SS-31 modification alleviates ferroptosis induced by superparamagnetic iron oxide nanoparticles in hypoxia/reoxygenation cardiomyocytes.

Superparamagnetic iron oxide nanoparticles (SPION) are widely used in cardiovascular applications. However, their potential to induce ferroptosis in myocardial cells post-ischemia-reperfusion hinders clinical adoption. We investigated the mechanisms behind SPION-induced cytotoxicity in myocardial cells and explored whether co-loading SPION with SS-31 (a kind of mitochondrial-targeted antioxidant peptide) could counteract this toxicity.

TAK1 Activation by NLRP3 Deficiency Confers Cardioprotection Against Pressure Overload-Induced Cardiomyocyte Pyroptosis and Hypertrophy.

A comprehensive view of the role of NLRP3/caspase-1/GSDMD-mediated pyroptosis in pressure overload cardiac hypertrophy is presented in this study. Furthermore, mitigation of NLRP3 deficiency-induced pyroptosis confers cardioprotection against pressure overload through activation of TAK1, whereas this salutary effect is abolished by inhibition of TAK1 activity, highlighting a previously unrecognized reciprocally regulatory role of NLRP3-TAK1 governing inflammation-induced cell death and hypertrophic growth. Translationally, this study advocates strategies based on inflammation-induced cell death might be exploited therapeutically in other inflammatory and mechanical overload disorders, such as myocardial infarction and mitral regurgitation.

GSDMD-mediated pyroptosis promotes cardiac remodeling in pressure overload.

Background: Gasdermin D (GSDMD) forms membrane pores to execute pyroptosis. But the mechanism of how cardiomyocyte pyroptosis induces cardiac remodeling in pressure overload remains unclear. We investigated the role of GSDMD-mediated pyroptosis in the pathogenesis of cardiac remodeling in pressure overload.

Surgically Induced Cardiac Volume Overload by Aortic Regurgitation in Mouse.

Aortic regurgitation (AR) is a common valvular heart disease that exerts volume overload on the heart and represents a global public health problem. Although mice are widely applied to shed light on the mechanisms of cardiovascular disease, mouse models of AR, especially those induced by surgery, are still paucity. Here, a mouse model of AR was described in detail which is surgically induced by disruption of the aortic valves under high-resolution echocardiography.

Long-term prognostic value of dynamic function assessment of intermediate coronary lesion with computational physiology.

This study sought to investigate the dynamic functional changes of coronary intermediate lesions using quantitative flow ratio (QFR) and its implication on long-term clinical outcomes. Physiology-guided percutaneous coronary intervention in patients with angiographic intermediate lesions has been associated with favorable outcomes. This study consecutively enrolled 1130 patients with deferred intermediate lesions at baseline angiography and subsequently received second-time angiography between 9 months and 2 years later from two centers in China.

Troponin T Elevation After Percutaneous Left Atrial Appendage Occlusion.

Cardiac troponin T (cTNT) has been widely used in detecting cardiac damage. Elevated cTNT level has been reported to be associated with increased mortality in multiple cardiac conditions. It is not uncommon to observe an increased level of cTNT in patients after left atrial appendage occlusion (LAAO).

Involvement of Endoplasmic Reticulum Stress-Mediated Activation of C/EBP Homologous Protein in Aortic Regurgitation-Induced Cardiac Remodeling in Mice.

Aortic regurgitation (AR) is a volume overload disease causing eccentric left ventricular (LV) hypertrophy and eventually heart failure. There is currently no approved drug to treat patients with AR. Endoplasmic reticulum (ER) stress and ER stress-mediated apoptosis is involved in many cardiovascular diseases, but whether they also participate in AR-induced heart failure is still elusive.

Predictors and long-term prognosis of left ventricular aneurysm in patients with acute anterior myocardial infarction treated with primary percutaneous coronary intervention in the contemporary era.

Background: Primary percutaneous coronary intervention (PCI) has been the standard reperfusion strategy for patients with acute myocardial infarction (AMI) in the contemporary era. Meanwhile, the incidence and prognosis of left ventricular aneurysm (LVA) in AMI patients remain ambiguous. The aim of the current study is to identify the predictor and long-term prognosis of LVA in patients with acute anterior myocardial infarction.

Variations in Energy Metabolism Precede Alterations in Cardiac Structure and Function in Hypertrophic Preconditioning.

Recent studies have unveiled that myocardial hypertrophic preconditioning (HP), which is produced by de-banding (De-TAC) of short-term transverse aortic constriction (TAC), protects the heart against hypertrophic responses caused by subsequent re-constriction (Re-TAC) in mice. Although cardiac substrate metabolism is impaired in heart failure, it remains unclear about the role of HP-driven energetics in the development of cardiac hypertrophy. Here, we investigated energy metabolism, cardiac hypertrophy, and function following variational loading conditions, as well as their relationships in HP.

Left ventricular response in the transition from hypertrophy to failure recapitulates distinct roles of Akt, β-arrestin-2, and CaMKII in mice with aortic regurgitation.

Background: Although aortic regurgitation (AR) is a clinically important condition that is becoming increasingly common, few relevant murine models and mechanistic studies exist for this condition. In this study, we attempted to delineate the pathological and molecular changes and address the roles of some potentially relevant molecules in an animal model of surgically induced AR.

Methods: AR was induced by puncturing the aortic valve leaflets in C57BL/6J mice under echocardiographic guidance.

Platelet function testing guided antiplatelet therapy reduces cardiovascular events in Chinese patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: The PATROL study.

Background: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor has become the standard of care to reduce thrombotic events in patients with acute coronary syndrome or after percutaneous coronary intervention (PCI). The role of routine platelet function testing (PFT) in patients treated with DAPT after PCI remains controversial and evidence of PFT-guided antiplatelet therapy for patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI is limited.

Methods: We analyzed 1,353 consecutive STEMI patients undergoing primary PCI.

Co-loading antioxidant N-acetylcysteine attenuates cytotoxicity of iron oxide nanoparticles in hypoxia/reoxygenation cardiomyocytes.

Purpose: Myocardial delivery of magnetic iron oxide nanoparticles (MNPs) might produce iron overload-induced myocardial injury, and the oxidative stress was regarded as the main mechanism. Therefore, we speculated antioxidant modification might be a reasonable strategy to mitigate the toxicity of MNPs.

Methods And Results: Antioxidant N-acetylcysteine (NAC) was loaded into magnetic mesoporous silica coated FeO nanoparticles.

Predictors and prognosis of left ventricular thrombus in post-myocardial infarction patients with left ventricular dysfunction after percutaneous coronary intervention.

Background: We aimed to investigate the predictors and prognosis of left ventricular thrombus (LVT) in patients admitted for post-myocardial infarction (MI) and left ventricular dysfunction after contemporary percutaneous coronary intervention (PCI).

Methods: We prospectively enrolled 267 consecutive post-MI patients with left ventricular ejection fraction (LVEF) <0.45 based on the Shanghai East Hospital PCI database since 2012.

HSF1 deficiency accelerates the transition from pressure overload-induced cardiac hypertrophy to heart failure through endothelial miR-195a-3p-mediated impairment of cardiac angiogenesis.

Heat shock transcription factor 1 (HSF1) deficiency aggravates cardiac remodeling under pressure overload. However, the mechanism is still unknown. Here we employed microRNA array analysis of the heart tissue of HSF1-knockout (KO) mice to investigate the potential roles of microRNAs in pressure overload-induced cardiac remodeling under HSF-1 deficiency, and the profiles of 478 microRNAs expressed in the heart tissues of adult HSF1-KO mice were determined.

Differential cardiac hypertrophy and signaling pathways in pressure versus volume overload.

Mechanical overload can be classified into pressure overload and volume overload, causing concentric and eccentric cardiac hypertrophy, respectively. Here, we aimed to differentiate the load-mediated signaling pathways involved in pressure versus volume overload cardiac hypertrophy. Pressure or volume overload was imposed on C57BL/6J mice by transverse aortic constriction (TAC) or aortic regurgitation (AR), respectively.

Ultrasound biomicroscopy validation of a murine model of cardiac hypertrophic preconditioning: comparison with a hemodynamic assessment.

In mice, myocardial hypertrophic preconditioning (HP), which is produced by the removal of short-term transverse aortic constriction (TAC), was recently reported to render the heart resistant to hypertrophic responses induced by subsequent reconstriction (Re-TAC). However, there is no efficient noninvasive method for ensuring that the repeated aortic manipulations were successfully performed. We previously demonstrated that ultrasound biomicroscopy (UBM) is a noninvasive and effective approach for predicting TAC success.

Characterization of coronary flow reserve and left ventricular remodeling in a mouse model of chronic aortic regurgitation with carvedilol intervention.

Objectives: We hypothesized that left ventricular (LV) remodeling might be exaggerated by an impaired coronary flow reserve in mice with chronic severe aortic regurgitation, and carvedilol, a β-adrenoceptor blocker, could regress the course.

Methods: Severe aortic regurgitation was induced by retrograde puncture of the aortic valve leaflets under sonographic guidance in 12-week-old male C57BL/6J mice. Four weeks after regurgitation, the mice were treated with carvedilol (30 mg/kg/d) or not treated (control).

Aliskiren ameliorates pressure overload-induced heart hypertrophy and fibrosis in mice.

Aim: Aliskiren (ALK) is a renin inhibitor that has been used in the treatment of hypertension. The aim of this study was to determine whether ALK could ameliorate pressure overload-induced heart hypertrophy and fibrosis, and to elucidate the mechanisms of action.

Methods: Transverse aortic constriction (TAC) was performed in mice to induce heart pressure overload.

Insights into the activation and inhibition of angiotensin II type 1 receptor in the mechanically loaded heart.

In the heart, mechanical load is a crucial regulator of myocardial structure and function; however, mechanical overload is a pathogenesis or comorbidity existing in a variety of heart diseases, such as hypertension, aortic regurgitation and myocardial infarction. Mechanical overload can be generally differentiated into 2 types, pressure overload (PO) and volume overload (VO), causing concentric and eccentric cardiac hypertrophy, respectively. The angiotensin II (AngII) type 1 receptor (AT1-R) is a 7 transmembrane G protein-coupled receptor that plays a critical role in load-induced cardiac hypertrophy.

Src is required for mechanical stretch-induced cardiomyocyte hypertrophy through angiotensin II type 1 receptor-dependent β-arrestin2 pathways.

Angiotensin II (AngII) type 1 receptor (AT1-R) can be activated by mechanical stress (MS) without the involvement of AngII during the development of cardiomyocyte hypertrophy, in which G protein-independent pathways are critically involved. Although β-arrestin2-biased signaling has been speculated, little is known about how AT1-R/β-arrestin2 leads to ERK1/2 activation. Here, we present a novel mechanism by which Src kinase mediates AT1-R/β-arrestin2-dependent ERK1/2 phosphorylation in response to MS.

The interplay between autophagy and apoptosis in the diabetic heart.

Diabetic cardiomyopathy is characterized by ventricular dysfunction that occurs in diabetic patients independent of coronary artery disease, hypertension, and any other cardiovascular diseases. Diabetic cardiomyopathy has become a major cause of diabetes-related mortality. Thus, an urgent need exists to clarify the mechanism of pathogenesis.

Olmesartan attenuates cardiac remodeling through DLL4/Notch1 pathway activation in pressure overload mice.

Background: Notch1 signaling controls the cardiac adaptation to stress. We therefore aimed to validate whether olmesartan, a widely used angiotensin II type 1 receptor blocker, ameliorates cardiac remodeling and dysfunction via delta-like ligand 4 (DLL4)/Notch1 pathway in mice with chronic pressure overload.

Methods: Cardiac pressure overload was produced by transverse aortic constriction (TAC).