Mitochondrial autophagy (or mitophagy) regulates the mitochondrial network and function to contribute to multiple cellular processes. The protective effect of homeostatic mitophagy in cardiovascular diseases (CVDs) has attracted increasing attention. FUN14 domain containing 1 (FUNDC1), an identified mitophagy receptor, plays an essential role in CVDs. Different expression levels of FUNDC1 and its phosphorylated state at different sites alleviate or exacerbate hypoxia and ischemia/reperfusion injury, cardiac hypertrophy, or metabolic damage through promotion or inhibition of mitophagy. In addition, FUNDC1 can be enriched at contact sites between mitochondria and the endoplasmic reticulum (ER), determining the formation of mitochondria-associated membranes (MAMs) that regulate cellular calcium (Ca2+) homeostasis and mitochondrial dynamics to prevent heart dysfunction. Moreover, FUNDC1 has also been involved in inflammatory cardiac diseases such as septic cardiomyopathy. In this review, we collect and summarize the evidence on the roles of FUNDC1 exclusively in various CVDs, describing its interactions with different cellular organelles, its involvement in multiple cellular processes, and its associated signaling pathways. FUNDC1 may become a promising therapeutic target for the prevention and management of various CVDs.
As a new member of the organic framework family, halogen-bonded organic frameworks (XOFs) have the potential to gas capture and vaporchromic behavior yet remains to be explored. Herein, a novel...
Background. After myocardial infarction, anti-inflammatory macrophages perform key homeostatic functions that facilitate cardiac recovery and remodeling. Several studies have shown that lactate may serve as a modifier that influences phenotype of macrophage. However, the therapeutic role of sodium lactate in myocardial infarction (MI) is unclear. Methods. MI was established by permanent ligation of the left anterior descending coronary artery followed by injection of saline or sodium lactate. Cardiac function was assessed by echocardiography. The cardiac fibrosis area was assessed by Masson trichrome staining. Macrophage phenotype was detected via qPCR, flow cytometry, and immunofluorescence. Signaling proteins were measured by Western blotting. Results. Sodium lactate treatment following MI improved cardiac performance, enhanced anti-inflammatory macrophage proportion, reduced cardiac myocytes apoptosis, and increased neovascularization. Flow-cytometric analysis results reported that sodium lactate repressed the number of the IL-6+, IL-12+, and TNF-α+ macrophages among LPS-stimulated bone marrow-derived macrophages (BMDMs) and increased the mRNA levels of Arg-1, YM1, TGF-β, and IL-10. Mechanistic studies revealed that sodium lactate enhanced the expression of P-STAT3. Furthermore, a STAT3 inhibitor eliminated sodium lactate-mediated promotion macrophage polarization. Conclusion. Sodium lactate facilitates anti-inflammatory M2 macrophage polarization and protects against MI by regulating P-STAT3.
MARCH5 is a critical regulator of mitochondrial dynamics, apoptosis and mitophagy. However, its role in cardiovascular system remains poorly understood. This study aimed to investigate the role of MARCH5 in endothelial cell (ECs) injury and the involvement of the Akt/eNOS signalling pathway in this process. Rat models of myocardial infarction (MI) and human cardiac microvascular endothelial cells (HCMECs) exposed to hypoxia (1% O2) were used in this study. MARCH5 expression was significantly reduced in ECs of MI hearts and ECs exposed to hypoxia. Hypoxia inhibited the proliferation, migration and tube formation of ECs, and these effects were aggravated by knockdown of MARCH5 but antagonized by overexpressed MARCH5. Overexpression of MARCH5 increased nitric oxide (NO) content, p‐eNOS and p‐Akt, while MARCH5 knockdown exerted the opposite effects. The protective effects mediated by MARCH5 overexpression on ECs could be inhibited by eNOS inhibitor L‐NAME and Akt inhibitor LY294002. In conclusion, these results indicated that MARCH5 acts as a protective factor in ischaemia/hypoxia‐induced ECs injury partially through Akt/eNOS pathway.
Objective: Freezing of gait (FOG) is a disabling complication in Parkinson's disease (PD). Yet, studies on a validated model for the onset of FOG based on longitudinal observation are absent. This study aims to develop a risk prediction model to predict the probability of future onset of FOG from a multicenter cohort of Chinese patients with PD.Methods: A total of 350 patients with PD without FOG were prospectively monitored for ~2 years. Demographic and clinical data were investigated. The multivariable logistic regression analysis was conducted to develop a risk prediction model for FOG.Results: Overall, FOG was observed in 132 patients (37.70%) during the study period. At baseline, longer disease duration [odds ratio (OR) = 1.214, p = 0.008], higher total levodopa equivalent daily dose (LEDD) (OR = 1.440, p < 0.001), and higher severity of depressive symptoms (OR = 1.907, p = 0.028) were the strongest predictors of future onset of FOG in the final multivariable model. The model performed well in the development dataset (with a C-statistic = 0.820, 95% CI: 0.771–0.865), showed acceptable discrimination and calibration in internal validation, and remained stable in 5-fold cross-validation.Conclusion: A new prediction model that quantifies the risk of future onset of FOG has been developed. It is based on clinical variables that are readily available in clinical practice and could serve as a small tool for risk counseling.
Reactive oxygen species (ROS) metabolism is essential for the homeostasis of cells. Appropriate production of ROS is an important signaling molecule, but excessive ROS production can damage cells. ROS and ROS-associated proteins can act as damage associated molecular pattern molecules (DAMPs) to activate the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in cardiovascular diseases. Previous studies have shown that there are connected sites, termed mitochondria-associated membranes (MAMs), between mitochondria and the endoplasmic reticulum. In cardiovascular disease progression, MAMs play multiple roles, the most important of which is the ability to mediate ROS generation, which further activates the NLPR3 inflammasome, exacerbating the progression of disease. In this review, the following topics will be covered: 1. Molecular structures on MAMs that can mediate ROS generation; 2. Specific mechanisms of molecule-mediated ROS generation and the molecules' roles in cardiovascular disease, 3. The effects of MAMs-mediated ROS on the NLRP3 inflammasome in cardiovascular disease. The purpose of this review is to provide a basis for subsequent clinical treatment development.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.