Although great advances have been made, the problem of irreversible myocardium loss due to the limited regeneration capacity of cardiomyocytes has not been fully solved. The morbidity and mortality of heart disease still remain high. There are many therapeutic strategies for treating heart disease, while low efficacy and high cost remain challenging. Abundant evidence has shown that both acute and chronic inflammations play a crucial role in heart regeneration and repair following injury. Macrophages, a primary component of inflammation, have attracted much attention in cardiac research in recent decades. The detailed mechanisms of the roles of macrophages in heart regeneration and repair are not completely understood, in part because of their complex subsets, various functions, and intercellular communications. The purpose of this review is to summarize the progress made in the understanding of macrophages, including recent reports on macrophage differentiation, polarization and function, and involvement in heart regeneration and repair. Also, we discuss progress in treatments, which may suggest directions for future research.

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Despite the great progress made in the treatment for cardiovascular diseases (CVDs), the morbidity and mortality of CVDs remains high due to the lack of effective treatment strategy. Inflammation is a central pathophysiological feature of the heart in response to both acute and chronic injury, while the molecular basis and underlying mechanisms remains obscure. Interleukin (IL)‐13, a pro‐inflammatory cytokine, has been known as a critical mediator in allergy and asthma. Recent studies appraise the role of IL‐13 in CVDs, revealing that IL‐13 is not only involved in more obvious cardiac inflammatory diseases such as myocarditis but also relevant to acute or chronic CVDs of other origins, such as myocardial infarction and heart failure. The goal of this review is to summarize the advancement in our knowledge of the regulations and functions of IL‐13 in CVDs and to discuss the possible mechanisms of IL‐13 involved in CVDs. We highlight that IL‐13 may be a promising target for immunotherapy in CVDs.

Background: Primary aldosteronism (PA) is a common cause of secondary hypertension and confers a higher risk of stroke. The treatment strategies of PA mainly include medical and adrenalectomy treatment, while there is still no solid conclusion on how these two different treatment strategies mitigate the detrimental effect of PA on stroke. Methods: PubMed, Embase, and Cochrane Library were searched for studies comparing stroke events in patients with PA receiving medical treatment versus adrenalectomy treatment published up to 19 March 2022, including patients with essential hypertension as a control group. We used either fixed or random effect models according to the heterogeneities. Sensitivity analysis was conducted by deleting each study one at a time. Results: We reviewed 201 articles, and three studies met the final criteria, including 3244 PA patients with medical treatment, 1611 PA patients with adrenalectomy treatment, and 20,568 EH patients. Patients with PA post adrenalectomy were observed with a significantly decreased risk of stroke compared to patients receiving medical treatment (OR: 0.57, 95% CI: 0.35–0.93, p = 0.03), and with no difference when compared to patients with essential hypertension. Patients with PA receiving medical treatment were still observed with higher stroke risks (OR: 1.88, 95% CI: 1.68–2.11, p < 0.00001) than patients with essential hypertension. Conclusion: PA is a critical modifiable risk factor for stroke. Adrenalectomy has a superior performance in the mitigation of stroke risks among patients with PA.

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Aims The incidence of calcific aortic valve disease (CAVD) has risen over the last decade and is expected to continue rising; however, pharmacological approaches have proven ineffective. In this study, we evaluated the role and underlying mechanisms of human antigen R (HuR)-mediated post-transcriptional regulation in CAVD. Methods and results We found that HuR was significantly upregulated in human calcified aortic valves and primary aortic valvular interstitial cells (VICs) following osteogenic stimulation. Subsequent functional studies revealed that HuR silencing ameliorated calcification both in vitro and in vivo. For the first time, we demonstrated that HuR directly interacted with the transcript of phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP4K2A), which mediates phosphatidylinositol signaling, facilitates autophagy, and act as an mRNA stabilizer. HuR positively modulated PIP4K2A expression at the post-transcriptional level, and consequently influenced the AKT/mTOR/ATG13 pathway to regulate autophagy and CAVD progression. Conclusion Our study provides new insights into the post-transcriptional regulatory role of HuR in modulating autophagy-positive factors to regulate the pathogenesis of CAVD. Our findings highlight the potential of HuR as an innovative therapeutic target in CAVD treatment. Translational Perspective As the incidence of CAVD has been rising over the past decade with only invasive, expensive, and risky interventions available, it is imperative to explore novel approaches to halt aortic valve calcification. Currently, regulation of CAVD pathogenesis is not fully understood. HuR, an RNA-binding protein, and autophagy are thought to play key roles in CAVD; however, the precise underlying mechanisms have not been elucidated. Therefore, we believe that the findings of this study are relevant to the field because they provide direct evidence of a critical role for HuR, hVIC phenotypic transition, and autophagy in CAVD and suggest a novel target for hindering CAVD progression.

Hereditary transthyretin cardiac amyloidosis (hATTR-CA) is a rare autosomal dominantly inherited disease caused by mutations in the transthyretin (TTR) gene. TTR mutations often cause the instability of transthyretin, production of misfolded proteins, and ultimately excessive deposition of insoluble amyloid fibrils in the myocardium, thereby leading to cardiac dysfunction. Herein, we report a novel transthyretin D39Y mutation in a Chinese family. We characterized the kinetic and thermodynamic stabilities of D39Y mutant TTR, revealing that TTR D39Y mutant was less stable than WT TTR and more stable than amyloidogenic mutation TTR L55P. Meanwhile, the only FDA approved drug Tafamidis showed satisfactory inhibitory effect toward ATTR amyloid formation and strong binding affinity in test tube revealed by isothermal titration calorimetry. Finally, we measured the well-folded tetrameric TTR concentration in patient’s and his descents’ blood serum using a previously reported UPLC-based assay. Notably, the tetramer concentrations gradually increased from symptomatic D39Y gene carrier father, to asymptomatic D39Y gene carrier daughter, and further to wild type daughter, suggesting the decrease in functional tetrameric TTR concentration may serve as an indicator for disease age of onset in D39Y gene carriers. The study described a Chinese family with hATTR-CA due to the TTR variant D39Y with its destabilizing effect in both kinetic and thermodynamic stabilities.

BackgroundLeft ventricular thrombus (LVT) is a serious complication in patients with left ventricular dysfunction. However, there is still a paucity of data on treatments and prognosis of patients with LVT. This study aims to evaluate the clinical characteristics of patients with LVT and to determine the impact of LVT on the incidence of major adverse cardiovascular events (MACEs) and all-cause mortality.MethodsFrom January 2010 to January 2020, 237 patients diagnosed with LVT at The Second Affiliated Hospital Zhejiang University School of Medicine in East China were retrospectively included. Clinical characteristics, treatments, MACEs, and bleeding events [thrombolysis in myocardial infarction (TIMI) I and II] were collected. MACE is determined as the composite of all-cause mortality, ischemic stroke, acute myocardial infarction (MI), and acute peripheral artery emboli.ResultsThe all-cause mortality rate was 28.3% (89.6% due to cardiovascular death), ischemic stroke 8.4%, MI 3%, peripheral artery emboli 1.7%, and bleeding events (TIMI I and II) 7.6% were found during a median follow-up of 736 days. Total LVT regression occurred in 152 patients (64.1%). Atrial fibrillation [hazard ratio (HR), 3.049; 95% confidence interval (95% CI) 1.264–7.355; p = 0.013], moderate and severe renal function injuries (HR, 2.097; 95% CI, 1.027–4.281; p = 0.042), and left ventricular ejection fraction (LVEF) ≤ 50% (HR, 2.243; 95% CI 1.090–4.615; p = 0.028) were independent risk factors for MACE, whereas the use of β-blocker (HR, 0.397; 95% CI 0.210–0.753; p = 0.005) was its protective factor. Age (HR, 1.021; 95% CI 1.002–1.040; p = 0.031), previous caronary artery bypass grafting (CABG; HR, 4.634; 95% CI 2.042–10.517; p &lt; 0.001), LVEF ≤ 50% (HR, 3.714; 95% CI 1.664–8.290; p = 0.001), and large thrombus area (HR, 1.071; 95% CI 1.019–1.126; p = 0.007) were independent risk factors for increasing all-cause mortality, whereas the use of β-blocker (HR, 0.410; 95% CI 0.237–0.708; p = 0.001) was protective factor.ConclusionThis study showed that atrial fibrillation, moderate and severe renal dysfunction, and LVEF ≤ 50% were independent risk factors for MACE; age, previous CABG, LVEF ≤ 50%, and large thrombus area were independent risk factors for all-cause mortality. It was found that the use of β-blockers could improve the prognosis of patient with LVT for the first time. It is recommended that clinicians could be more active in applying patient with LVT with anticoagulants.