scholarly journals Protective Effects of Angong Niuhuang Pill on Early Atherosclerosis in ApoE-/- Mice by Reducing the Inflammatory Response

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Yushuang Chai ◽  
Zhen Yin ◽  
Qinghong Fan ◽  
Zhe Zhang ◽  
Kaihe Ye ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Chemokine Receptors ◽  
Vascular Inflammation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Protective Effects ◽  
Anti Inflammatory Cytokine ◽  
Early Atherosclerosis

Atherosclerosis (AS) is the primary cause of cardiocerebrovascular disease, and inflammation is responsible for the initiation of its pathogenesis. Therefore, targeting inflammatory pathways to prevent AS progression is an ideal strategy. Angong Niuhuang pill (ANP) is a well-known traditional Chinese medicine and has been widely used for thousands of years to treat central nervous system and cardiovascular diseases. In this study, we investigated the role of ANP in reducing inflammation during early AS, using a high-fat diet-induced ApoE−/− mouse model of AS. Compared to those with simvastatin, ANP had no significant effect on serum triglyceride, low-density lipoprotein, and high-density lipoprotein levels. However, it effectively inhibited splenic and vascular inflammation. This agent also reduced the Th17/CD4+T ratio and mRNA expression of IL-6 and increased the Treg/CD4+T ratio and mRNA expression of TGF-β1. Thus, ANP restored Th17/Treg homeostasis in the spleen. It also regulated pro- and anti-inflammatory cytokine expression in the aorta in a similar manner. Further, it downregulated the expression of chemokine receptors (CCR2, CXCR3), their ligands (MCP-1, MCP-2, and MCP-3), and cell adhesion molecules (VCAM-1, ICAM-1) in arterial vessels. These results indicate that ANP can ameliorate the development of early AS, mainly by reducing inflammation instead of acting as an antihyperlipidemic drug.

scholarly journals PCSK9 Imperceptibly Affects Chemokine Receptor Expression In Vitro and In Vivo

2021 ◽  
Vol 22 (23) ◽  
pp. 13026
Author(s):  
Sai Sahana Sundararaman ◽  
Linsey J. F. Peters ◽  
Sumra Nazir ◽  
Andrea Bonnin Marquez ◽  
Janneke E. Bouma ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Cardiovascular Health ◽  
Vascular Inflammation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Receptor Expression ◽  
Vascular Cells ◽  
Mediators Of Inflammation

Proprotein convertase subtilin/kexin type 9 (PCSK9) is a protease secreted mainly by hepatocytes and in lesser quantities by intestines, pancreas, and vascular cells. Over the years, this protease has gained importance in the field of cardiovascular biology due to its regulatory action on the low-density lipoprotein receptor (LDLR). However, recently, it has also been shown that PCSK9 acts independent of LDLR to cause vascular inflammation and increase the severity of several cardiovascular disorders. We hypothesized that PCSK9 affects the expression of chemokine receptors, major mediators of inflammation, to influence cardiovascular health. However, using overexpression of PCSK9 in murine models in vivo and PCSK9 stimulation of myeloid and vascular cells in vitro did not reveal influences of PCSK9 on the expression of certain chemokine receptors that are known to be involved in the development and progression of atherosclerosis and vascular inflammation. Hence, we conclude that the inflammatory effects of PCSK9 are not associated with the here investigated chemokine receptors and additional research is required to elucidate which mechanisms mediate PCSK9 effects independent of LDLR.

scholarly journals Effect of Bamboo Leaf Extract on Antioxidant Status and Cholesterol Metabolism in Broiler Chickens

Animals ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 699
Author(s):  
Mingming Shen ◽  
Zechen Xie ◽  
Minghui Jia ◽  
Anqi Li ◽  
Hongli Han ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Antioxidant Status ◽  
Leaf Extract ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Abdominal Fat ◽  
Control Group ◽  
Low Density

The objective of this study was to investigate the effects of dietary bamboo leaf extract (BLE) on antioxidant status and cholesterol metabolism in broilers. One-day-old male Arbor Acres (576) broilers were randomly divided into six groups. A control group was fed a basal diet, while five experimental groups were supplemented with 1.0, 2.0, 3.0, 4.0, and 5.0g BLE per kg feed in their basal diets. The result indicated that BLE supplementation linearly improved eviscerated yield and decreased abdominal fat (p < 0.05). A significant decrease of serum triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c) content was observed with BLE supplementation (p < 0.05). BLE supplementation linearly improved the total antioxidant capacity and catalase activity in both serum and liver (p < 0.05). Glutathione peroxidase was quadratically increased in serum and linearly increased in the liver with BLE supplementation (p < 0.05). The malonaldehyde content in liver showed a linear and quadratic decrease with BLE supplementation (p < 0.05). BLE supplementation up-regulated the mRNA expression of cholesterol 7- alpha hydroxylase and low-density lipoprotein receptor and downregulated 3-hydroxy3-methyl glutamates coenzyme A reductase mRNA expression in the liver. The antioxidant enzyme mRNA expressions were all up-regulated by BLE supplementation in the liver. In conclusion, supplemental BLE improved antioxidant status and cholesterol metabolism in broilers, which eventually led to a decrease of serum TG, LDL-c content, and abdominal fat deposition.

scholarly journals Dyslipidemia in Chinese Pancreatic Cancer Patients: A Two-Center Retrospective Study

2021 ◽  
Author(s):  
Feiyang Wang ◽  
Heshui Wu ◽  
Junming Xu
Keyword(s):  
Pancreatic Cancer ◽  
High Density Lipoprotein ◽  
Mrna Expression ◽  
Low Density Lipoprotein ◽  
Laboratory Data ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
High Density ◽  
Low Density ◽  
Tumor Patients

Abstract Background: Pancreatic cancer (PC) is one of the most aggressive and lethal malignancies in the world. High cholesterol intake may have a certain association with an elevated risk of PC, though dyslipidemia in PC patients has rarely been reported. In this study, we compared serum lipids levels between PC and non-PC tumor patients and assessed their prognostic value in PC. Methods: 271 patients treated at Wuhan Union Hospital from January 2012 to December 2016 and 204 individuals at Shanghai General Hospital from January 2018 to December 2019 were recruited. Their demographic parameters, laboratory data, pathological information, and clinical outcomes were extracted and analyzed. The mRNA expressions of related lipoprotein, low density lipoprotein receptor (LDLR) and high density lipoprotein binding protein (HDLBP), in PC tissues and paired noncancerous tissues and follow-up information were assessed based on the GEO database (GSE15471 and GSE62165) and TCGA database. Results: A total of 172 non-PC tumor patients and 260 PC patients were finally eligible for our analysis. PC patients exhibited higher levels of serum triglyceride, cholesterol, and low-density lipoprotein (LDL) and a lower serum high-density lipoprotein (HDL) level on admission versus the non-PC tumor group. In PC patients, LDLR mRNA expression was upregulated, and HDLBP mRNA expression was downregulated in cancerous tissues compared to these levels in paired noncancerous tissues. The survival analysis revealed that dyslipidemia had a non-significant association with a poor prognosis, but PC patients with a high LDLR level were at risk of poor survival. Conclusion: Dyslipidemia is detected in PC patients but has a non-significant relation to PC prognosis. However, LDLR may be a potential predictive marker for PC prognosis.

The Role of the Low-Density Lipoprotein Receptor-Related Protein (LRP) in the Plasma Clearance and Liver Uptake of Recombinant Single-chain Urokinase-type Plasminogen Activator in Rats

1997 ◽  
Vol 77 (04) ◽  
pp. 710-717 ◽  
Author(s):  
Marieke E van der Kaaden ◽  
Dingeman C Rijken ◽  
J Kar Kruijt ◽  
Theo J C van Berkel ◽  
Johan Kuiper
Keyword(s):  
Plasminogen Activator ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Single Chain ◽  
Liver Uptake ◽  
Type Plasminogen Activator ◽  
Parenchymal Liver ◽  
Urokinase Type Plasminogen Activator ◽  
Density Lipoprotein Receptor

SummaryUrokinase-type plasminogen activator (u-PA) is used as a thrombolytic agent in the treatment of acute myocardial infarction. In vitro, recombinant single-chain u-PA (rscu-PA) expressed in E.coli is recognized by the Low-Density Lipoprotein Receptor-related Protein (LRP) on rat parenchymal liver cells. In this study we investigated the role of LRP in the liver uptake and plasma clearance of rscu-PA in rats. A preinjection of the LRP inhibitor GST-RAP reduced the maximal liver uptake of 125I-rscu-PA at 5 min after injection from 50 to 30% of the injected dose and decreased the clearance of rscu-PA from 2.37 ml/min to 1.58 ml/min. Parenchymal, Kupffer and endothelial cells were responsible for 40, 50 and 10% of the liver uptake, respectively. The reduction in liver uptake of rscu-PA by the preinjection of GST-RAP was caused by a 91 % and 62% reduction in the uptake by parenchymal and Kupffer cells, respectively. In order to investigate the part of rscu-PA that accounted for the interaction with LRP, experiments were performed with a mutant of rscu-PA lacking residues 11-135 (= deltal25- rscu-PA). Deletion of residues 11-135 resulted in a 80% reduction in liver uptake and a 2.4 times slower clearance (0.97 ml/min). The parenchymal, Kupffer and endothelial cells were responsible for respectively 60, 33 and 7% of the liver uptake of 125I-deltal25-rscu-PA. Preinjection of GST-RAP completely reduced the liver uptake of delta 125-rscu-PA and reduced its clearance to 0.79 ml/min. Treatment of isolated Kupffer cells with PI-PLC reduced the binding of rscu-PA by 40%, suggesting the involvement of the urokinase-type Plasminogen Activator Receptor (u-PAR) in the recognition of rscu-PA. Our results demonstrate that in vivo LRP is responsible for more than 90% of the parenchymal liver cell mediated uptake of rscu-PA and for 60% of the Kupffer cell interaction. It is also suggested that u-PAR is involved in the Kupffer cell recognition of rscu-PA.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

scholarly journals Reduction of Vascular Inflammation, LDL-C, or Both for the Protection from Cardiovascular Events?

2018 ◽  
Vol 12 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Andromachi Reklou ◽  
Michael Doumas ◽  
Konstantinos Imprialos ◽  
Konstantinos Stavropoulos ◽  
Dimitris Patoulias ◽  
...  
Keyword(s):  
Vascular Inflammation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Myocardial Damage ◽  
Lipid Lowering ◽  
Human Antibody ◽  
Low Grade ◽  
Cvd Risk ◽  
Expensive Drug ◽  
Arterial Inflammation

Background: Low density lipoprotein cholesterol (LDL-C) and low grade arterial inflammation are key pathogenic factors for atherosclerosis and its manifestation, cardiovascular disease (CVD). Objective: In this narrative review we assessed if decreasing LDL-C levels or inflammation or both is more effective in reducing CVD events. Results: In the Scandinavian Simvastatin Survival Study (4S), all statin trials of the 90s’ and the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) the benefit came from the LDL-C reduction. In the GREak and Atorvastatin Coronary heart disease Evaluation (GREACE), the Treating to New Targets (TNT), and the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trials both mechanisms in combination produced significant benefits. In the Atorvastatin for Reduction of MYocardial Damage during Angioplasty (ARMYDA) trials and the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) with a human antibody targeting IL-1β with no lipid lowering effect, the reduction in arterial inflammation played the only beneficial role because there was no change in lipids levels. Conclusion: Both LDL-C and inflammation reduction are beneficial to the reduction of CVD risk. However, canakinumab is a very expensive drug that only induced a 15% reduction in CVD events, thus drastically reducing the possibility for it to be used in clinical practice. Besides, canakinumab is associated with increased infections, some fatal. A potent statin with anti-inflammatory effects is probably the best choice for the majority of those needing hypolipidaemic drug therapy.

scholarly journals Subclinical Hypothyroidism and Indices for Metabolic Syndrome in Japanese Women: One-Year Follow-Up Study

2013 ◽  
Vol 98 (8) ◽  
pp. 3280-3287 ◽  
Author(s):  
Yasuyo Nakajima ◽  
Masanobu Yamada ◽  
Masako Akuzawa ◽  
Sumiyasu Ishii ◽  
Yasuhiro Masamura ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Odds Ratio ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Free T4 ◽  
The Relationship

Context: Subclinical hypothyroidism (SCH) and metabolic syndrome (MetS) increase with age; however, their relationship remains unclear. Objective: Our objective was to investigate the relationship between SCH and indices of metabolic syndrome and follow up subjects for 1 year. Design: Cross-sectional and longitudinal follow-up studies of cases were collected from Takasaki Hidaka Hospital between 2003 and 2007. Participants: Overall, 11 498 participants of health checkups were analyzed. The mean age was 48 ± 9 years. Main Outcome Measures: The relationship between SCH and indices of MetS were examined. Results: Serum free T4 levels were lower in women than men in most of the age groups, and the prevalence of SCH, 6.3% in women vs 3.4% in men, increased with age, reaching 14.6% in 70-year-old women. Multivariate logistic-regression analyses revealed that waist circumference and the serum triglyceride and low-density lipoprotein-cholesterol levels were significantly higher in subjects with SCH than without among women. Reflecting these findings, the adjusted odds ratio of MetS in patients with SCH was higher than in the euthyroid subjects in women with an odds ratio of 2.7 (95% confidence interval 1.1–5.6; P = .017) but not in men. Furthermore, progression from euthyroid into SCH resulted in a significant increase in the serum triglyceride levels but not low-density lipoprotein-cholesterol in women. Conclusion: Japanese women exhibited a high prevalence of SCH associated with low free T4 levels. There was a strong association between SCH and several indices of metabolic syndrome in women. SCH may affect serum triglyceride levels and be a risk factor for metabolic syndrome.

Sign in / Sign up

Export Citation Format

Share Document