International heart journal最新文献

The impact of tolvaptan and low-dose dopamine on heart failure (HF) patients with acute kidney injury (AKI) remains uncertain from a clinical standpoint.

HF patients with AKI were selected and divided in a 1:1 fashion into the dopamine combined with the tolvaptan group (DTG), the tolvaptan group (TG), and the control group (CG). According to the standard of care, TG received tolvaptan 15 mg orally daily for a week. DTG received combination treatment, including 7 consecutive days of dopamine infusion (2 μg/kg・minutes) and oral tolvaptan 15 mg. Venous blood and urine samples were taken before and after therapy. The primary endpoint was the cardiorenal serological index after 7 days of treatment.

Sixty-five patients were chosen randomly for the DTG (22 patients), TG (20 patients), and CG (23 patients), which were similar before the treatment. The serum indexes related to cardiac function (N-terminal probrain natriuretic peptide and cardiac troponin I) in DTG were decreased, compared with TG and CG (P < 0.05). Furthermore, the serological markers of renal function (serum cystatin C, serum creatinine, and neutrophil gelatinase-associated lipocalin) in DTG were lower than those in TG and CG (P < 0.05). There was no significant difference in the incidence of adverse reactions among groups.

Low-dose dopamine combined with tolvaptan can markedly improve patients' cardiac and renal function. This may be considered a new therapeutic method for HF patients with AKI.

This study aimed to investigate the molecular mechanisms underlying the protective effects of cyclooxygenase (cox) inhibitors against myocardial hypertrophy.

Rat H9c2 cardiomyocytes were induced by mechanical stretching. SD rats underwent transverse aortic constriction to induce pressure overload myocardial hypertrophy. Rats were subjected to echocardiography and tail arterial pressure in 12W. qPCR and western blot were used to detect the expression of Notch-related signaling. The inflammatory factors were tested by ELISA in serum, heart tissue, and cell culture supernatant.

Compared with control, levels of pro-inflammatory cytokines IL-6, TNF-α, and IL-1β were increased and anti-inflammatory cytokine IL-10 was reduced in myocardial tissues and serum of rat models. Levels of Notch1 and Hes1 were reduced in myocardial tissues. However, cox inhibitor treatment (aspirin and celecoxib), the improvement of exacerbated myocardial hypertrophy, fibrosis, dysfunction, and inflammation was parallel to the activation of Notch1/Hes1 pathway. Moreover, in vitro experiments showed that, in cardiomyocyte H9c2 cells, application of ~20% mechanical stretching activated inflammatory mediators (IL-6, TNF-α, and IL-1β) and hypertrophic markers (ANP and BNP). Moreover, expression levels of Notch1 and Hes1 were decreased. These changes were effectively alleviated by aspirin and celecoxib.

Cox inhibitors may protect heart from hypertrophy and inflammation possibly via the Notch1/Hes1 signaling pathway.

This study aimed to explore the expression of long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in patients with acute myocardial infarction (AMI) and its inflammatory regulation mechanism through miR-211/interleukin 10 (IL-10) axis.

A total of 75 participants were enrolled in this study: 25 healthy people in the control group, 25 patients with stable angina pectoris (SAP) in the SAP group, and 25 patients with AMI in the AMI group. Real-time qPCR was used to detect mRNA expression levels of NEAT1, miR-211, and IL-10. The interaction between miR-211, NEAT1, and IL-10 was confirmed by dual-luciferase reporter assay, and protein expression was detected using western blot.

High expression of NEAT1 in peripheral blood mononuclear cells (PBMCs) of patients with AMI was negatively related to serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), IL-6, and IL-1β and was positively correlated with left ventricular ejection fraction (LVEF). In THP-1 cells, miR-211 was confirmed to target and inhibit IL-10 expression. NEAT1 knockdown and miR-211-mimic markedly decreased IL-10 protein levels, whereas anti-miR-211 markedly increased IL-10 protein levels. Importantly, miR-211 level was negatively related to NEAT1 and IL-10 levels, whereas IL-10 level was positively related to the level of NEAT1 expression in PBMCs of patients with AMI.

LncRNA NEAT1 was highly expressed in PBMCs of patients with AMI, and NEAT1 suppressed inflammation via miR-211/IL-10 axis in PBMCs of patients with AMI.

Cardiac ryanodine receptor (RyR2) gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Conversely, RyR2 loss-of-function mutations cause a new disease entity, termed calcium release deficiency syndrome (CRDS), which may include RYR2-related long QT syndrome (LQTS). Importantly, unlike CPVT, patients with CRDS do not always exhibit exercise- or epinephrine-induced ventricular arrhythmias, which precludes a diagnosis of CRDS. Here we report a boy and his father, who both experienced exercise-induced cardiac events and harbor the same RYR2 E4107A variant. In the boy, an exercise stress test (EST) and epinephrine provocation test (EPT) did not induce any ventricular arrhythmias. QTc was slightly prolonged (QTc: 474 ms), and an EPT induced QTc prolongation (QTc-baseline: 466 ms, peak: 532 ms, steady-state: 527 ms). In contrast, in his father, QTc was not prolonged (QTc: 417 ms), and neither an EST nor EPT induced QTc prolongation. However, an EST induced multifocal premature ventricular contraction (PVC) bigeminy and bidirectional PVC couplets. Thus, they exhibited distinct clinical phenotypes: the boy exhibited LQTS (or CRDS) phenotype, whereas his father exhibited CPVT phenotype. These findings suggest that, in addition to the altered RyR2 function, other unidentified factors, such as other genetic, epigenetic, and environmental factors, and aging, may be involved in the diverse phenotypic manifestations. Considering that a single RYR2 variant can cause both CPVT and LQTS (or CRDS) phenotypes, in cascade screening of patients with CPVT and CRDS, an EST and EPT are not sufficient and genetic analysis is required to identify individuals who are at increased risk for life-threatening arrhythmias.

Cardiomyocyte hypertrophy plays a crucial role in heart failure development, potentially leading to sudden cardiac arrest and death. Previous studies suggest that micro-ribonucleic acids (miRNAs) show promise for the early diagnosis and treatment of cardiomyocyte hypertrophy.

To investigate the miR-378 expression in the cardiomyocyte hypertrophy model, reverse transcription-polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence tests were conducted in angiotensin II (Ang II)-induced H9c2 cells and Ang II-induced mouse model of cardiomyocyte hypertrophy. The functional interaction between miR-378 and AKT2 was studied by dual-luciferase reporter, RNA pull-down, Western blot, and RT-qPCR assays.

The results of RT-qPCR analysis showed the downregulated expression of miR-378 in both the cell and animal models of cardiomyocyte hypertrophy. It was observed that the introduction of the miR-378 mimic inhibited the hypertrophy of cardiomyocytes induced by Ang II. Furthermore, the co-transfection of AKT2 expression vector partially mitigated the negative impact of miR-378 overexpression on Ang II-induced cardiomyocytes. Molecular investigations provided evidence that miR-378 negatively regulated AKT2 expression by interacting with the 3' untranslated region (UTR) of AKT2 mRNA.

Decreased miR-378 expression and AKT2 activation are linked to Ang II-induced cardiomyocyte hypertrophy. Targeting miR-378/AKT2 axis offers therapeutic opportunity to alleviate cardiomyocyte hypertrophy.

Cholesterol crystal (CC) embolism is a disease in which CCs from atherosclerotic lesions embolize peripheral arteries, causing organ dysfunction. In this case, a patient with spontaneously ruptured aortic plaques (SRAPs) identified by non-obstructive general angioscopy (NOGA) may have developed a CC embolism. This is the first report of a CC embolism in a patient with SRAPs identified using NOGA, which further supports the previously speculated pathogenesis of CC embolism due to SRAPs.

Myocardial infarction/reperfusion (I/R) injury significantly impacts the health of older individuals. We confirmed that the level of lncRNA Peg13 was downregulated in I/R injury. However, the detailed function of Peg13 in myocardial I/R injury has not yet been explored.

To detect the function of Peg13, in vivo model of I/R injury was constructed. RT-qPCR was employed to investigate RNA levels, and Western blotting was performed to assess levels of endoplasmic reticulum stress and apoptosis-associated proteins. EdU staining was confirmed to assess the cell proliferation.

I/R therapy dramatically produced myocardial injury, increased the infarct area, and decreased the amount of Peg13 in myocardial tissues of mice. In addition, hypoxia/reoxygenation (H/R) notably induced the apoptosis and promoted the endoplasmic reticulum (ER) stress of HL-1 cells, while overexpression of Peg13 reversed these phenomena. Additionally, Peg13 may increase the level of Sirt1 through binding to miR-34a. Upregulation of Peg13 reversed H/R-induced ER stress via regulation of miR-34a/Sirt1 axis.

LncRNA Peg13 reduces ER stress in myocardial infarction/reperfusion injury through mediation of miR-34a/Sirt1 axis. Hence, our research might shed new lights on developing new strategies for the treatment of myocardial I/R injury.

Endothelial cell dysfunction is the main pathology of atherosclerosis (AS). Sirtuin 6 (SIRT6), a deacetylase, is involved in AS progression. This study aimed to investigate the impacts of SIRT6 on the pyroptosis of endothelial cells and its underlying mechanisms. ApoE−/− mice were fed a high-fat diet (HFD) to establish the AS mouse model, atherosclerotic lesions were evaluated using oil red O staining, and blood lipids and inflammatory factors were measured using corresponding kits. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish the cell model, and pyroptosis was evaluated by flow cytometry, ELISA, and western blot. Immunoprecipitation (IP), co-IP, western blot, and immunofluorescence were used to detect the molecular mechanisms. The results showed that SIRT6 expression was downregulated in the blood of HFD-induced mice and ox-LDL-induced HUVECs. Overexpression of SIRT6 reduced atherosclerotic lesions, blood lipids, and inflammation in vivo and suppressed pyroptosis of HUVECs in vitro. Moreover, SIRT6 interacted with ASC to inhibit the acetylation of ASC, thus, reducing the interaction between ASC and NLRP3. Moreover, SIRT6 inhibits endothelial cell pyroptosis in the aortic roots of mice by deacetylating ASC. In conclusion, SIRT6 deacetylated ASC to inhibit its interaction with NLRP3 and then suppressed pyroptosis of endothelial cells, thus, decelerating the progression of AS. The findings provide new insights into the function of SIRT6 in AS.

A 55-year-old man presented to the emergency department with worsening shortness of breath 1 month after a gastrointestinal bleed. He had congestive heart failure, and an electrocardiogram suggested ischemic heart disease involvement. Echocardiography revealed a ventricular septal defect complicated by a left ventricular aneurysm in the inferior-posterior wall. Conservative treatment was started, but hemodynamic collapse occurred on the third day of admission and coronary angiography revealed a revascularizing lesion in the right fourth posterior descending coronary artery. Subsequently, his hemodynamic status continued to deteriorate, even with an Impella CP^® heart pump, so ventricular septal defect patch closure and left ventricular aneurysm suture were performed. His condition improved and he was discharged on day 23 of admission and was not readmitted within 6 months after the procedure. Hemodynamic management of ventricular septal defects requires devices that reduce afterload, and clinicians should be aware of the risk of myocardial infarction after gastrointestinal bleeding.

The elevated risk of cardiovascular disease (CVD) in cancer patients and survivors is likely the result of normal age-related pathologies coupled with the direct and indirect effects of cancer therapy that extend across multiple systems. The purpose of this study was to investigate the impact of cardiac rehabilitation (CR) on CVD patients with a history of cancer.

In this study, patients who had participated in the outpatient CR program were enrolled and were divided into 2 groups (cancer survivor group and no-cancer group) based on their history of cancer. The cardiopulmonary exercise test (CPET) was performed at the beginning (baseline) and at the end of the CR program (follow-up). The results of CPET at baseline and those at follow-up were analyzed retrospectively.

A total of 105 patients were analyzed in this study. The cancer survivor group had 25 patients, and the non-cancer group 80. At baseline, peak oxygen uptake (peak VO₂) (14.7 [11.9 to 17.6] mL/kg/minute versus 11.3 [9.7 to 14.7] mL/kg/minute; P = 0.003) was significantly lower in cancer survivors. The percent changes in peak VO₂ between baseline and follow-up were not significantly different between the 2 groups (7.9 % [−11.5 to 24.5] versus 9.4 % [−7.5 to 27.3] P = 0.520).

The percent changes in peak VO₂ of CR participants were not significantly different despite their cancer history.