II-infused mice. In ischemia-reperfusion mice, AAV-shFosl1 mice had a reduced infarct size and preserved cardiac function compared with control AAV mice. Our findings suggest a critical role of the FOSL1/MYH9 axis in hindering Ang II-induced vascular remodeling, and we identified FOSL1 as a potential therapeutic target in endothelial cell injuries induced by myocardial ischemia-reperfusion.

Vanillic acid attenuates doxorubicin-induced cardiotoxicity by regulating PINK1/Parkin/Mfn2 signaling pathway

ObjectivesThe aim of this study was to explore the potential protective effects of vanillic acid (VA) against doxorubicin (DOX)-induced cardiotoxicity and unravel the underlying molecular mechanisms involved. MethodsThe DOX -induced myocardial toxicity model was established in Sprague-Dawley (SD) rats by intraperitoneal injection of doxorubicin. Simultaneously, different concentrations of VA were administered for intervention. After modeling, rat cardiac function was evaluated using an ultrasound machine. The detection of creatine kinase isoenzyme MB (CK-MB) levels in rat serum using a biochemical analyzer. HE staining method was used to observe myocardial pathological changes, Masson's trichrome staining was performed to assess the degree of myocardial fibrosis. The observation of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) levels in myocardial tissue using assay kits. Western blotting and immunohistochemistry was conducted to detect protein expression levels of PINK1, Parkin, P62, LC3I/II, Mfn2, Drp1, OPA, and Fis1. ResultsCompared to the DOX group, intervention with VA demonstrates ameliorative effects on doxorubicin-induced cardiotoxicity, as evidenced by improvements in left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), and a reduction in left ventricular end-diastolic diameter (LVEDd) in rats. Additionally, the application of VA reduced the levels of CK-MB in rat serum. However, there were no statistically significant differences observed in heart rate. Histological examination reveals that VA administration positively impacts the arrangement of myocardial fibers and mitigates myocardial fibrosis in the rat hearts subjected to doxorubicin-induced injury. Moreover, relative to the DOX group, the use of VA alleviates DOX-induced myocardial cell apoptosis. VA treatment also upregulates the expression levels of PINK1 and Parkin, leading to the activation of mitochondrial autophagy. Furthermore, VA enhances the expression levels of mitochondrial dynamics proteins Mfn2, Drp1, and Fis1 while downregulating the expression of OPA. Among them, the high-dose group of VA (60 mg/kg·d) showed the most pronounced improvement in DOX-induced cardiotoxicity. ConclusionVA attenuated DOX-induced myocardial injury by up regulating the PINK1/Parkin/Mfn2 signaling pathway.

Andrographolide Attenuates Myocardial Ischemia-Reperfusion Injury in Mice by Up-Regulating PPAR-α.

Andrographolide (AGP), a bioactive diterpene lactone, is an active constituent extracted from Andrographis paniculata. It has many biological activities, such as antioxidant, antitumor, antivirus, anti-inflammation, hepatoprotection, and cardioprotection. The aim of the present study is to investigate the cardioprotective effects of AGP in a mouse model of myocardial ischemia-reperfusion injury (MIRI). Adult male C57BL/6J mice were pre-treated orally with AGP (25mg/kg) for six days. After 30min of the left anterior descending coronary artery occlusion followed by 24h of reperfusion, mice received an additional dose of AGP. The results showed that: (i) AGP pretreatment significantly reduced myocardial infarct size and cardiac injury biomarkers in MIRI mice and improved left ventricular ejection fraction (EF) and fractional shortening (FS); (ii) AGP pretreatment attenuated MIRI-induced oxidative stress imbalance in MIRI mice by increasing total antioxidant capacity (T-AOC) and reducing the levels of hydrogen peroxide (H2O2), nitric oxide (NO), malondialdehyde (MDA), and dihydroethidium (DHE); (iii) AGP pretreatment increased Bcl-2 expression and decreased caspase-3 and Bax expression in ischemic myocardial tissue, along with a reduction in TUNEL-positive cells. Further analysis showed that stimulation by I/R decreased peroxisome proliferator-activated receptor-α (PPAR-α) expression in ischemic cardiac tissue, which was prevented by AGP administration. Moreover, administration of the PPAR-α antagonist GW6471 (1mg/kg) abolished the protective effect of AGP on oxidative stress and apoptosis in the ischemic heart tissue of mice stimulated by ischemia-reperfusion. Taken together, these results suggest that AGP attenuates MIRI-induced cardiac injury by up-regulating PPAR-α expression, thereby preventing oxidative stress and cellular apoptosis.

3D in vitro modelling of post-partum cardiovascular health reveals unique characteristics and signatures following hypertensive disorders in pregnancy

BackgroundHypertensive disorders of pregnancy (HDP) affect 2–8% of pregnancies and are associated postpartum with increased cardiovascular disease (CVD) risk, although mechanisms are poorly understood.MethodsHuman induced pluripotent stem cells (iPSC)-derived cardiomyocytes, cardiac fibroblasts and coronary artery endothelial cells were cocultured to form cardiac spheroids (CSs) in collagen type-1 hydrogels containing 10% patient plasma collected five years postpartum [n = 5 per group: normotensive control, gestational hypertension (GH) and preeclampsia (PE)]. Plasma-treated CSs were assessed for cell viability and contractile function and subjected to immunofluorescence staining and imaging. A quantitative proteomic analysis of plasma samples was conducted (controls n = 21; GH n = 5; PE n = 12).ResultsContraction frequency (CF) was increased in PE-treated CSs (CF: 45.5 ± 3.4 contractions/minute, p < 0.001) and GH-treated CSs (CF: 45.7 ± 4.0 contractions/minute, p < 0.001), compared to controls (CF = 21.8 ± 2.6 contractions/min). Only PE-treated CSs presented significantly increased fractional shortening (FS) % (9.95 ± 1.8%, p < 0.05) compared to controls (3.7 ± 1.1%). GH-treated CSs showed a reduction in cell viability (p < 0.05) and an increase in α-SMA expression (p < 0.05). Proteomics analyses identified twenty differentially abundant proteins, with hemoglobin A2 being the only protein perturbed in both GH and PE versus control plasma (p < 0.05).ConclusionsThe innovative patient-relevant CS platforms led to the discovery of biomarkers/targets linked to cell death signaling and cardiac remodeling in GH-induced CVD and vascular/endothelial cell dysfunction in PE-induced CVD.

Cardiac structural, functional and energetic assessments during and after pregnancy in women with gestational diabetes mellitus, preeclampsia and healthy pregnancy

GDM and preeclampsia are common complications of pregnancy, for which overweight/obesity is a common risk factor. Both conditions are associated with a two-to-four-fold increase in future incident heart failure, which may be linked to early maladaptive myocardial changes. To determine maternal myocardial structural, functional, and energetic responses to pregnancies complicated by gestational diabetes mellitus (GDM) or preeclampsia compared to healthy pregnancies (HP) at third-trimester of pregnancy and twelve-months postpartum. Thirty-eight women with HP, 30 GDM, 20 preeclampsia, 10 non-pregnant controls with overweight (Overweight-NC) and 10 with normal-weight were recruited. Cardiovascular magnetic resonance spectroscopy and imaging were used to define myocardial energetics (phosphocreatine: ATP ratio [PCr/ATP]), left ventricular (LV) volumes, mass, and ejection fraction and global longitudinal shortening (GLS). Pregnancy groups underwent repeat scans twelve-months postpartum, nulliparous-controls were assessed once. During third-trimester, compared to HP, women with either GDM or preeclampsia displayed higher BMI, higher LV-mass (HP:90[85,94]g, GDM:103[96,112], Preeclampsia:118[111,125]g; P=0.001), and lower PCr/ATP (HP:2.2[2.1,2.4], GDM:1.9[1.7,2], Preeclampsia:1.9[1.8,2.1];P=0.0004) and GLS (HP:20[18,21]%, GDM:18[17,19]%, Preeclampsia:16[14,17]%;P=0.01). Post-pregnancy, no group saw significant changes in LV-mass, PCr/ATP or GLS. There were no significant differences in LV-mass, PCr/ATP or GLS between the GDM and preeclampsia groups during or post-pregnancy. Moreover, the Overweight-NC showed no significant differences in LV-mass ( 53[43,63])g, PCr/ATP (2.0[1.8,2.2]) or GLS (-19[17,21]%) compared to GDM or preeclampsia groups during or post-pregnancy. Women with GDM or preeclampsia exhibit similar myocardial phenotypes during pregnancy with persistent subclinical alterations in LV mass, energetics and GLS twelve-months postpartum. These myocardial alterations are similar to those detected in Overweight-NC, potentially suggesting the myocardial changes may predominantly be driven by overweight/obesity.

Right ventricular outflow tract fractional shortening: a novel diagnostic parameter for pulmonary hypertension.

Pulmonary hypertension (PH) is a progressive vascular disease characterized by elevated pulmonary arterial pressure and resistance in the pulmonary vascular bed. It is associated with high morbidity and mortality. Although right heart catheterization (RHC) is the gold standard for diagnosis, noninvasive methods, such as echocardiography, are essential for early detection and management. This study aimed to elucidate the potential of right ventricular outflow tract fractional shortening (RVOT-FS) as a noninvasive diagnostic tool for PH. This single-center observational cohort study was conducted between November 2023 and May 2024. The study included 141 patients referred to the PH clinic (75 with confirmed PH and 66 controls). Echocardiographic measurements were performed using standard protocols, and RVOT-FS was calculated. Hemodynamic parameters were obtained via RHC. RVOT-FS was significantly lower in the PH group (35.71%, IQR: 27.15-43.33) than in the control group (54.50%, IQR: 45.21-69.17) (p < 0.001). RVOT-FS showed negative correlations with mean pulmonary artery pressure (mPAP) (r = -0.664, p < 0.001), pulmonary vascular resistance (PVR) (r = -0.526, p < 0.001), and other RHC and RV echocardiographic parameters. ROC analysis demonstrated that RVOT-FS is a reliable parameter for predicting PH, with an area under the curve (AUC) of 0.866. An RVOT-FS value of 44.05% had a sensitivity of 82.7% and specificity of 83.3% for diagnosing PH. This study revealed that RVOT-FS was significantly lower in the PH group than in the control group. The correlations also observed between RVOT-FS and mPAP, PVR, and other RHC and echocardiographic parameters imply its potential clinical utility.

Ershen Zhenwu Decoction Suppresses Myocardial Fibrosis of Chronic Heart Failure with Heart–Kidney Yang Deficiency by Down-Regulating the Ras Homolog Gene Family Member A/Rho-Associated Coiled-Coil Kinases Signaling Pathway

Ethnopharmacological significanceThe therapeutic efficacy of Ershen Zhenwu Decoction (ESZWD)—a famous formulation from Xin’an for patients with chronic heart failure heart–kidney Yang deficiency (CHF-HKYD)—is well established. Still, the underlying molecular mechanism is not clear. Aim of the studyThis study investigated mechanisms by which ESZWD suppresses cardiac pathology, including myocardial fibrosis, in CHF-HKYD model rats and Ang II-stimulated cardiac fibroblasts (CFs). Materials and methodsThe components in ESZWD were analyzed by ultra-high-performance liquid chromatography coupled with Quadrupole Time-Of-Flight mass spectrometry (UHPLC-Q-TOF-MS). CHF-HKYD model was established in the male Sprague–Dawley rats through bilateral thyroidectomy and intraperitoneal administration of 0.02% doxorubicin (DOX), twice weekly for 3 weeks. Subsequently, the CHF-HKYD model rats were randomly categorized into the Model, ESZWD-L (3.96 g/kg/d ESZWD), ESZWD-M (7.92 g/kg/d ESZWD), ESZWD-H (15.84 g/kg/d ESZWD), and Sac/Val (68 mg/kg/d sacubitril/valsartan) groups and treated daily for 4 weeks. As a control, the sham surgery group (Sham) was used. Primary cardiac fibroblasts (CFs) were categorized into Control, Model, ESZWD, and Sac/Val groups. Then, the CFs were stimulated with Ang-II. The ESZWD and Sac/Val groups were incubated with different concentrations of drug-containing sera and their effects on CF viability were assessed via the CCK-8 assay. The ESZWD and Sac/Val groups received drug-containing serum concentrations determined by CCK-8 assay results. The cardioprotective effects of ESZWD were determined using echocardiography, Hematoxylin & Eosin (H&E) staining, Masson staining, and Sirius red staining, and the Enzyme Linked Immunosorbent Assay (ELISA). ESZWD's effects on the Ras Homolog Gene Family Member A (RhoA) / Rho-Associated Coiled-Coil Kinases (ROCKs) signaling pathway and myocardial fibrosis were assessed by Western blotting and Quantitative Real-Time PCR (qRT-PCR) analyses. Immunofluorescence was used to observe fibrotic markers in CFs. ResultsESZWD treatment improved cardiac function in the CHF-HKYD rats by significantly reducing myocardial fibrosis and ventricular remodeling. ESZWD treatment increased the rats' body temperature (Tb) and 24-hour urine volume, left ventricular ejection fraction (LVEF) and LV fractional shortening (LVFS), and decreased LV internal systolic diameter (LVIDs), LV internal diastolic diameter (LVIDd), and heart weight/ body weight (HW/BW) compared to the Model group. In comparison to the model rats, ESZWD treatment decreased serum levels of B-type natriuretic peptide precursor (NT-proBNP), tumor necrosis factor-alpha (TNF-α), interleukin-11 (IL-11), and IL-17A. ESZWD treatment significantly down-regulated the protein and mRNA expression levels of collagen I A1, α-SMA, RhoA, ROCK1, and ROCK2 in the heart tissues of the CHF-HKYD rats and the Ang II-stimulated CFs. ConclusionESZWD significantly improved cardiac function and attenuated myocardial fibrosis and inflammation in the CHF-HKYD rats by inhibiting the RhoA/ROCKs signaling pathway.

Cross-sectional Study of the Association between Plasma Brain Natriuretic Peptide Levels and Left Ventricular Shortening Fraction in Fukuyama Congenital Muscular Dystrophy.

Cross-sectional Study of the Association between Plasma Brain Natriuretic Peptide Levels and Left Ventricular Shortening Fraction in Fukuyama Congenital Muscular Dystrophy.

Male Wistar Rats Chronically Fed with a High-Fat Diet Develop Inflammatory and Ionic Transport Angiotensin-(3-4)-Sensitive Myocardial Lesions but Preserve Echocardiographic Parameters.

The central aim of this study was to investigate whether male Wistar rats chronically fed a high-fat diet (HFD) over 106 days present high levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and Na+ and Ca2+ transport alterations in the left ventricle, together with dyslipidemia and decreased glucose tolerance, and to investigate the influence of Ang-(3-4). The rats became moderately overweight with an expansion of visceral adiposity. Na+-transporting ATPases, sarco-endoplasmic reticulum Ca2+-ATPase (SERCA2a), and the abundance of Angiotensin II receptors were studied together with lipid and glycemic profiles from plasma and left-ventricle echocardiographic parameters fractional shortening (FS) and ejection fraction (EF). IL-6 and TNF-α increased (62% and 53%, respectively), but returned to normal levels with Angiotensin-(3-4) administration after 106 days. Significant lipidogram alterations accompanied a decrease in glucose tolerance. Angiotensin II receptors abundance did not change. (Na+ + K+)ATPase and ouabain-resistant Na+-ATPase were downregulated and upregulated, respectively, but returned to normal values upon Angiotensin-(3-4) administration. SERCA2a lost its ability to respond to excess ATP. Echocardiography showed no changes in FS or EF. We conclude that being overweight causes an increase in Ang-(3-4)-sensitive IL-6 and TNF-α levels, and ion transport alterations in the left ventricle that could evolve into future heart dysfunction.

Peripheral microvessel area better predicts the severity of coronary stenosis of acute myocardial infarction patients over pulse wave velocity

Microvascular obstruction (MVO) is linked with adverse clinical outcome in acute coronary syndrome (ACS) patients, therefore, early prediction of MVO with non-invasive peripheral microcirculation is crucial in facilitating optimal treatment. Current study aims to analyze the significance of opisthenar microvessel area (OMA, measured using optical coherence tomography, OCT) in predicting coronary stenosis (Gensini score, GS) and short-term cardiac recovery of ACS patients and the results were compared to those of arterial stiffness parameters (Pulse Wave Velocity, PWV; Ankle-Brachial Index; ABI). Results showed that cardiac functional parameters (e.g. ejection fraction, EF; fractional shortening, FS) and OMA were higher in normal/low risk (GS 0–≤ 20, n = 69) compared to medium/high risk patients (GS > 20, n = 44, P < 0.0001). Furthermore, OMA, EF or FS was negatively associated with the severity of coronary stenosis (P < 0.0001). In addition, OMA was negatively correlated with heart and liver damage parameters (e.g. creatine kinase, CK; creatine kinase muscle brain, CKmB; lactate dehydrogenase, LDH; hydroxybutyrate dehydrogenase, HDBH; aspartate aminotransferase, AST; alanine aminotransferase, ALT) or with inflammatory markers (neutrophil, neutrophil/lymphocyte ratio, NEU, NEU/LYM (NLR); systemic immune inflammation index, SII and system inflammation response index, SIRI), indicating clinical significance of OMA. Conversely, PWV and ABI were not associated with coronary stenosis or organ damage markers. Receiver Operator Characteristic (ROC) analysis showed high specificity and sensitivity of OMA for coronary stenosis (specificity 0.864 or sensitivity 0.87). In conclusion, OMA shows negative associations with the severity of coronary stenosis and adverse clinical parameters indicate that microcirculation measurement from opisthenar possesses prognostic value for severe ACS patients.

Evaluation of fetal heart size, morphology and function with fetal growth restriction using fetal HQ

BackgroundFetal growth restriction (FGR) is associated with various perinatal complications. Limited research has focused on the fetal heart in the context of FGR. This study aimed to investigate the application value of fetal heart quantification (HQ) technology in evaluating the size, morphology, and function of the heart in FGR.MethodsA total of 31 fetuses diagnosed with FGR in our hospital from April 2022 to May 2024 were included, alongside another 31 normal fetuses matched for gestational age as the control group. Ultrasound Doppler parameters of the middle cerebral artery (MCA), umbilical artery (UA), venous catheter, and fetal HQ parameters were collected for comparative analysis, and perinatal data were followed up.ResultsFetuses with FGR exhibited significant differences in various parameters of the MCA and UA compared to the control group (P < 0.05). The four-chamber view end-diastolic transverse width, end-diastolic area, left ventricular (LV) end-diastolic area, end-systolic area, end-systolic length, end-diastolic volume, end-systolic volume, and right ventricular (RV) end-systolic area in the FGR group were significantly lower than those in the control group (P < 0.05). In the 24-segment analysis, the LV fractional shortening in the FGR group was greater than in the control group at segments 12 to 14, while the end-diastolic diameter (ED) at segments 5 to 13 of the LV and segments 1 to 14 of the RV were smaller than those in the control group, with statistical significance (P < 0.05). Analysis of each subgroup indicated that fractional shortening (FS) in the early-onset group was significantly greater than in the late-onset group at RV segments 2 to 8. LV-ED at segments 1 to 15 and RV-ED at segments 1 to 16 were significantly smaller in the early-onset group than in the control group, and LV ED segments 20 to 21 were significantly smaller in the early-onset group compared to the late-onset group (P < 0.05). FS in the mild group was significantly larger than in the normal group at LV segments 10 to 16. The severe group exhibited significantly smaller LV segment 2 to 11 ED and the mild group showed smaller RV segments 1 to 13 compared to the control group (P < 0.05).ConclusionsFetal HQ is a promising technique for evaluating the cardiac function, size, and morphology in cases of FGR.

Relative Factor Analysis of Postoperative Complications in Infants Below 1 Year Undergoing Repair of Ventricular Septal Defect Combined with Other Procedures through a Right Axillary Incision

Background: Compared to the traditional surgical repair of isolated ventricular septal defects, the proportion of complex congenital heart diseases has been increasing due to advancements in diagnostic capabilities and surgical techniques. Concomitant surgeries to correct multiple congenital heart diseases have become the preferred choice. Therefore, the evaluation of the safety of the combined correction of ventricular septal defects with other cardiac anomalies in young children through a right axillary incision and the analysis of related factors of perioperative complications needs to be investigated. Methods: A retrospective study was conducted on a single-center patient sample from January 2018 to December 2022 to compare outcomes between infants undergoing isolated ventricular septal defect (VSD) repair via a right axillary thoracotomy (control group) and those undergoing VSD repair combined with other cardiac procedures (experimental group). Results: A total of 397 eligible infants were included. After baseline data were matched using propensity score matching, the experimental group (n = 181) and the control group (n = 107) showed no significant differences in intraoperative blood loss, postoperative total drainage, length of hospital stay, duration of ICU monitoring, Vasoactive-Inotropic Score (VIS), pre-discharge left ventricular ejection fraction, fractional shortening (FS), postoperative severe pulmonary infection, reoperation, mortality, postoperative atrioventricular block, chylothorax, cardiac arrest, pericardial effusion, pneumothorax, pulmonary atelectasis, tricuspid regurgitation, myocardial injury, abdominal effusion, and metabolic acidosis. However, the control group had shorter surgical time [28.00 (90.00, 196.00) vs. 140.00 (95.00, 658.00) min, p &lt; 0.05], shorter cardiopulmonary bypass time [58.00 (24.00, 114.00) vs. 66.00 (33.00, 422.00) min, p &lt; 0.05], shorter aortic cross-clamp time [32.00 (17.00, 62.00) vs. 37.00 (15.00, 142.00) min, p &lt; 0.05], and shorter postoperative mechanical ventilation time [22.00 (0, 99.00) vs. 23.00 (3.00, 193.00) h, p &lt; 0.05]. The rate of abdominal effusion was lower in the experimental group than in the control group (p = 0.044). In the analysis of postoperative complication-related factors, the preoperative grade of tricuspid regurgitation, postoperative mechanical ventilation time, and VIS were positively correlated with abdominal effusion and satisfied the variable (p &lt; 0.05) in each of three established models. In the single-factor analysis, both VIS and preoperative lymphocyte count were (p &lt; 0.1) related to pericardial effusion; however, in the multi-factor analysis, only VIS met the threshold (p &lt; 0.05). Gender, height, and VIS were each associated with pleural effusion (p &lt; 0.05). Conclusion: The combination of ventricular septal defect repair with other cardiac procedures via a right axillary thoracotomy did not significantly differ from isolated VSD repair in terms of postoperative complications, monitoring, and length of hospital stay. However, increased surgical complexity was associated with longer surgical and mechanical ventilation times. Factors such as tricuspid regurgitation severity, duration of postoperative mechanical ventilation, and VIS were identified as relative factors for postoperative effusion. Additionally, the risk of postoperative pericardial effusion increased with higher VIS, while gender, height, and VIS were identified as relative factors for postoperative chylothorax.

Downregulation of miR-214 promotes dilated Cardiomyopathy Progression through PDE5A-Mediated cGMP regulation

Dilated cardiomyopathy (DCM) is a myocardial disorder resulting in a substantial decline in cardiac function and potentially leading to heart failure. This research combines bioinformatics analysis with empirical validation to explore the roles and mechanisms of miR-214 in DCM. Using the DEseq2 R package, a total of 125 differentially expressed circulating miRNAs (DE c-miRNAs) and 784 DE genes (DEGs) were identified. Cross-analysis between target genes of DE c-miRNAs and DEGs identified 124 common genes, and protein-protein interaction analysis of common genes identified 11 hub genes. Twelve DE c-miRNAs were further verified by quantifying their levels in the serum of DCM patients and healthy individuals. miR-214 levels were significantly decreased in serum from DCM patients, positively correlated with left ventricular ejection fraction and left ventricular fractional shortening. Further analysis showed that miR-214 directly targets and negatively regulates phosphodiesterase 5 A (PDE5A). Elevated PDE5A expression reduced cGMP levels; however, using sildenafil, a PDE5A inhibitor, reversed this effect, substantiating the regulatory mechanism of miR-214 on cGMP via PDE5A. These results provide new potential targets for the diagnosis and treatment of DCM.

High frequency of occult transthyretin and apolipoprotein AI–type amyloid in aortic valves removed by valve replacement for aortic stenosis

Background A high incidence of valvular involvement of amyloid in the setting of aortic stenosis (AS) has been reported. Amyloid derived from ApoAI (AApoAI) can form local amyloid deposits in the aortic valve. Although a high prevalence of concomitant severe AS and cardiac transthyretin-type amyloidosis (ATTR) has been reported, the prevalence of valvular involvement by ATTR and AApoAI is unclear. Methods Using immunostaining and mass spectrometry, we analysed amyloid proteins in 97 aortic valves removed for valve replacement due to AS at Kyoto Prefectural University of Medicine between 2014 and 2021. Clinical information was also reviewed. Results Amyloid deposits were found in 44 cases (45%), of which 30 cases (68%) involved ATTR and 33 cases (75%) AApoAI. Statistical analysis showed significantly lower age and E/e′ among amyloid-positive cases compared with amyloid-negative cases and significantly lower brain natriuretic peptide, higher fractional shortening, and higher left ventricular ejection fraction among ATTR-positive cases compared with ATTR-negative cases. Seven recent patients underwent bone scintigraphy and ATTR cardiomyopathy was observed in only one case. Conclusions AS symptoms can manifest earlier in patients with amyloid or ATTR deposition in the aortic valve than in patients without such deposition, even though left ventricular function is preserved.