Background And Purpose: Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo.
Experimental Approach: Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo.
Key Results: Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (-31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (-70%) and secretion (-28%) by peritoneal macrophages.
Conclusions And Implications: Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403102 | PMC |
http://dx.doi.org/10.1111/bph.13067 | DOI Listing |
Eur J Pharmacol
January 2025
State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology, College of Pharmacy, and Department of Cardiology, the Second Affiliated Hospital, Harbin Medical University, Harbin 150081, China; State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, and Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin 150081, China; Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, Harbin 150081, China. Electronic address:
Hyperlipidemia is a major risk factor for hypertension, coronary heart disease, diabetes and stroke, triggering an intensified research efforts into its prevention and treatment. Tetrahydroberberrubine (THBru) is a derivative of berberine (BBR) that has been shown to have higher bioavailability and lower toxicity compared to its parent compound. However, its impact on hyperlipidemia has not been fully explored.
View Article and Find Full Text PDFPoult Sci
December 2024
Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Department of International Agricultural Technology & Institute of Green Bioscience and Technology, Seoul National University, Pyeongchang, Republic of Korea. Electronic address:
The tumor virus A receptor (TVA), a member of the low-density lipoprotein receptor (LDLR) family, serves as an entry receptor for Avian Leukosis Virus (ALV) subgroups A and K, as well as a receptor for vitamin B bound to transcobalamin. Naturally occurring genetic variants in the TVA gene determine susceptibility or resistance to ALV-A and -K, but the effects of these mutated TVA on vitamin B uptake have not been investigated systemically. We found four TVA variants comprising the wild type (TVA), a single nucleotide polymorphism variant (TVA), and two partial deletions in the splicing branch point region (TVA).
View Article and Find Full Text PDFPLoS One
January 2025
Division of Cell- and Neurobiology, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
Emerging evidence suggests that fusion of cancer cells with leucocytes, such as macrophages, plays a significant role in cancer metastasis and results in tumor hybrid cells that acquire resistance to chemo- and radiation therapy. However, the precise mechanisms behind the leukocyte-cancer cell fusion remain unclear. The present in vitro study explores the presence of fusion between the monocyte cell line (THP-1) and the breast cancer cell line (MCF-7) in relation to the expression of CD36 and phosphatidylserine with and without treatment of these cells with ionizing radiation.
View Article and Find Full Text PDFCurr Atheroscler Rep
January 2025
Carbohydrate and Lipid Metabolism Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
Purpose Of Review: Homozygous familial hypercholesterolaemia (HoFH) is characterized by marked elevation of low-density lipoprotein cholesterol (LDLC) and premature atherosclerotic cardiovascular disease. This is a review of novel pharmacological therapies to lower LDLC in patients with HoFH.
Recent Findings: Novel therapies can be broadly divided by whether their efficacy is dependent or independent of residual low-density lipoprotein receptor (LDLR) function.
Alzheimers Dement
December 2024
HuaShan Hospital, Fudan University, Shanghai, China, Shanghai, China.
Background: To investigate the physiological clearance of circulating Aβ by the liver and its role in the pathogenesis of Alzheimer's disease (AD).
Method: Immunostaining, near-infrared imaging, and flow cytometry were used to explore the physiological clearance of Aβ by the liver and the impact of aging on Aβ clearance. Liver-specific LRP-1 knockdown and functional LRP-1 minigene (mLRP-1) expression in mice with AD were used to explore the effects of hepatic Aβ clearance on AD pathogenesis and treatment.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!