Ferroptosis and Hydrogen Sulfide in Cardiovascular Disease.

Ferroptosis is an iron-dependent cell death, characterized by the accumulation of lipid-reactive oxygen species; various regulatory mechanisms influence the course of ferroptosis. The rapid increase in cardiovascular diseases (CVDs) is an extremely urgent problem. CVDs are characterized by the progressive deterioration of the heart and blood vessels, eventually leading to circulatory system disorder. Accumulating evidence, however, has highlighted crucial roles of ferroptosis in CVDs. Hydrogen sulfide plays a significant part in anti-oxidative stress, which may participate in the general mechanism of ferroptosis and regulate it by some signaling molecules. This review has primarily summarized the effects of hydrogen sulfide on ferroptosis and cardiovascular disease, especially the antioxidative stress, and would provide a more effective direction for the clinical study of CVDs.

Hippo: A New Hub for Atherosclerotic Disease.

Hippo, an evolutionarily conserved kinase cascade reaction in organisms, can respond to a set of signals, such as mechanical signals and cell metabolism, to maintain cell growth, differentiation, tissue/organ development, and homeostasis. In the past ten years, Hippo has controlled the development of tissues and organs by regulating the process of cell proliferation, especially in the field of cardiac regeneration after myocardial infarction. This suggests that Hippo signaling is closely linked to cardiovascular disease. Atherosclerosis is the most common disease of the cardiovascular system. It is characterised by chronic inflammation of the vascular wall, mainly involving dysfunction of endothelial cells, smooth muscle cells, and macrophages. Oxidized Low density lipoprotein (LDL) damages the barrier function of endothelial cells, which enter the middle membrane of the vascular wall, accelerate the formation of foam cells, and promote the occurrence and development of atherosclerosis. Autophagy is associated with the development of atherosclerosis. However, the mechanism of Hippo regulation of atherosclerosis has not meant to be clarified. In view of the pivotal role of this signaling pathway in maintaining cell growth, proliferation, and differentiation, the imbalance of Hippo is related to atherosclerosis and related diseases. In this review, we emphasized Hippo as a hub for regulating atherosclerosis and discussed its potential targets in pathophysiology, human diseases, and related pharmacology.

Hydrogen sulfide plays a potential alternative for the treatment of metabolic disorders of diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a cardiovascular complication that tends to occur in patients with diabetes, obesity, or insulin resistance, with a higher late mortality rate. Sustained hyperglycemia, increased free fatty acids, or insulin resistance induces metabolic disorders in cardiac tissues and cells, leading to myocardial fibrosis, left ventricular hypertrophy, diastolic and/or systolic dysfunction, and finally develop into congestive heart failure. The close connection between all signaling pathways and the complex pathogenesis of DCM cause difficulties in finding effective targets for the treatment of DCM. It reported that hydrogen sulfide (H2S) could regulate cell energy substrate metabolism, reduce insulin resistance, protect cardiomyocytes, and improve myocardial function by acting on related key proteins such as differentiation cluster 36 (CD36) and glucose transporter 4 (GLUT4). In this article, the relative mechanisms of H2S in alleviating metabolic disorders of DCM were reviewed, and how H2S can better prevent and treat DCM in clinical practice will be discussed.

Sestrin2 in atherosclerosis.

Atherosclerosis (AS) is the pathological basis of numerous lethal diseases, such as myocardial infarction, heart failure, and stroke. As we know, almost twenty million people worldwide die of the arterial diseases annually. Sestrin2 is a stress-inducing protein, which serves as a guardian by activating AMPK, inhibiting mTOR, and maintaining redox balance beneath various stress environments. A large number of studies show that Sestrin2 would shield the body from injury by stress. Moreover, it has been demonstrated that Sestrin2 is closely connected with AS. Here, this article reviewed the involvement of Sestrin2 in the pathogenesis of AS from four aspects: cellular mechanism, oxidative stress, inflammation, and lipid metabolism. Current evidence reveals that Sestrin2 is a novel target for the prevention and treatment of AS.

A promising field: regulating imbalance of EndMT in cardiovascular diseases.

Endothelial-mesenchymal transition (EndMT) is widely involved in the occurrence and development of cardiovascular diseases. Although there is no direct evidence, it is very promising as an effective target for the treatment of these diseases. Endothelial cells need to respond to the complex cardiovascular environment through EndMT, but sustained stimuli will cause the imbalance of EndMT. Blocking the signal transduction promoting EndMT is an effective method to control the imbalance of EndMT. In particular, we also discussed the potential role of endothelial cell apoptosis and autophagy in regulating the imbalance of EndMT. In addition, promoting mesenchymal-endothelial transformation (MEndT) is also a method to control the imbalance of EndMT. However, targeting EndMT to treat cardiovascular disease still faces many challenges. By reviewing the research progress of EndMT, we have put forward some insights and translated them into challenges and opportunities for new treatment strategies for cardiovascular diseases.

Effects of gut microbiota on atherosclerosis through hydrogen sulfide.

Cardiovascular diseases are the leading cause of death and morbidity worldwide. Atherosclerotic cardiovascular disease (ASCVD) is affected by both environmental and genetic factors. Microenvironmental disorders of the human gut flora are associated with a variety of health problems, not only gastrointestinal diseases, such as inflammatory bowel disease, but also extralintestinal organs. Hydrogen sulfide (H2S) is the third gas signaling molecule other than nitric oxide and carbon monoxide. In the cardiovascular system, H2S plays important roles in the regulation of blood pressure, angiogenesis, smooth muscle cell proliferation and apoptosis, anti-oxidative stress, cardiac functions. This review is aiming to explore the potential role of gut microbiota in the development of atherosclerosis through hydrogen sulfide production as a novel therapeutic direction for atherosclerosis.

The Role of Ubiquitin E3 Ligase in Atherosclerosis.

Atherosclerosis is a chronic inflammatory vascular disease. Atherosclerotic cardiovascular disease is the main cause of death in both developed and developing countries. Many pathophysiological factors, including abnormal cholesterol metabolism, vascular inflammatory response, endothelial dysfunction and vascular smooth muscle cell proliferation and apoptosis, contribute to the development of atherosclerosis and the molecular mechanisms underlying the development of atherosclerosis are not fully understood. Ubiquitination is a multistep post-translational protein modification that participates in many important cellular processes. Emerging evidence suggests that ubiquitination plays important roles in the pathogenesis of atherosclerosis in many ways, including regulation of vascular inflammation, endothelial cell and vascular smooth muscle cell function, lipid metabolism and atherosclerotic plaque stability. This review summarizes important contributions of various E3 ligases to the development of atherosclerosis. Targeting ubiquitin E3 ligases may provide a novel strategy for the prevention of the progression of atherosclerosis.

Hydrogen Sulfide Switch Phenomenon Regulating Autophagy in Cardiovascular Diseases.

Hydrogen sulfide (H2S), a novel gaseous signaling molecule, is a vital physiological signal in mammals. H2S protects the cardiovascular system via modulation of vasodilation, vascular remodeling, and inhibition of vascular calcification, and also has anti-atherosclerosis properties. Autophagy is a lysosomal-mediated intracellular degradation mechanism for excessive or abnormal proteins and lipids. The contribution of autophagy to normal and disease-state cell physiology is extremely complicated. Autophagy acts as a double-edged sword in the cardiovascular system. It can defend against damage to cells caused by environmental changes and it can also induce active cell death under certain conditions. In recent years, accumulating evidence indicates that H2S can up- or downregulate autophagy in many pathological processes, thereby switching from a harmful to a beneficial role. In this review, we summarize progress on understanding the mechanism by which H2S regulates autophagy in cardiovascular disease. We also discuss a H2S switch phenomenon that regulates autophagy and provides protection in cardiovascular diseases.

Tissue factor pathway inhibitor in atherosclerosis.

Tissue factor pathway inhibitor (TFPI) reduces the development of atherosclerosis by regulating tissue factor (TF) mediated coagulation pathway. In this review, we focus on recent findings on the inhibitory effects of TFPI on endothelial cell activation, vascular smooth muscle cell (VSMC) proliferation and migration, inflammatory cell recruitment and extracellular matrix which are associated with the development of atherosclerosis. Meanwhile, we are also concerned about the impact of TFPI levels and genetic polymorphisms on clinical atherogenesis. This article aims to explain the mechanism in inhibiting the development of atherosclerosis and clinical effects of TFPI, and provide new ideas for the clinical researches and mechanism studies of atherothrombosis.