Roles of eNOS in atherosclerosis treatment

Hong, Fashui; Liang, Xiaoyu; Liu, Wei; Lv, Sha; He, Shan; Kuang, Haibin; Yang, Shu‐Long

doi:10.1007/s00011-019-01229-9

Cited by 72 publications

(51 citation statements)

References 57 publications

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“…As an important endothelium-derived relaxation factor, NO plays a role in cardiovascular protection and anti-AS function. Endothelial nitric oxide synthase (eNOS) disorder causes an abnormal production of NO, which may damage endothelial function and trigger AS (Hong et al, 2019). The present study revealed decreased levels of NO in AS animals upon treatment with MTZ, which is in accordance with previous findings.…”

Section: Discussionmentioning

confidence: 99%

Carbonic Anhydrase 1-Mediated Calcification Is Associated With Atherosclerosis, and Methazolamide Alleviates Its Pathogenesis

et al. 2019

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Vascular calcification is an important pathogenic process in atherosclerosis (AS); however, its immediate cause is unknown. Our previous study demonstrated that carbonic anhydrase 1 (CA1) stimulates ossification and calcification in ankylosing spondylitis and breast cancer. The current study investigated whether CA1 plays an important role in AS calcification and whether the CA inhibitor methazolamide (MTZ) has a therapeutic effect on AS. We successfully established an AS model by administration of a high-fat diet to apolipoprotein E (ApoE −/− ) mice. The treated animals had significantly increased serum levels of high-density lipoprotein cholesterol (HDL-c) and nitric oxide (NO) and decreased serum concentrations of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), interleukin (IL-6), interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α), chemokine (C-X-C motif) ligand 1/keratinocyte-derived chemokine (CXCL1/KC), and C-C motif chemokine ligand 2 (CCL2)/monocyte chemoattractant protein 1 (MCP-1). The treated mice also had reduced AS plaque areas and fat accumulation, with no clear calcium deposition in the intima of the blood vessels. CA1 expression was significantly increased in the aortic lesions, particularly in calcified regions, but the expression was dramatically lower in the mice that received MTZ treatment or MTZ preventive treatment. CA1 was also highly expressed in human AS tissues and in rat vascular smooth muscle cells (VSMCs) with β-glycerophosphate (㒐β-GP)-induced calcification. Acetazolamide (AZ), a CA inhibitor with a chemical structure similar to MTZ, markedly suppressed calcification and reduced CA1, IL-6, IFN-γ, GM-CSF, and TNF-α expression in cultured VSMCs. Anti-CA1 small interfering ribonucleic acid (siRNA) significantly suppressed calcification, cell proliferation, and migration, promoted apoptosis, and reduced IL-6, IFN-γ, GM-CSF, and TNF-α secretion in cultured VSMCs. These results demonstrated that CA1 expression and CA1-mediated calcification are significantly associated with AS progression. MTZ significantly alleviated AS and suppressed CA1 expression and proinflammatory cytokine secretion, indicating the potential use of this drug for AS treatment.

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Section: Discussionmentioning

confidence: 99%

Carbonic Anhydrase 1-Mediated Calcification Is Associated With Atherosclerosis, and Methazolamide Alleviates Its Pathogenesis

et al. 2019

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“…This process, together with imbalanced calcium homeostasis, leads to decreased mitochondrial function and increased levels of NADPH and reactive oxygen species (ROS) in ECs under the pathological conditions of atherosclerosis [ 44 – 46 ]. Studies have indicated that NADPH and ROS inhibit the nitric oxide (NO) production and activity of endothelial nitric oxide synthase (eNOS), causing enhanced oxidative stress and vascular endothelial dysfunction [ 47 – 49 ]. Under ER stress, cytosolic Ca 2+ overload activated the inactive proenzyme procaspase-12 to form caspase-12 in the ER membrane of ECs; caspase-3 and apoptosis were eventually activated in these cells along with calpain-mediated caspase-9 activation [ 25 ].…”

Section: Proatherogenic Effects Of Er Stress In Different Cell Typmentioning

confidence: 99%

Role of Endoplasmic Reticulum Stress in Atherosclerosis and Its Potential as a Therapeutic Target

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Endoplasmic reticulum (ER) stress is closely associated with atherosclerosis and related cardiovascular diseases (CVDs). It occurs due to various pathological factors that interfere with ER homeostasis, resulting in the accumulation of unfolded or misfolded proteins in the ER lumen, thereby causing ER dysfunction. Here, we discuss the role of ER stress in different types of cells in atherosclerotic lesions. This discussion includes the activation of apoptotic and inflammatory pathways induced by prolonged ER stress, especially in advanced lesional macrophages and endothelial cells (ECs), as well as common atherosclerosis-related ER stressors in different lesional cells, which all contribute to the clinical progression of atherosclerosis. In view of the important role of ER stress and the unfolded protein response (UPR) signaling pathways in atherosclerosis and CVDs, targeting these processes to reduce ER stress may be a novel therapeutic strategy.

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“…NO produced by L-Arg possesses anti-atherogenic properties and plays a role in cardiovascular protection. However, in the pathological state, eNOS overactivation causes over-production of NO, leading to the development of atherosclerosis and damage of ECs (140). Modern therapies used to treat atherosclerosis often work to increase the bioavailability of NO in the vascular endothelium.…”

Section: Role Of L-arg In Atherosclerosismentioning

confidence: 99%

Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes

et al. 2020

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Cardiovascular disease is the leading global health concern and responsible for more deaths worldwide than any other type of disorder. Atherosclerosis is a chronic inflammatory disease in the arterial wall, which underpins several types of cardiovascular disease. It has emerged that a strong relationship exists between alterations in amino acid (AA) metabolism and the development of atherosclerosis. Recent studies have reported positive correlations between levels of branched-chain amino acids (BCAAs) such as leucine, valine, and isoleucine in plasma and the occurrence of metabolic disturbances. Elevated serum levels of BCAAs indicate a high cardiometabolic risk. Thus, BCAAs may also impact atherosclerosis prevention and offer a novel therapeutic strategy for specific individuals at risk of coronary events. The metabolism of AAs, such as L-arginine, homoarginine, and L-tryptophan, is recognized as a critical regulator of vascular homeostasis. Dietary intake of homoarginine, taurine, and glycine can improve atherosclerosis by endothelium remodeling. Available data also suggest that the regulation of AA metabolism by indoleamine 2,3-dioxygenase (IDO) and arginases 1 and 2 are mediated through various immunological signals and that immunosuppressive AA metabolizing enzymes are promising therapeutic targets against atherosclerosis. Further clinical studies and basic studies that make use of animal models are required. Here we review recent data examining links between AA metabolism and the development of atherosclerosis.

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Roles of eNOS in atherosclerosis treatment

Cited by 72 publications

References 57 publications

Carbonic Anhydrase 1-Mediated Calcification Is Associated With Atherosclerosis, and Methazolamide Alleviates Its Pathogenesis

Carbonic Anhydrase 1-Mediated Calcification Is Associated With Atherosclerosis, and Methazolamide Alleviates Its Pathogenesis

Role of Endoplasmic Reticulum Stress in Atherosclerosis and Its Potential as a Therapeutic Target

Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes

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