Aminoacyl-tRNA synthetases (ARSs) are widely found in organisms, which can activate amino acids and make them bind to tRNA through ester bond to form the corresponding aminoyl-tRNA. The classic function of ARS is to provide raw materials for protein biosynthesis. Recently, emerging evidence demonstrates that ARSs play critical roles in controlling inflammation, immune responses, and tumorigenesis as well as other important physiological and pathological processes. With the recent development of genome and exon sequencing technology, as well as the discovery of new clinical cases, ARSs have been reported to be closely associated with a variety of cardiovascular diseases (CVDs), particularly angiogenesis and cardiomyopathy. Intriguingly, aminoacylation was newly identified and reported to modify substrate proteins, thereby regulating protein activity and functions. Sensing the availability of intracellular amino acids is closely related to the regulation of a variety of cell physiology. In this review, we summarize the research progress on the mechanism of CVDs caused by abnormal ARS function and introduce the clinical phenotypes and characteristics of CVDs related to ARS dysfunction. We also highlight the potential roles of aminoacylation in CVDs. Finally, we discuss some of the limitations and challenges of present research. The current findings suggest the significant roles of ARSs involved in the progress of CVDs, which present the potential clinical values as novel diagnostic and therapeutic targets in CVD treatment.

Cardiovascular disease (CVD) is one of the most threatening diseases to human health and life, and the number of patients is increasing year by year. Thus, it is of great significance to study the pathogenesis, prevention and treatment of CVDs. The occurrence and development of CVDs involve dynamic, complex and delicate intracellular processes and the pathogenesis is not entirely clear. In contrast to genetic mutations, most of the protein post-translational modifications (PTMs) are reversible, and can affect the activity, stability, subcellular localization, protein-protein interaction etc., of the substrate targets, emerging as key mediators of a number of CVD progression. Under pathological conditions, the PTMs undergo aberrant balances which cause changes of the substrate target proteins in expression level, localization and capacity to activate downstream signaling pathways. Therefore, new approaches can be created aiming to correct the abnormal PTM alterations in treating CVDs. This review summarizes some of the more recent advances in PTMs, focusing on SUMOylation, neddylation, succinylation, and prenylation, and the effect of these modifications on cardiovascular function and progression, which may provide potential targets for future therapeutics.

Introduction: With the rapid development of sequencing technologies, several long non-coding RNAs (lncRNAs) have been identified; among which many are significant players in cardiac physiology and pathology. Doxorubicin (Dox), a commonly used anticancer agent, in the long-term can induce cardiotoxicity, limiting its clinical use. Despite the multiple signaling pathways involved in Dox cardiotoxicity, most of them ultimately lead to the activation of apoptosis, contributing to the progressive cardiomyocyte loss, and hence ensuring heart failure. Methods and Results: Microarray analysis showed that multiple lncRNAs were differentially expressed between control and doxorubicin-treated groups, denoting that lncRNAs may play a critical role in Dox cardiotoxicity. Functional enrichment analysis displayed that the differentially expressed genes are annotated to MAPK signaling and cardiac hypertrophic pathways. CMDL-1 is first characterized in rat cardiomyocytes and is the most significantly downregulated lncRNA after doxorubicin exposure. CMDL-1 is located upstream to the transient receptor potential cation channel, subfamily M, member 7 (Trpm-7), which can function as a kinase by phosphorylating itself or other substrates. Mechanistic analysis indicated that lentiviral overexpression of CMDL-1 decreased Dox-induced mitochondrial fission (MitoTracker Red CMXRos) and apoptosis (TUNEL and flow cytometry) in cardiomyocytes. Bioinformatic and experimental data showed that CMDL-1 could bind to Drp1. Overexpression of CMDL-1 promoted its association with Drp1, as well as with phosphorylated (p)-Drp1, evidenced by RNA immunoprecipitation analysis. However, overexpression of CMDL-1 couldn’t effectively reduce mitochondrial fission if Drp1 was minimally expressed by siDrp1. These findings suggest that CMDL-1 could prevent mitochondrial fission and apoptosis by impairing Drp1 phosphorylation. Conclusions: Collectively, we demonstrated that a novel lncRNA CMDL-1 could play a protective role in cardiac injury and could be a potential therapeutic target in Dox cardiotoxicity. Our study is additional evidence of the less appreciated mechanism of lncRNAs, modulating the phosphorylation status of its interacting proteins.

Accumulation of reactive oxygen species is a common phenomenon in cardiac stress conditions, for instance, coronary artery disease, aging-related cardiovascular abnormalities, and exposure to cardiac stressors such as hydrogen peroxide (H2O2). Mitochondrial protein 18 (Mtp18) is a novel mitochondrial inner membrane protein, shown to involve in the regulation of mitochondrial dynamics. Although Mtp18 is abundant in cardiac muscles, its role in cardiac apoptosis remains elusive. The present study aimed to detect the role of Mtp18 in H2O2-induced mitochondrial fission and apoptosis in cardiomyocytes. We studied the effect of Mtp18 in cardiomyocytes by modulating its expression with lentiviral construct of Mtp18-shRNA and Mtp18 c-DNA, respectively. We then analyzed mitochondrial morphological dynamics with MitoTracker Red staining; apoptosis with terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) and cell death detection assays; and protein expression with immunoblotting. Here, we observed that Mtp18 could regulate oxidative stress- mediated mitochondrial fission and apoptosis in cardiac myocytes. Mechanistically, we found that Mtp8 induced mitochondrial fission and apoptosis by enhancing dynamin-related protein 1 (Drp1) accumulation. Conversely, knockdown of Mtp18 interfered with Drp1-associated mitochondrial fission and subsequent activation of apoptosis in both HL-1 cells and primary cardiomyocytes. However, overexpression of Mtp18 alone was not sufficient to execute apoptosis when Drp1 was minimally expressed, suggesting that Mtp18 and Drp1 are interdependent in apoptotic cascade. Together, these data highlight the role of Mtp18 in cardiac apoptosis and provide a novel therapeutic insight to minimize cardiomyocyte loss via targetting mitochondrial dynamics.

Long non-coding RNAs (lncRNAs) have gained more attention in recent years as a potential new regulator of nearly all biological regulation. LncRNAs are over 200 nucleotides in length, and it can interact with other non-coding RNAs or specific proteins to influence the gene expression. Cardiomyocyte apoptosis is associated with cardiovascular diseases. Accumulating studies have uncovered novel lncRNAs-mediated regulation of cardiovascular diseases; however, the knowledge of the mechanisms by how to act is still limited. This review highlights the role of lncRNAs involved in cardiomyocyte apoptosis with a focus on the regulatory axis. These examples may provide helpful insights on how lncRNAs interfere with cardiomyocyte apoptosis.

Apoptosis plays a critical role in the development of myocardial infarction. Cardiomyocytes are enriched with mitochondria and excessive mitochondrial fission can trigger cellular apoptosis. Recently, the mitochondrial ubiquitin ligase (MITOL), localized in the mitochondrial outer membrane, was reported to play an important role in the regulation of mitochondrial dynamics and apoptosis. However, the underlying mechanism of its action remains uncertain. The present study was aimed at uncovering the role of MITOL in the regulation of cardiomyocyte apoptosis. Our results showed that MITOL expression was up‐regulated in cardiomyocytes in response to apoptotic stimulation. Mitochondrial ubiquitin ligase overexpression blocked dynamin‐related protein 1 accumulation in the mitochondria, and attenuated the mitochondrial fission induced by hydrogen peroxide. Conversely, MITOL knockdown sensitized cardiomyocytes to undergo mitochondrial fission, resulting in subsequent apoptosis. These findings suggest that MITOL plays a protective role against apoptosis in cardiomyocytes, and may serve as a potential therapeutic target for apoptosis‐related cardiac diseases.

Chinese Maonan nationality is an isolated minority with a population of 107,166 in 2010. They mainly reside in several townships of Huanjiang Maonan Autonomous County in the Northwestern of Guangxi, China. The prevalence and epidemiological characters of dyslipidemia in this ethnic group have not been studied previously. The objective of the present study was to assess the difference in serum lipid levels, the prevalence of dyslipidemia and the risk factors in the Maonan and Han populations. A cross-sectional study of dyslipidemia was conducted in 1332 unrelated subjects of Maonan and 1344 participants of Han ethnic groups. Information on epidemiological survey was collected with standardized questionnaires. Anthropometric and biochemical data were obtained. Serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels were higher but high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) A1 and ApoB levels were lower in Maonan than in Han (P < 0.01-0.001). The prevalence of hypercholesterolemia (40.09% vs. 33.93%, P < 0.01), hypertriacylglycerolemia (29.13% vs. 16.52%, P < 0.001) and hyperlipidemia (51.95% vs. 41.07%, P < 0.001) was higher in Maonan than in Han. The anormal rates of HDL-C, LDL-C, and ApoA1 were also higher but the anormal rate of ApoB was lower in Maonan than in Han (P < 0.001 for all). The effects of sex, age, body mass index (BMI), hypertension, alcohol consumption, and cigarette smoking on serum lipid levels and the prevalence of dyslipidemia were different between the Maonan and Han populations. The prevalence of hyperlipidemia was positively correlated with BMI, hypertension and the intakes of total energy and total fat in Maonan (P < 0.01 for all), whereas it was positively associated with BMI, and the intakes of total energy and total fat in Han (P < 0.01). The difference in the serum lipid levels and the prevalence of dyslipidemia between the two populations might result from the combined effects of different BMI, hypertension, diet, lifestyle, and genetic background.

The association of single nucleotide polymorphisms (SNPs) in the MLX interacting protein-like (MLXIPL), BUD13 homolog (BUD13) and zinc finger protein 259 (ZNF259) genes is inconsistent in diverse racial/ethnic groups. The present study was undertaken to detect the association of the MLXIPL (

This study aimed to detect the association between the MLX interacting protein-like (MLXIPL), BUD13 homolog (BUD13) and zinc finger protein 259 (ZNF259) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese Mulao and Han populations. Genotyping of 9 SNPs was performed in 825 Mulao and 781 Han participants. The genotype and allele frequencies of ZNF259 rs2075290 and rs964184 and BUD13 rs10790162 SNPs were different between the Mulao and Han populations (P < 0.001). The SNPs of ZNF259 rs2075290 and BUD13 rs10790162 were associated with serum total cholesterol levels; ZNF259 rs2075290 and rs964184, BUD13 rs10790162 and MLXIPL rs3812316 and rs13235543 were associated with triglyceride (TG); and MLXIPL rs35332062 was associated with apolipoprotein (Apo) A1 in the Mulaos (P < 0.006–0.001). However, in the Hans, the SNPs of ZNF259 rs2075290 and BUD13 rs10790162 were associated with serum TG levels; ZNF259 rs2075290 was associated with low-density lipoprotein cholesterol and the ApoA1/ApoB ratio (P < 0.006–0.001). Significant linkage disequilibria were noted among ZNF259 rs2075290 and rs964184 and BUD13 rs10790162 and between MLXIPL rs3812316 and rs13235543 (r2 > 0.05, P < 0.001). The haplotypes of A-C-G-A-C (rs2075290A-rs964184C-rs10790162G-rs17119975A-rs11556024C) and C-C-C-C (rs799161C-rs35332062C-rs3812316C-rs13235543C) accounted for over half of the % haplotype of each ethnic group.