Cardiac Morphological Changes Research Articles

Coronary CTA-based Vascular Radiomics Predicts Atherosclerosis Development Proximal to LAD Myocardial Bridging.

Cardiac cycle morphological changes can accelerate plaque growth proximal to myocardial bridging (MB) in the left anterior descending artery (LAD). To assess coronary CT angiography (CCTA)-based vascular radiomics for predicting proximal plaque development in LAD MB. Patients with repeated CCTA scans showing LAD MB without proximal plaque in index CCTA were included from Jinling Hospital as development set. They were divided into training and internal testing in an 8:2 ratio. Patients from 4 other tertiary hospitals were set as external validation set. The endpoint was proximal plaque development of LAD MB in follow-up CCTA. Four vascular radiomics models were built: MB centerline (MB CL), proximal MB CL (pMB CL), MB cross section (MB CS), and proximal MB CS (pMB CS), whose performances were evaluated using area under the curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI). 295 patients were included in the development (n=192; median age, 54±11 years; 137 men) and external validation sets (n=103; median age, 57±9 years; 57 men). The pMB CS vascular radiomics model exhibited higher AUCs in training, internal test, and external sets (AUC=0.78, 0.75, 0.75) than the clinical and anatomical model (all p<0.05). Integration of the pMB CS vascular radiomics model significantly raised the AUC of the clinical and anatomical model from 0.56 to 0.75 (p=0.002), along with enhanced NRI (0.76 [0.37-1.14], p<0.001) and IDI (0.17 [0.07-0.26], p<0.001) in the external validation set. The CCTA-based pMB CS vascular radiomics model can predict plaque development in LAD MB.

Maternal supplementation with docosahexaenoic acid does not cause constriction of fetal ductus arteriosus: randomized controlled trial.

Docosahexaenoic acid (DHA) is recommended routinely in pregnancy to promote fetal development. DHA has anti-inflammatory activity, but its effects on the fetal heart and circulation are unknown. This study aimed to investigate whether maternal DHA supplementation in the third trimester affects maternal prostaglandin levels and fetal ductus arteriosus flow dynamics. This was a double-blind randomized controlled trial with parallel groups conducted between 2018 and 2021. Pregnant women aged over 18 years with a normal fetus at 27-28 weeks' gestation showing no cardiac/extracardiac anomalies or ductal constriction were eligible for the trial. Women consuming substances with a known inhibitory effect on prostaglandin metabolism, such as non-steroidal anti-inflammatory drugs and polyphenol-rich foods, were excluded. The intervention group received oral supplementation of omega-3 with 450 mg/day of DHA for 8 weeks and the placebo group received capsules of soy lecithin for 8 weeks. Anthropometric measurements, assessment of polyphenol and omega-3 consumption, fetal morphological ultrasound examination, fetal Doppler echocardiographic examination and blood sample collection were performed at the start of the study and the latter two were repeated at follow-up. Prostaglandin E2 (PGE2) level and echocardiographic parameters were compared between the intervention and placebo groups and between baseline and follow-up. A total of 24 participants were included in each group. After 8 weeks, there were no significant differences between the intervention and placebo groups in maternal serum PGE2 level or Doppler echocardiographic parameters of ductal flow. No case of ductus arteriosus constriction was observed. The expected intragroup changes in cardiac morphology, as a result of advancing gestation, were present. Maternal DHA supplementation in the third trimester at a clinically recommended dose did not result in inhibition of PGE2 or constriction of the ductus arteriosus. These findings should be confirmed in postmarket surveillance studies with larger patient numbers in order to test the full safety profile of DHA and provide robust clinical reassurance. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Myocardial Blood Flow in Newly Diagnosed Breast Cancer Patients at Rest and During Exercise

Heart depends critically on continuous supply of blood, but it is unknown whether cancer, without any treatments, affects myocardial blood flow (MBF) at rest or during exercise. This study therefore aimed at measuring MBF in cancer patients and control subjects and it was hypothesized that MBF is affected by cancer. The study included recently-diagnosed breast cancer patients (n=18) who had not started their oncologic treatments and age-matched female control participants (n=32). Controls were women referred to cardiac diagnostic testing but who were by this testing judged to be free of obstructive coronary artery disease. MBF was quantified with [15O]H2O positron emission tomography (PET) at rest in both groups and additionally during 10-min supine bicycling exercise in the breast cancer patients. Furthermore, cardiac morphological changes were analyzed with a breast cancer mice-model four weeks after the inoculation of 13TC mammary tumor cells. Respective mice without tumors served as controls. Resting heart rate (HR) and rate pressure product (RPP) correlated positively with resting MBF, but were similar in both groups resulting also in similar resting MBF in cancer patients and controls. MBF increased significantly from rest during exercise in breast cancer patients (p&lt;0.0001) and exercising MBF correlated positively with the histologic grade of cancer (r=0.54, p=0.021). However, cancer grade did not associate with exercise intensity measures such as HR, RPP or HR percentage from age-predicted maximal HR. In the mouse model, the breast cancer did not affect heart weight, cardiomyocyte size, myocardial capillary density, or capillary-to-myocyte size ratio. In conclusion, resting MBF in humans or myocardial capillarity in mice appear not to be affected by breast cancer. However, the more severe is the histologic grade of cancer, the higher is the MBF during exercise in patients with breast cancer, independently of the intensity of the exercise suggesting dysregulation of myocardial blood supply with cancer. This novel finding requires further investigations. This study was financially supported by Academy of Finland and Hospital District of South-West Finland. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Age-Dependent RGS5 Loss in Pericytes Induces Cardiac Dysfunction and Fibrosis.

Pericytes are capillary-associated mural cells involved in the maintenance and stability of the vascular network. Although aging is one of the main risk factors for cardiovascular disease, the consequences of aging on cardiac pericytes are unknown. In this study, we have combined single-nucleus RNA sequencing and histological analysis to determine the effects of aging on cardiac pericytes. Furthermore, we have conducted in vivo and in vitro analysis of RGS5 (regulator of G-protein signaling 5) loss of function and finally have performed pericytes-fibroblasts coculture studies to understand the effect of RGS5 deletion in pericytes on the neighboring fibroblasts. Aging reduced the pericyte area and capillary coverage in the murine heart. Single-nucleus RNA sequencing analysis further revealed that the expression of Rgs5 was reduced in cardiac pericytes from aged mice. In vivo and in vitro studies showed that the deletion of RGS5 impaired cardiac function, induced fibrosis, and morphological changes in pericytes characterized by a profibrotic gene expression signature and the expression of different ECM (extracellular matrix) components and growth factors, for example, TGFB2 and PDGFB. Indeed, culturing fibroblasts with the supernatant of RGS5-deficient pericytes induced their activation as evidenced by the increased expression of αSMA (alpha smooth muscle actin) in a TGFβ (transforming growth factor beta)2-dependent mechanism. Our results have identified RGS5 as a crucial regulator of pericyte function during cardiac aging. The deletion of RGS5 causes cardiac dysfunction and induces myocardial fibrosis, one of the hallmarks of cardiac aging.

High-intensity interval training improves respiratory and cardiovascular adjustments before and after initiation of exercise.

Purpose: High-intensity interval training (HIIT) may induce training-specific physiological adaptations such as improved respiratory and cardiovascular adjustments before and after the onset of high-intensity exercise, leading to improved exercise performance during high-intensity exercise. The present study investigated the effects of HIIT on time-dependent cardiorespiratory adjustment during maximal exercise and before and after initiation of high-intensity exercise, as well as on maximal exercise performance. Methods: 21 healthy male college students were randomly assigned to HIIT group (n = 11) or control group (n = 10). HIIT group performed training on a cycle ergometer once a week for 8 weeks. The training consisted of three bouts of exercise at 95% maximal work rate (WRmax) until exhaustion. Before and after the HIIT program, dynamic cardiorespiratory function was investigated by ramp and step exercise tests, and HIIT-induced cardiac morphological changes were assessed using echocardiography. Results: HIIT significantly improved not only maximal oxygen uptake and minute ventilation, but also maximal heart rate (HR), systolic blood pressure (SBP), and time to exhaustion in both exercise tests (p < 0.05). Time-dependent increases in minute ventilation (VE) and HR before and at the start of exercise were significantly enhanced after HIIT. During high-intensity exercise, there was a strong correlation between percent change (from before to after HIIT program) in time to exhaustion and percent change in HRmax (r = 0.932, p < 0.001). Furthermore, HIIT-induced cardiac morphological changes such as ventricular wall hypertrophy was observed (p < 0.001). Conclusion: We have demonstrated that HIIT at 95% WRmax induces training-specific adaptations such as improved cardiorespiratory adjustments, not only during maximal exercise but also before and after the onset of high-intensity exercise, improvement of exercise performance mainly associated with circulatory systems.

Cardiac remodeling in patients with atrial fibrillation reversing bradycardia-induced cardiomyopathy: A case report

BACKGROUND Bradycardia-induced cardiomyopathy (BIC), which is a disease resulting from bradycardia, is characterized by cardiac chamber enlargement and diminished cardiac function. The correction of bradycardia can allow for significant improvements in both cardiac function and structure; however, this disease has been infrequently documented. In this case, we conducted a longitudinal follow-up of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention. CASE SUMMARY A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7. Since she had no obvious symptoms, she did not receive any treatment to improve her bradycardia during the 42-year follow-up, except for the implantation of a temporary pacemaker during labor induction surgery. As time progressed, the patient's heart gradually expanded due to her low ventricular rate, and she was diagnosed with BIC. In 2014, the patient developed atrial fibrillation, her ventricular rate gradually increased, and her heart shape gradually returned to normal. This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years, introduces another possible outcome of BIC, and emphasizes the importance of early intervention in treating BIC. CONCLUSION BIC can induce atrial fibrillation, causing an increased ventricular rate and leading to positive cardiac remodeling.

Activation of adenosine A2B receptor alleviates myocardial ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress and restoring autophagy flux

Myocardial ischemia-reperfusion injury (MIRI) poses a significant threat to patients with coronary heart disease. Adenosine A2A receptors have been known as a protective role in MIRI by regulating autophagy, so we assumed that activation of adenosine A2B receptor (A2BAR) might exert a similar effect during MIRI and underlying mechanism be related to proteostasis maintenance as well. In situ hearts were subjected to 30 min of ischemia and 120 min of reperfusion (IR), while invitro cardiomyocytes from neonatal rats experienced 6 h of oxygen-glucose deprivation followed by 12 h of reoxygenation (OGDR). Initially, we observed that post-ischemia-reperfusion induced autophagy flux blockade and ERS both in vivo and in vitro, evident through the increased expression of p62, LC3II, and BIP, which indicated the deteriorated proteostasis. We used a selective A2BAR agonist, Bay 60–6583, to explore the positive effects of A2BAR on cardiomyocytes and found that A2BAR activation rescued damaged cardiac function and morphological changes in the IR group and improved frail cell viability in the OGDR group. The A2BAR agonist also alleviated the blockage of autophagic flux, coupled with augmented ERS in the IR/OGDR group, which was reassured by using an autophagy inhibitor chloroquine (CQ) and ERS inhibitor (4-PBA) in vitro. Additionally, considering cAMP/PKA as a well-known downstream effector of A2BAR, we utilized H89, a selective PKA inhibitor. We observed that the positive efficacy of Bay 60–6583 was inhibited by H89. Collectively, our findings demonstrate that the A2BAR/cAMP/PKA signaling pathway exerts a protective role in MIRI by mitigating impaired autophagic flux and excessive ERS.

Right-sided infective endocarditis or thrombus? Report of two cases diagnosed by transthoracic echocardiography

BackgroundRight-sided infective endocarditis (RSIE) is a relatively uncommon condition which is difficult to distinguish from thrombus, particularly when the site of infection or the patient’s symptoms are atypical. There have been few reports exploring the differential diagnostic and analytical features between RSIE and thrombus.Case presentationHere, we presented two cases of RSIE—one involving the tricuspid valve and the other affecting the pulmonary artery. Notably, the second case was initially misdiagnosed as thrombus based on the findings of by computed tomography angiography(CTA).ConclusionsVegetation and thrombus can be distinguished according to the nature of the mass, its attachment location, and the clinical manifestation. Echocardiography can observe both the location and size of the mass, and the dynamic changes in cardiac hemodynamics and cardiac morphology, thereby facilitating an effective distinction between vegetation and thrombus.

Acute changes in cardiac dimensions, function, and longitudinal mechanics in healthy individuals with and without high-altitude induced pulmonary hypertension at 4559m.

High-altitude pulmonary hypertension (HAPH) has a prevalence of approximately 10%. Changes in cardiac morphology and function at high altitude, compared to a population that does not develop HAPH are scarce. Four hundred twenty-one subjects were screened in a hypoxic chamber inspiring a FiO2 =12% for 2h. In 33 subjects an exaggerated increase in systolic pulmonary artery pressure (sPAP) could be confirmed in two independent measurements. Twenty nine of these, and further 24 matched subjects without sPAP increase were examined at 4559m by Doppler echocardiography including global longitudinal strain (GLS). SPAP increase was higher in HAPH subjects (∆=10.2vs. ∆=32.0mm Hg, p<.001). LV eccentricity index (∆=.15vs. ∆=.31, p=.009) increased more in HAPH. D-shaped LV (0 [0%] vs. 30 [93.8%], p=.00001) could be observed only in the HAPH group, and only in those with a sPAP ≥50mm Hg. LV-EF (∆=4.5vs. ∆=6.7%, p=.24) increased in both groups. LV-GLS (∆=1.2vs. ∆=1.1 -%, p=.60) increased slightly. RV end-diastolic (∆=2.20vs. ∆=2.7cm2 , p=.36) and end-systolic area (∆=2.1vs. ∆=2.7cm2 , p=.39), as well as RA end-systolic area index (∆=-.9vs. ∆=.3cm2 /m2 , p=.01) increased, RV-FAC (∆=-2.9vs. ∆=-4.7%, p=.43) decreased, this was more pronounced in HAPH, RV-GLS (∆=1.6vs. ∆=-.7 -%, p=.17) showed marginal changes. LV and LA dimensions decrease and left ventricular function increases at high-altitude in subjects with and without HAPH. RV and RA dimensions increase, and RV longitudinal strain increases or remains unchanged in subjects with HAPH. Changes are negligible in those without HAPH.

Evaluation of the changes in cardiac morphology of fetuses with congenital heart disease using fetalHQ

Objective: To evaluate the changes in cardiac morphology of fetuses with congenital heart disease (CHD) using the fetal heart quantitative technique (fetalHQ). Methods: A total of 20 normal pregnant women (control group) and 20 pregnant women suspected of fetal CHD (case group) were included in this study. The dynamic images of the four-chamber view of the fetal heart were recorded and analyzed using fetalHQ. The global sphericity index (GSI) and 24-segment SI of the two groups were compared. The differences in the left and right ventricular 24-segment SI for each group were investigated. Results: There was no statistically significant difference in the GSI between the two groups (p > 0.05). The difference in the SI values of left ventricular segments 1–2 between the case group and control group was statistically significant (all p < 0.05), while the intergroup difference in SI of left ventricular segments 3–24 was not significant (all p > 0.05). The SI of the 24 segments of the right ventricle showed no significant intergroup difference (all p > 0.05). The difference in the left and right ventricular 24-segment SI in the case group did not reach statistical significance (all p > 0.05). In the control group, the SI values between the left and right ventricles were significantly different in segments 18–24 (all p < 0.05), and no significant difference was found in segments 1–17 (all p > 0.05). There was a statistically significant intergroup difference in the percentage of unusual left ventricular SI, determined based on Z-score (p < 0.05), and the percentage of outliers for the right ventricle between the two groups showed no significant difference (p > 0.05). Conclusion: The fetalHQ is regarded as a straightforward and reliable approach for assessing the cardiac GSI and 24-segment SI of left and right ventricles in fetuses diagnosed with CHD. While CHD may not significantly impact the overall shape of the fetal heart or the geometric shape of the right ventricle, in this study, a notable increase in SI values for the left ventricular 1–2 segments was observed, indicating a more flattened ventricular chamber. Additionally, the morphological distinctions between the left and right ventricles in fetuses with CHD are no longer discernible.

Long non-coding RNA SNHG18 epigenetic regulates ferroptosis in acute myocardial infarction

Abstract Background Loss of terminally differentiated cardiomyocytes is a key pathogenic factor for the occurrence of acute myocardial infarction (AMI) and the development of lethal heart failure. LncRNAs have been confirmed to be critical in regulating AMI, besides, recently published studies disclosed that ferroptosis is a new form of programmed cell death that contributes to AMI. However, whether LncRNAs are involved in the regulation of ferroptosis and correlated underlying mechanisms in AMI remains unknown. Purpose Our present study is to investigate LncRNA that regulates cardiomyocyte ferroptosis in AMI and uncover the potential mechanisms. Method RNA-sequencing and bioinformatical analyses were conducted to identify the candidate LncRNAs for AMI. Adenovirus for LncRNA knockout and overexpression were constructed to alter the SNHG18 expression of cardiomyocytes in vitro. Cardiomyocyte-specific knockout and overexpression mice were also constructed to alter SNHG18 expression in vivo. Ferroptosis characteristic measurement, including glutathione peroxidase 4 (GPX4), Ferritin heavy chain (FTH-1), ptgs2, MDA, ROS, Fe2+, glutathione, and mitochondrial morphology, was performed to verify the ability of SNHG18 to regulate the ferroptosis of cardiomyocytes. Cardiac morphological, structural, functional, and hemodynamic changes as well as the viability of cardiomyocytes were also measured to assess the effect of SNHG18 on AMI. RNA-pulldown+Mass spectrometry, RNA immunoprecipitation were performed to identify the specific binding factors of SNHG18. Results RNA-sequencing results revealed the expression of SNHG18 was significantly and persistently elevated from 3 to 7 days after AMI. SNHG18 was mainly enriched in the nucleus of cardiomyocytes. Besides, the down-regulation of SNHG18 could specifically alleviate the cell viability loss caused by ferroptosis inducers. Thereafter, gain- and loss-of-function experiments were performed both in vitro and in vivo. Functionally, SNHG18 knockout dramatically enhanced cardiomyocyte vitality, reduced infarct size, improved cardiac performance and alleviated cardiac fibrosis by mitigating cardiomyocyte ferroptosis. However, enforced SNHG18 expression resulted in the opposite effects. Mechanistically, the subunit RBBP4 that forms the PRC2 (Polycomb Repressive Complex 2) complex was a direct target of SNHG18, which was also confirmed by RIP assays. In addition, Chip-PCR analysis also demonstrated that PRC2 could directly bind to the promoter region of the GPX4 and FTH1 gene, thus altering the level of H3K27me3 and inhibiting their transcription. Moreover, subsequent rescue experiments further verified that SNHG18 regulated the expression of GPX4 and FTH1 to ameliorate AMI-induced cardiomyocyte ferroptosis in a PRC2-dependent manner. Conclusion This study demonstrates that SNHG18-PRC2-GPX4/FTH1 pathway is a promising therapeutic target for the treatment of AMI by ameliorating cardiomyocyte ferroptosis.

Dynamic changes in cardiac morphology, function, and diffuse myocardial fibrosis duration of diabetes in type 1 and type 2 diabetic mice models using 7.0 T CMR and echocardiography.

Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Hence, early detection of cardiac changes by imaging is crucial to reducing cardiovascular complications. Early detection of cardiac changes is crucial to reducing cardiovascular complications. The study aimed to detect the dynamic change in cardiac morphology, function, and diffuse myocardial fibrosis(DMF) associated with T1DM and T2DM mice models. 4-week-old C57Bl/6J male mice were randomly divided into control (n=30), T1DM (n=30), and T2DM (n=30) groups. A longitudinal study was conducted every 4 weeks using serial 7.0T CMR and echocardiography imaging. Left ventricular ejection fraction (LV EF), tissue tracking parameters, and DMF were measured by cine CMR and extracellular volume fraction (ECV). Global peak circumferential strain (GCPS), peak systolic strain rate (GCPSSR) values were acquired by CMR feature tracking. LV diastolic function parameter (E/E') was acquired by echocardiography. The correlations between the ECV and cardiac function parameters were assessed by Pearson's test. A total of 6 mice were included every 4 weeks in control, T1DM, and T2DM groups for analysis. Compared to control group, an increase was detected in the LV mass and E/E' ratio, while the values of GCPS, GCPSSR decreased mildly in DM. Compared to T2DM group, GCPS and GCPSSR decreased earlier in T1DM(GCPS 12W,P=0.004; GCPSSR 12W,P=0.04). ECV values showed a significant correlation with GCPS and GCPSSR in DM groups. Moreover, ECV values showed a strong positive correlation with E/E'(T1DM,r=0.757,P<0.001;T2DM, r=0.811,P<0.001). The combination of ECV and cardiac mechanical parameters provide imaging biomakers for pathophysiology, early diagnosis of cardiac morphology, function and early intervention in diabetic cardiomyopathy in the future.

EP01.39: Evaluation of fetal cardiac morphological and functional changes in hypertensive disorders of pregnancy by fetal heart quantification technique

EP01.39: Evaluation of fetal cardiac morphological and functional changes in hypertensive disorders of pregnancy by fetal heart quantification technique

Effect of thyroid hormone replacement treatment on cardiac diastolic function in adult patients with subclinical hypothyroidism: a meta-analysis.

Although subclinical hypothyroidism (SCH) is related to abnormalities in left ventricular diastolic function, the use of levothyroxine as a regular treatment remains debatable. This meta-analysis aimed to determine whether thyroid hormone replacement therapy affects cardiac diastolic function in patients with SCH as measured by echocardiography. This meta-analysis included a search of the EMBASE, PubMed, Web of Science, and Cochrane Library databases from their inception to May 18, 2023, for studies analyzing cardiac morphology and functional changes in patients with SCH before and after thyroid hormone replacement. The outcome measures were cardiac morphology and diastolic and overall cardiac function, as assessed using ultrasound parameters (including ventricular wall thickness, chamber size, mitral wave flow, tissue Doppler, and speckle tracking). The quality of the studies was assessed using the Newcastle-Ottawa Scale. The standard mean differences (MDs) and 95% confidence intervals (CI) were calculated using fixed- or random-effects models. Seventeen studies met the inclusion criteria. A total of 568 patients participated and completed the follow-up. All studies specifically stated that serum thyrotropin levels returned to normal by the end of the study period. Compared with baseline levels, no significant morphological changes were observed in the heart. In terms of diastolic function, we discovered that the ratios of E-velocity to A-velocity (E/A) had greatly improved after thyroid hormone replacement therapy, whereas the ratios of the mitral inflow E wave to the tissue Doppler e' wave (E/e') had not. Global longitudinal strain (GLS) increased significantly after treatment with levothyroxine. In adult patients with SCH, thyroid hormone supplementation can partially but not completely improve parameters of diastolic function during the observation period. This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement, an updated guideline for reporting systematic reviews (11) and was registered with INPLASY (INPLASY202320083). https://inplasy.com/inplasy-2023-2-0083.

Abstract P3175: Mitochondrial Fission And Extracellular Mitochondria Mediate Cardiac Dysfunction In Obesity Induced Cardiomyopathy

Background: Recent studies have demonstrated that dysregulation of mitochondrial dynamics, including excessive mitochondrial fission, lead to extracellular release of damaged mitochondria (exMito) as an alternate mechanism for mitochondrial quality control. However, the exact role of this mechanism on obesity cardiomyopathy (OCM) has not been explored. This project aims to determine if Drp1/Fis1 dependent excessive mitochondrial fission mediates the release of damaged mitochondria and propagate cardiomyocyte injury in OCM. Methods: H9c2 cardiomyoblast were treated with 200 μM palmitate (PA) to induce lipotoxicity. C57BL6/J mice were subjected to a high-fat diet (HFD) for 12 weeks to induce OCM. Changes in cardiac Drp1 activity, mitochondrial morphology, bioenergetics and contractile function was evaluated. Simultaneously, exMito were collected and characterized from supernatant and plasma. Using peptide P110 co-treatment , we determined the impact of pharmacologic inhibition of Drp1/Fis1 dependent mitochondrial fission on cardiac mitochondrial function as well as the quality and quantity of exMito. Results: H9c2 cells treated with PA demonstrated excessive mitochondrial fission, increased oxidative stress and decreased ATP level. The excessive mitochondrial fission seen following PA treatment was associated with the release of damaged exMito. The exMito isolated from PA treated cells were noted to mediate cytotoxicity to healthy H9c2s independent of PA. P110 treatment was protective against PA mediated mitochondrial damage, represented by improved bioenergetic profile, increased ATP and lower oxidative stress. P110 treatment also lowered the release of damaged mitochondria from PA treated H9c2s. Similarly, treatment of HFD mice with P110, improved mitochondrial function and glucose utilization, exMito release and subsequently improved cardiomyocyte contractile function. Conclusion: Lipotoxicity induced mitochondrial fission, disrupted mitochondrial function leading to release of exMito. P110 limited lipotoxicity mediated alterations in mitochondrial dynamics, mitochondrial function and exMito, and then improved cardiac function. Therefore, pathologic fission and exMito may play a critical role in OCM.

Comparison of fetal and neonatal cardiac morphology between the infants of mothers with well-controlled gestational diabetes mellitus and normal controls.

To compare fetal and neonatal cardiac morphology in fetuses of mothers with gestational diabetes mellitus (GDM) with the controls. Pregnant women at average risk of GDM underwent 100-g, 3-h-OGTT at 24-28weeks of gestation for diagnosis of GDM. Both GDM group and the control group underwent fetal echocardiography at 32-36weeks to assess cardiac dimensions. The neonates underwent echocardiography within 48h after birth to assess cardiac morphology. A total of 154 pregnant women were recruited, including 60 in the GDM group and 94 in the control group. All of the study group were well controlled for GDM. Most baseline characteristics of both groups were comparable. All obstetric outcomes were not significantly different between the two groups. Morphological cardiac dimensions in the fetuses and newborns of both groups were also not significant different. Subgroup analysis in the study group showed no significantly different in cardiac morphology between the group with diet control and that of insulin control. Fetal and neonatal cardiac morphologic changes among mothers with well-controlled GDM are not significantly different from those in the controls. It is possible that good control of maternal blood glucose can prevent fetal and neonatal cardiac abnormalities.

Endogenous interleukin-22 prevents cardiac rupture after myocardial infarction in mice.

Myocardial infarction (MI) can result in fatal myocardial rupture or heart failure due to adverse remodeling and dysfunction of the left ventricle. Although recent studies have shown that exogenous interleukin (IL)-22 shows cardioprotective effect after MI, the pathophysiological significance of endogenous IL-22 is unknown. In this study, we investigated the role of endogenous IL-22 in a mouse model of MI. We produced MI model by permanent ligation of the left coronary artery in wild-type (WT) and IL-22 knock-out (KO) mice. The post-MI survival rate was significantly worse in IL-22KO mice than in WT mice due to a higher rate of cardiac rupture. Although IL-22KO mice exhibited a significantly greater infarct size than WT mice, there was no significant difference in left ventricular geometry or function between WT and IL-22KO mice. IL-22KO mice showed increase in infiltrating macrophages and myofibroblasts, and altered expression pattern of inflammation- and extracellular matrix (ECM)-related genes after MI. While IL-22KO mice showed no obvious changes in cardiac morphology or function before MI, expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were increased, whereas that of tissue inhibitor of MMPs (TIMP)-3 was decreased in cardiac tissue. Protein expression of IL-22 receptor complex, IL-22 receptor alpha 1 (IL-22R1) and IL-10 receptor beta (IL-10RB), were increased in cardiac tissue 3 days after MI, regardless of the genotype. We propose that endogenous IL-22 plays an important role in preventing cardiac rupture after MI, possibly by regulating inflammation and ECM metabolism.

Fetal Cardiac Function at Midgestation in Women Who Subsequently Develop Gestational Diabetes

Fetuses in women with gestational diabetes (GD) compared with those without GD show evidence of subclinical cardiac functional and morphological changes. However, it is uncertain whether glycemia or the adverse maternal underlying risk factor profile is the main driver for fetal cardiac remodeling. To assess cardiac morphology and function at midgestation in fetuses of mothers prior to development of GD and compare them with those of unaffected controls. During this prospective nonintervention screening study at 19 to 23 weeks' gestation, fetal cardiac morphology and function were assessed in all participants. Pregnancy complications were obtained from the medical records of the women. Fetal cardiac morphology and function were assessed in all participants at Harris Birthright Research Institute at King's College Hospital, London, United Kingdom. Participants included pregnant women with singleton pregnancy who attended their routine fetal ultrasound examination at midgestation and agreed to participate in the Advanced Cardiovascular Imaging Study in pregnancy. Comparison of fetal cardiac morphology and function between mothers who subsequently developed GD and those who did not develop GD. This was a prospective nonintervention screening study of 5620 women with singleton pregnancies at 19 to 23 weeks' gestation. Conventional and more advanced echocardiographic modalities, such as speckle tracking, were used to assess fetal cardiac function in the right and left ventricle. The morphology of the fetal heart was assessed by calculating the right and left sphericity index. The 5620 included patients had a mean age of 33.6 years. In 470 cases, the women were diagnosed with GD after the midgestation echocardiographic assessment (8.4%). Women with GD, compared with the non-GD group, were older, had higher BMI, higher prevalence of family history of diabetes, non-White ethnicity, chronic hypertension, and GD in a previous pregnancy. In fetuses of the GD group compared with the non-GD group, there was mild increase in interventricular millimeter thickness (0.04; 95% CI, 0.03-0.06 mm) and left atrial area (0.04; 95% CI, 0.04-0.05), whereas left and right functional indices were comparable between groups with the exception of left ventricular ejection fraction, which was marginally improved in the GD group (0.02; 95% CI, 0.03-0.03). This study demonstrates that prior to development of GD, there was mild alteration in fetal cardiac morphology without affecting cardiac function. This suggests that the adverse maternal risk factor profile and not only the glycemia might contribute to cardiac remodeling noted in fetuses of women with GD.

The emerging roles of Shank3 in cardiac function and dysfunction.

Shank3 is a member of the Shank family proteins (Shank1-3), which are abundantly present in the postsynaptic density (PSD) of neuronal excitatory synapses. As a core scaffold in the PSD, Shank3 plays a critical role in organizing the macromolecular complex, ensuring proper synaptic development and function. Clinically, various mutations of the SHANK3 gene are causally associated with brain disorders such as autism spectrum disorders and schizophrenia. However, recent in vitro and in vivo functional studies and expression profiling in various tissues and cell types suggest that Shank3 also plays a role in cardiac function and dysfunction. For example, Shank3 interacts with phospholipase Cβ1b (PLCβ1b) in cardiomyocytes, regulating its localization to the sarcolemma and its role in mediating Gq-induced signaling. In addition, changes in cardiac morphology and function associated with myocardial infarction and aging have been investigated in a few Shank3 mutant mouse models. This review highlights these results and potential underlying mechanisms, and predicts additional molecular functions of Shank3 based on its protein interactors in the PSD, which are also highly expressed and function in the heart. Finally, we provide perspectives and possible directions for future studies to better understand the roles of Shank3 in the heart.

Effects and mechanism of Compound Qidan Formula on rats with HFpEF induced by hypertension and diabetes mellitus based on Ang Ⅱ/TGF-β1/Smads signaling pathway

Ethnopharmacological relevanceCompound Qidan Formula is composed of traditional Chinese herbs and has a good curative effect in the clinical application of cardiovascular diseases such as heart failure. However, its potential molecular mechanisms of action remain highly unknown. Aim of the studyTo observe the effect of Compound Qidan Formula on cardiac function in rats with HFpEF induced by hypertension and diabetes mellitus, and to explore its mechanism from Ang Ⅱ/TGF-β1/Smads signaling pathway. Materials and methodsA total of 50 SPF-grade spontaneously hypertensive rats (SHR) aged 14 weeks, fed with a high-fat and high-sucrose diet for 16 weeks, and after 2 weeks of a high-fat and high-sucrose diet, 1% streptozotocin (25 mg/kg body weight)was injected intraperitoneally to establish a rat model of HFpEF induced by hypertension and diabetes mellitus. After 8 weeks of intragastric administration, the changes in cardiac morphology and function were evaluated by echocardiography after anesthesia; the heart tissue was taken and embedded in paraffin for Masson staining, and the pathomorphological changes of left atrial tissue were observed under the optical microscope; the mRNA transcription levels of Ang Ⅱ, AT1R, TGF-β1, Smad2, Smad3, MMP-9 and TIMP-1in left atrial tissue of rats were detected by RT-PCR; and the protein expressions were detected by Western blot. ResultsCompared with the SHR-DM group, the QD-Low and QD-High groups significantly decreased the left atrial (LA) anteroposterior diameter and interventricular septal thickness (IVST) and improved the peak velocity of mitral valve blood flow in early diastolic period (E), maximum mitral valve blood flow in systolic period (A), mitral ring myocardial movement velocity in early diastolic period (e’) and E/e' ratio; the QD-High group significantly improved the E/A ratio, left atrial ejection fraction (LAEF) and left ventricular ejection fraction(LVEF). Masson staining showed that compared with the WKY group, the SHR-DM group had obvious myocardial histomorphological lesions. Compared with the SHR-DM group, the Compound Qidan Formula groups significantly improved cardiomyocyte hypertrophy and disordered arrangement and inhibited myocardial fibrosis; the mRNA expression levels of Ang Ⅱ, AT1R, TGF-β1, Smad2, Smad3, and MMP-9 in myocardial tissue of Compound Qidan Formula groups were significantly decreased, and the mRNA expression level of TIMP-1 was significantly increased. The protein expression levels of Ang Ⅱ, TGF-β1, P-Smad2/3, and MMP-9 were significantly decreased. ConclusionCompound Qidan Formula, composed of traditional Chinese herbs, can significantly improve cardiac function, improve atrial and ventricular remodeling, and prevent myocardial fibrosis and hypertrophy in rats with HFpEF induced by hypertension and diabetes mellitus. The mechanism may be related to regulating the Ang Ⅱ/TGF-β1/Smad2/3 signaling pathway.