scholarly journals Salusins: Potential Use as a Biomarker for Atherosclerotic Cardiovascular Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Kengo Sato ◽  
Rena Watanabe ◽  
Fumiko Itoh ◽  
Masayoshi Shichiri ◽  
Takuya Watanabe
Keyword(s):  
Cardiovascular Diseases ◽  
Vascular Tissue ◽  
Inflammatory Responses ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Human Macrophage ◽  
Central Administration ◽  
Macrophage Foam Cell ◽  
Atherosclerotic Cardiovascular Diseases

Human salusin-αand salusin-βare related peptides produced from prosalusin. Bolus injection of salusin-βinto rats induces more profound hypotension and bradycardia than salusin-α. Central administration of salusin-βincreases blood pressure via release of norepinephrine and arginine-vasopressin. Circulating levels of salusin-αand salusin-βare lower in patients with essential hypertension. Salusin-βexerts more potent mitogenic effects on human vascular smooth muscle cells (VSMCs) and fibroblasts than salusin-α. Salusin-βaccelerates inflammatory responses in human endothelial cells and monocyte-endothelial adhesion. Human macrophage foam cell formation is stimulated by salusin-βbut suppressed by salusin-α. Chronic salusin-βinfusion into apolipoprotein E-deficient mice enhances atherosclerotic lesions; salusin-αinfusion reduces lesions. Salusin-βis expressed in proliferative neointimal lesions of porcine coronary arteries after stenting. Salusin-αand salusin-βimmunoreactivity have been detected in human coronary atherosclerotic plaques, with dominance of salusin-βin macrophage foam cells, VSMCs, and fibroblasts. Circulating salusin-βlevels increase and salusin-αlevels decrease in patients with coronary artery disease. These findings suggest that salusin-βand salusin-αmay contribute to proatherogenesis and antiatherogenesis, respectively. Increased salusin-βand/or decreased salusin-αlevels in circulating blood and vascular tissue are closely linked with atherosclerosis. Salusin-αand salusin-βcould be candidate biomarkers and therapeutic targets for atherosclerotic cardiovascular diseases.

Inhibitory effects of vasostatin-1 against atherogenesis

2018 ◽  
Vol 132 (23) ◽  
pp. 2493-2507 ◽  
Author(s):  
Yuki Sato ◽  
Rena Watanabe ◽  
Nozomi Uchiyama ◽  
Nana Ozawa ◽  
Yui Takahashi ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Inflammatory Responses ◽  
Foam Cell ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Inhibitory Effects ◽  
Macrophage Foam Cell ◽  
Down Regulation ◽  
Atherosclerotic Lesions

Vasostatin-1, a chromogranin A (CgA)-derived peptide (76 amino acids), is known to suppress vasoconstriction and angiogenesis. A recent study has shown that vasostatin-1 suppresses the adhesion of human U937 monocytes to human endothelial cells (HECs) via adhesion molecule down-regulation. The present study evaluated the expression of vasostatin-1 in human atherosclerotic lesions and its effects on inflammatory responses in HECs and human THP-1 monocyte-derived macrophages, macrophage foam cell formation, migration and proliferation of human aortic smooth muscle cells (HASMCs) and extracellular matrix (ECM) production by HASMCs, and atherogenesis in apolipoprotein E-deficient (ApoE−/−) mice. Vasostatin-1 was expressed around Monckeberg’s medial calcific sclerosis in human radial arteries. Vasostatin-1 suppressed lipopolysaccharide (LPS)-induced up-regulation of monocyte chemotactic protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in HECs. Vasostatin-1 suppressed inflammatory M1 phenotype and LPS-induced interleukin-6 (IL-6) secretion via nuclear factor-κB (NF-κB) down-regulation in macrophages. Vasostatin-1 suppressed oxidized low-density lipoprotein (oxLDL)-induced foam cell formation associated with acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) and CD36 down-regulation and ATP-binding cassette transporter A1 (ABCA1) up-regulation in macrophages. In HASMCs, vasostatin-1 suppressed angiotensin II (AngII)-induced migration and collagen-3 and fibronectin expression via decreasing ERK1/2 and p38 phosphorylation, but increased elastin expression and matrix metalloproteinase (MMP)-2 and MMP-9 activities via increasing Akt and JNK phosphorylation. Vasostatin-1 did not affect the proliferation and apoptosis in HASMCs. Four-week infusion of vasostatin-1 suppressed the development of aortic atherosclerotic lesions with reductions in intra-plaque inflammation, macrophage infiltration, and SMC content, and plasma glucose level in ApoE−/− mice. These results indicate the inhibitory effects of vasostatin-1 against atherogenesis. The present study provided the first evidence that vasostatin-1 may serve as a novel therapeutic target for atherosclerosis.

scholarly journals Neutrophils as a Novel Target of Modified Low-Density Lipoproteins and an Accelerator of Cardiovascular Diseases

2020 ◽  
Vol 21 (21) ◽  
pp. 8312
Author(s):  
Takashi Obama ◽  
Hiroyuki Itabe
Keyword(s):  
Cardiovascular Diseases ◽  
Inflammatory Responses ◽  
Foam Cell ◽  
Vascular Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Oxidative Modification ◽  
Foam Cell Formation ◽  
Low Density

Neutrophil extracellular traps (NETs) significantly contribute to various pathophysiological conditions, including cardiovascular diseases. NET formation in the vasculature exhibits inflammatory and thrombogenic activities on the endothelium. NETs are induced by various stimulants such as exogenous damage-associated molecular patterns (DAMPs). Oxidatively modified low-density lipoprotein (oxLDL) has been physiologically defined as a subpopulation of LDL that comprises various oxidative modifications in the protein components and oxidized lipids, which could act as DAMPs. oxLDL has been recognized as a crucial initiator and accelerator of atherosclerosis through foam cell formation by macrophages; however, recent studies have demonstrated that oxLDL stimulates neutrophils to induce NET formation and enhance NET-mediated inflammatory responses in vascular endothelial cells, thereby suggesting that oxLDL may be involved in cardiovascular diseases through neutrophil activation. As NETs comprise myeloperoxidase and proteases, they have the potential to mediate oxidative modification of LDL. This review summarizes recent updates on the analysis of NETs, their implications for cardiovascular diseases, and prospects for a possible link between NET formation and oxidative modification of lipoproteins.

Impact of Salusin-α and -β on Human Macrophage Foam Cell Formation and Coronary Atherosclerosis

Circulation ◽  
2008 ◽  
Vol 117 (5) ◽  
pp. 638-648 ◽  
Author(s):  
Takuya Watanabe ◽  
Kae Nishio ◽  
Tomoko Kanome ◽  
Taka-aki Matsuyama ◽  
Shinji Koba ◽  
...  
Keyword(s):  
Coronary Atherosclerosis ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Human Macrophage ◽  
Macrophage Foam Cell

scholarly journals A Chlamydia pneumoniae Component That Induces Macrophage Foam Cell Formation Is Chlamydial Lipopolysaccharide

1998 ◽  
Vol 66 (11) ◽  
pp. 5067-5072 ◽  
Author(s):  
Murat V. Kalayoglu ◽  
Gerald I. Byrne
Keyword(s):  
Cholesteryl Ester ◽  
Chlamydia Pneumoniae ◽  
Elevated Temperatures ◽  
Foam Cell ◽  
Cell Formation ◽  
Disease Process ◽  
Foam Cell Formation ◽  
Human Macrophage ◽  
Macrophage Foam Cell ◽  
Cholesteryl Ester Accumulation

ABSTRACT Chlamydia pneumoniae infection is associated with atherosclerotic heart and vessel disease, but a causal relationship between this pathogen and the disease process has not been established. Recently, it was reported that C. pneumoniae induces human macrophage foam cell formation, a key event in early atheroma development, suggesting a role for the organism in atherogenesis. This study further examines C. pneumoniae-induced foam cell formation in the murine macrophage cell line RAW-264.7. Infected RAW cells accumulated cholesteryl esters when cultured in the presence of low-density lipoprotein in a manner similar to that described for human macrophages. Exposure of C. pneumoniae elementary bodies to periodate, but not elevated temperatures, inhibited cholesteryl ester accumulation, suggesting a role for chlamydial lipopolysaccharide (cLPS) in macrophage foam cell formation. Purified cLPS was found to be sufficient to induce cholesteryl ester accumulation and foam cell formation. Furthermore, the LPS antagonist lipid X inhibited C. pneumoniae and cLPS-induced lipid uptake. These data indicate that cLPS is a C. pneumoniae component that induces macrophage foam cell formation and suggest that infected macrophages chronically exposed to cLPS may accumulate excess cholesterol to contribute to atheroma development.

Abstract 644: CD36 is Essential to Increased Atherosclerosis Mediated by Oral Infection With Porphromonas gingivalis

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Maria Febbraio ◽  
Paul M Brown
Keyword(s):  
Periodontal Disease ◽  
Inflammatory Responses ◽  
Foam Cell ◽  
Cell Formation ◽  
Atherosclerotic Lesion ◽  
Lipid Lowering ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Tlr2 Expression ◽  
Macrophage Foam Cell

Epidemiological evidence strongly support a link between periodontal disease & cardiovascular disease, but the mechanism(s) remains poorly understood. Using the human periodontal disease associated bacteria, Porphyromonas gingivalis (Pg) as a model, we carried out studies in macrophages & low density lipoprotein receptor (LDLR) KO mice. Pg associated similarly with macrophages from wild type & CD36 KO mice, but there were differences in responses dependent on Toll-like receptor (TLR) 2. We observed decreased NFkB activation & IL1beta generation following Pg treatment in CD36 KO macrophages, despite similar levels of TLR2 expression. OxLDL strongly inhibited Pg mediated IL-1beta generation in a CD36 dependent manner. Macrophage foam cell formation as a result of incubation with oxLDL & PgLPS was increased in a CD36 dependent manner. LDLR KO & CD36/LDLR double KO mice were orally infected with Pg & fed a Western diet (12 weeks). There was a significant increase in the cemento-enamel junction of molars of infected compared with uninfected mice, demonstrating the validity of the model. Histological analysis showed inflammatory cell infiltrates in gums of infected mice after 12 weeks, supporting a chronic inflammatory process. Differences in plasma parameters & weight gain did not necessarily track with atherosclerosis burden, however blood neutrophils & cytokines were increased in infected LDLR KO mice compared with all other groups. Infected LDLR KO mice had significantly increased atherosclerotic lesion burden compared with uninfected LDLR KO mice, and all of the increased lesion was CD36-dependent. Our data suggest that atherosclerosis associated with periodontal disease is mediated by cellular inflammatory responses involving both CD36 & TLR2. Pg enhances oxLDL mediated foam cell formation in a CD36 dependent manner, and this may explain increased lesion burden. Generation of IL1beta, a key pro-atherogenic cytokine, is altered as a result of CD36 expression. Periodontal disease affects more than 20% of the population of the US/Canada, & is associated with increasing age, which is also a risk factor for atherosclerosis. Targeting CD36 may provide important supplemental therapy to current lipid lowering strategies to reduce atherosclerosis.

scholarly journals Glucose-Dependent Insulinotropic Polypeptide Suppresses Foam Cell Formation of Macrophages through Inhibition of the Cyclin-Dependent Kinase 5-CD36 Pathway

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 832
Author(s):  
Michishige Terasaki ◽  
Hironori Yashima ◽  
Yusaku Mori ◽  
Tomomi Saito ◽  
Yoshie Shiraga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
U937 Cells ◽  
Cyclin Dependent Kinase ◽  
Macrophage Foam Cell ◽  
Cyclin Dependent Kinase 5 ◽  
Gip Receptor ◽  
Cd36 Gene

Glucose-dependent insulinotropic polypeptide (GIP) has been reported to have an atheroprotective property in animal models. However, the effect of GIP on macrophage foam cell formation, a crucial step of atherosclerosis, remains largely unknown. We investigated the effects of GIP on foam cell formation of, and CD36 expression in, macrophages extracted from GIP receptor-deficient (Gipr−/−) and Gipr+/+ mice and cultured human U937 macrophages by using an agonist for GIP receptor, [D-Ala2]GIP(1–42). Foam cell formation evaluated by esterification of free cholesterol to cholesteryl ester and CD36 gene expression in macrophages isolated from Gipr+/+ mice infused subcutaneously with [D-Ala2]GIP(1–42) were significantly suppressed compared with vehicle-treated mice, while these beneficial effects were not observed in macrophages isolated from Gipr−/− mice infused with [D-Ala2]GIP(1–42). When macrophages were isolated from Gipr+/+ and Gipr−/− mice, and then exposed to [D-Ala2]GIP(1–42), similar results were obtained. [D-Ala2]GIP(1–42) attenuated ox-LDL uptake of, and CD36 gene expression in, human U937 macrophages as well. Gene expression level of cyclin-dependent kinase 5 (Cdk5) was also suppressed by [D-Ala2]GIP(1–42) in U937 cells, which was corelated with that of CD36. A selective inhibitor of Cdk5, (R)-DRF053 mimicked the effects of [D-Ala2]GIP(1–42) in U937 cells. The present study suggests that GIP could inhibit foam cell formation of macrophages by suppressing the Cdk5-CD36 pathway via GIP receptor.

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