Pharmacological inhibition of MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) induces ferroptosis in vascular smooth muscle cells.

MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a human paracaspase protein with proteolytic activity via its caspase-like domain. The pharmacological inhibition of MALT1 by MI-2, a specific chemical inhibitor, diminishes the response of endothelial cells to inflammatory stimuli. However, it is largely unknown how MALT1 regulates the functions of vascular smooth muscle cells (SMCs).

Impact of Short-Term (+)-JQ1 Exposure on Mouse Aorta: Unanticipated Inhibition of Smooth Muscle Contractility.

(+)-JQ1, a specific chemical inhibitor of bromodomain and extraterminal (BET) family protein 4 (BRD4), has been reported to inhibit smooth muscle cell (SMC) proliferation and mouse neointima formation via BRD4 regulation and modulate endothelial nitric oxide synthase (eNOS) activity. This study aimed to investigate the effects of (+)-JQ1 on smooth muscle contractility and the underlying mechanisms. Using wire myography, we discovered that (+)-JQ1 inhibited contractile responses in mouse aortas with or without functional endothelium, reducing myosin light chain 20 (LC20) phosphorylation and relying on extracellular Ca.

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.

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.

PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Triggers Vascular Smooth Muscle Cell Senescence and Apoptosis: Implication of Its Direct Role in Degenerative Vascular Disease.

Objective: PCSK9 (proprotein convertase subtilisin/kexin type 9) plays a critical role in cholesterol metabolism via the PCSK9-LDLR (low-density lipoprotein receptor) axis in the liver; however, evidence indicates that PCSK9 directly contributes to the pathogenesis of various diseases through mechanisms independent of its LDL-cholesterol regulation. The objective of this study was to determine how PCSK9 directly acts on vascular smooth muscle cells (SMCs), contributing to degenerative vascular disease. Approach and Results: We first examined the effects of PCSK9 on cultured human aortic SMCs.

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.

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 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.

PCSK9: Associated with cardiac diseases and their risk factors?

PCSK9 plays a critical role in cholesterol metabolism via the PCSK9-LDLR axis. Liver-derived, circulating PCSK9 has become a novel drug target in lipid-lowering therapy. Accumulative evidence supports the possible association between PCSK9 and cardiac diseases and their risk factors.

Multifunctional RNase MCPIP1 and its Role in Cardiovascular Diseases.

Monocyte chemoattractant protein-1 induced protein 1 (MCPIP1), one of the MCPIP family members, is characterized by the presence of both C-x8-C-x5-C-x3-H (CCCH)- type zinc finger and PilT-N-terminal domains. As a potent regulator of innate immunity, MCPIP1 exerts anti-inflammatory effects through its ribonuclease (RNase) and deubiquitinating enzyme activities to degrade cytokine mRNAs and inhibit nuclear factor- kappa B (NF-κB), respectively. MCPIP1 is expressed not only in immune cells but also in many other cell types, including cardiomyocytes, vascular endothelial cells (ECs) and smooth muscle cells (SMCs).

Physiology and role of PCSK9 in vascular disease: Potential impact of localized PCSK9 in vascular wall.

Proprotein convertase subtilisin/kexin type-9 (PCSK9), a member of the proprotein convertase family, is an important drug target because of its crucial role in lipid metabolism. Emerging evidence suggests a direct role of localized PCSK9 in the pathogenesis of vascular diseases. With this in our consideration, we reviewed PCSK9 physiology with respect to recent development and major studies (clinical and experimental) on PCSK9 functionality in vascular disease.

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.

Hydrogen Sulfide Switch Phenomenon Regulating Autophagy in Cardiovascular Diseases.

Hydrogen sulfide (HS), a novel gaseous signaling molecule, is a vital physiological signal in mammals. HS 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.