Targeting the forkhead box protein P1 pathway as a novel therapeutic approach for cardiovascular diseases.

Cardiovascular disease (CVD) is the leading cause of death worldwide and encompasses diverse diseases of the vasculature, myocardium, cardiac electrical circuit, and cardiac development. Forkhead box protein P1 (Foxp1) is a large multi-domain transcriptional regulator belonging to the Fox family with winged helix DNA-binding protein, which plays critical roles in cardiovascular homeostasis and disorders. The broad distribution of Foxp1 and alternative splicing isoforms implicate its distinct functions in diverse cardiac and vascular cells and tissue types. Foxp1 is essential for diverse biological processes and has been shown to regulate cellular proliferation, apoptosis, oxidative stress, fibrosis, angiogenesis, cardiovascular remodeling, and dysfunction. Notably, both loss-of-function and gain-of-function approaches have defined critical roles of Foxp1 in CVD. Genetic deletion of Foxp1 results in pathological cardiac remodeling, exacerbation of atherosclerotic lesion formation, prolonged occlusive thrombus formation, severe cardiac defects, and embryo death. In contrast, activation of Foxp1 performs a wide range of physiological effects, including cell growth, hypertrophy, differentiation, angiogenesis, and cardiac development. More importantly, Foxp1 exerts anti-inflammatory and anti-atherosclerotic effects in controlling coronary thrombus formation and myocardial infarction (MI). Thus, targeting for Foxp1 signaling has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of CVD, and an increased understanding of cardiovascular actions of the Foxp1 signaling will help to develop effective interventions. In this review, we focus on the diverse actions and underlying mechanisms of Foxp1 highlighting its roles in CVD, including heart failure, MI, atherosclerosis, congenital heart defects, and atrial fibrillation.

TRPC5 in cardiovascular diseases.

Cardiovascular diseases (CVD), especially acute myocardial infarction, are the leading cause of death, morbidity and disability across the world, affecting millions of people each year. Atherosclerosis (AS) is the major cause of CVD, and is a chronic inflammation involving different cell types and various molecular mechanisms. Ca2+ dynamics of endothelial cells (ECs) and smooth muscle cells (SMCs) exert a significant influence on many aspects of CVD. Transient receptor potential channel 5 (TRPC5) is a member of the transient receptor potential (TRP) channels, which consists of a large number of nonselective cation channels with variable degrees of Ca2+-permeability. As a Ca2+-permeable cation channel, Human TRPC5 is expressed in a number of cell types, including ECs and muscle cells, as well as lungs and kidneys. TRPC5 is involved in renal, tumorous, neuronal and vascular diseases. In recent years, the roles of TRPC5 in CVD have been widely implicated in various disorders, such as AS, cardiac hypertrophy and blood pressure regulation. The TRPC5 mechanism of action may be associated with regulation of calcium homeostasis, oxidative stress and apoptosis. In this review, we highlight the significant roles of TRPC5 in the heart, and evaluate the potential of therapeutics targets which block TRPC5 for the treatment of CVD and related diseases.

Plasma levels of Elabela are associated with coronary angiographic severity in patients with acute coronary syndrome.

BACKGROUND: Elabela (ELA) was newly discovered as a novel endogenous ligand of the apelin receptor (APJ) which has demonstrated to be crucial for cardiovascular disease such as myocardial infarction, hypertension and heart failure. Previous experiments have revealed that ELA reduced arterial pressure and exerted positive inotropic effects on the heart. However, the role of plasma ELA levels in patients with acute coronary syndrome (ACS) and its relationship with severity of coronary arteries have not been investigated. METHODS: Two hundred and one subjects who were hospitalized for chest pain and underwent coronary angiography were recruited in this study. One hundred and seventy five patients were diagnosed with ACS and twenty-six subjects with negative coronary angiography were included in the control group. Plasma ELA levels, routine blood test, blood lipid, liver and kidney functions were measured. The number of coronary arteries and SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score of coronary lesions were used to evaluate the extent of coronary artery stenosis. RESULTS: ELA in patients with ACS was significantly higher than that in the control group (P < 0.01). There was no significant difference in plasma ELA levels among patients with single-, double- and triple-vessel diseases. However, in the generalized additive model (GAM), there was a threshold nonlinear correlation between the ELA levels and Syntax I score (P < 0.001). Plasma ELA levels were positively correlated with the Syntax I score when the ELA levels ranged from 63.47 to 85.49 ng/mL. There was no significant association between the plasma ELA levels and the extent of coronary artery stenosis when the ELA levels were less than 63.47 ng/mL or higher than 85.49 ng/mL. CONCLUSION: The present study demonstrates for the first time that plasma ELA levels are increased in patients with ACS. The rise in endogenous ELA levels was associated with severity of coronary stenosis and may be involved in the pathogenesis of ACS.

Sampled-Data-Based Consensus and $L_{2}$ -Gain Analysis for Heterogeneous Multiagent Systems.

This paper is concerned with the sampled-data-based consensus problem of heterogeneous multiagent systems under directed graph topology with communication failure. The heterogeneous multiagent system consists of first-order and second-order integrators. Consensus of the heterogeneous multiagent system may not be guaranteed if the communication failure always happens. However, if the frequency and the length of the communication failure satisfy certain conditions, consensus of the considered system can be reached. In particular, we introduce the concepts of communication failure frequency and communication failure length. Then, with the help of the switching technique and the Lyapunov stability theory, sufficient conditions are derived in terms of linear matrix inequalities, which guarantees that the heterogeneous multiagent system not only achieves consensus but also maintains a desired L2 -gain performance. A simulation example is given to show the effectiveness of the proposed method in this paper.

[Characteristics of SRAP marker in detecting polymorphism of cucumber genome].

When SRAP (Sequence-Related Amplified Polymorphism) marker was used in constructing genetic map and analyzing QTL for high temperature resistance in cucumber (Cucumis sativus L.), it exhibited certain characteristics in detecting genomic polymorphism. When each forward primer was combined with different reverse primers, the number of primer combinations that produced polymorphism ranged from five to eight. When each reverse primer was in combination with different forward primers, the number of polymorphic primer combinations ranged from two to eleven. The reverse primers SA4 or EM6 produced identical polymorphic bands when combined with all the forward primers tested. These bands might be amplified by the reverse primers. The polymorphic bands amplified from OD3ME11 co-segregated in the F2 population. The utilization of these characteristics in our research was discussed.