scholarly journals Recombinant Hirudin Protects the Vasculature and Myocardium in Atherosclerotic Rats by Inhibiting the p38 MAPK/NF-κB Signaling Pathway

2021 ◽  
Author(s):  
Wenping Guo ◽  
Hongguang Jin ◽  
Yiqiang Wang ◽  
Yongsheng Huang ◽  
Xing Zhu ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Common Carotid Artery ◽  
Mapk Pathway ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Recombinant Hirudin

Abstract Recombinant hirudin (r-hirudin) has a good anticoagulant effect and also has a certain inhibitory effect on atherosclerosis (AS), however, its intrinsic mechanism of inhibiting AS is still unclear. In this study, we investigated the mechanism underlying the vascular and myocardial protective effects of r-hirudin in AS rats through animal experiments. A rat AS model was established by high-fat diet feeding combined with common carotid artery balloon injury. The model rats were given low, medium, or high doses of r-hirudin (0.05, 0.1, or 0.2 mg/kg/day), simvastatin tablets (1 mg/kg/day) and p38 mitogen-activated protein kinase (MAPK) pathway inhibitors (SB203580, 100 mg/kg/day) by gavage for 8 weeks. The results showed that in AS rats, r-hirudin significantly alleviated pathological changes in the common carotid artery and myocardial tissue; decreased serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein-cholesterol (LDL-C) levels; increased high-density lipoprotein-cholesterol (HDL-C) levels; decreased serum oxidized low-density lipoprotein (ox-LDL), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and endothelin (ET)-1 levels; increased nitric oxide (NO) levels; and decreased p38 MAPK, nuclear factor-kappa B (NF-κB), caspase-9, caspase-3 mRNA and protein expression. This study showed that r-hirudin may protect blood vessels and the myocardium in AS rats by adjusting blood lipid levels and inhibiting the p38 MAPK/NF-κB signaling pathway to exert anti-inflammatory and anti-apoptotic effects and protect the vascular endothelium.

scholarly journals Relationship between small dense low-density lipoprotein cholesterol with carotid plaque in Chinese individuals with abnormal carotid artery intima-media thickness

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fang Liu ◽  
Zheng Wang ◽  
Xia Cao ◽  
Yingxia Pan ◽  
Erqiang Zhang ◽  
...  
Keyword(s):  
Risk Factor ◽  
Carotid Artery ◽  
Carotid Plaque ◽  
Independent Risk Factor ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Intima Media Thickness ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Abstract Aim To investigate the relationship of small dense low-density lipoprotein cholesterol (sdLDL-C) to carotid artery intima-media thickness (CA-IMT) and carotid plaque (CAP) in Chinese general population, and to evaluate whether sdLDL-C could be an independent risk factor for individuals with subclinical atherosclerosis. Methods A total of 729 subjects were randomly collected from consecutive individuals from April 2019 to April 2020 for an annual health checkup. CA-IMT > 1.0 mm was defined as abnormal IMT. Plaque stability was measured by ultrasound examination based on the property of the echo. And sdLDL-C levels were detected by LipoPrint system. Multivariate logistic regression analysis was performed to identify factors associated with CA-IMT and carotid plaque. Results The abnormal IMT group had significantly higher sdLDL-C levels than control group (p < 0.0001). And sdLDL-C levels were significantly positively correlated with IMT value (r = 0.1396, p = 0.0021) and presence of carotid plaque (r = 0.14, p = 0.002) in the subjects with abnormal IMT. In addition, subjects with higher levels of sdLDL-C (r = 0.11, p = 0.035) tended to have unstable CAP. After adjustment for age, gender and blood glucose, sdLDL-C level was an independent risk factor of the presence of CAP (OR = 1.59, 95% CI: 1.02–1.83, p = 0.034) in subjects with abnormal IMT. Conclusion SdLDL-C is an independent risk factor of the occurrence of CAP in the Chinese subjects with abnormal IMT. Our findings provide supporting evidence that sdLDL-C might be an alternative way to predict CVD in early stage.

scholarly journals The Microbiota Promotes Arterial Thrombosis in Low-Density Lipoprotein Receptor-Deficient Mice

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Klytaimnistra Kiouptsi ◽  
Sven Jäckel ◽  
Giulia Pontarollo ◽  
Alexandra Grill ◽  
Marijke J. E. Kuijpers ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Gut Microbiota ◽  
Common Carotid Artery ◽  
Ex Vivo ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
The Common

ABSTRACT Atherosclerotic plaque development depends on chronic inflammation of the arterial wall. A dysbiotic gut microbiota can cause low-grade inflammation, and microbiota composition was linked to cardiovascular disease risk. However, the role of this environmental factor in atherothrombosis remains undefined. To analyze the impact of gut microbiota on atherothrombosis, we rederived low-density lipoprotein receptor-deficient (Ldlr−/−) mice as germfree (GF) and kept these mice for 16 weeks on an atherogenic high-fat Western diet (HFD) under GF isolator conditions and under conventionally raised specific-pathogen-free conditions (CONV-R). In spite of reduced diversity of the cecal gut microbiome, caused by atherogenic HFD, GF Ldlr−/− mice and CONV-R Ldlr−/− mice exhibited atherosclerotic lesions of comparable sizes in the common carotid artery. In contrast to HFD-fed mice, showing no difference in total cholesterol levels, CONV-R Ldlr−/− mice fed control diet (CD) had significantly reduced total plasma cholesterol, very-low-density lipoprotein (VLDL), and LDL levels compared with GF Ldlr−/− mice. Myeloid cell counts in blood as well as leukocyte adhesion to the vessel wall at the common carotid artery of GF Ldlr−/− mice on HFD were diminished compared to CONV-R Ldlr−/− controls. Plasma cytokine profiling revealed reduced levels of the proinflammatory chemokines CCL7 and CXCL1 in GF Ldlr−/− mice, whereas the T-cell-related interleukin 9 (IL-9) and IL-27 were elevated. In the atherothrombosis model of ultrasound-induced rupture of the common carotid artery plaque, thrombus area was significantly reduced in GF Ldlr−/− mice relative to CONV-R Ldlr−/− mice. Ex vivo, this atherothrombotic phenotype was explained by decreased adhesion-dependent platelet activation and thrombus growth of HFD-fed GF Ldlr−/− mice on type III collagen. IMPORTANCE Our results demonstrate a functional role for the commensal microbiota in atherothrombosis. In a ferric chloride injury model of the carotid artery, GF C57BL/6J mice had increased occlusion times compared to colonized controls. Interestingly, in late atherosclerosis, HFD-fed GF Ldlr−/− mice had reduced plaque rupture-induced thrombus growth in the carotid artery and diminished ex vivo thrombus formation under arterial flow conditions.

scholarly journals Statins Suppress Oxidized Low Density Lipoprotein-induced Macrophage Proliferation by Inactivation of the Small G Protein-p38 MAPK Pathway

2004 ◽  
Vol 280 (8) ◽  
pp. 6627-6633 ◽  
Author(s):  
Takafumi Senokuchi ◽  
Takeshi Matsumura ◽  
Masakazu Sakai ◽  
Miyuki Yano ◽  
Tetsuya Taguchi ◽  
...  
Keyword(s):  
G Protein ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Small G Protein ◽  
P38 Mapk Pathway
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