LOX-1, the Common Therapeutic Target in Hypercholesterolemia: A New Perspective of Antiatherosclerotic Action of Aegeline
| Autor: | Ashok Kumar Srinivasan, Lakshmi Narasimhan Chakrapani, Abhilasha Singh, Periandavan Kalaiselvi |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Aging Article Subject Endothelium Atorvastatin Hypercholesterolemia 030204 cardiovascular system & hematology Pharmacology Diet High-Fat Biochemistry Cell Line Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo medicine Animals Humans Oil Red O Molecular Targeted Therapy Rats Wistar lcsh:QH573-671 Scavenger receptor Receptor lcsh:Cytology Chemistry Anticholesteremic Agents Macrophages Cell Biology General Medicine Atherosclerosis Scavenger Receptors Class E Amides Rats Lipoproteins LDL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Antihypercholesterolemic agent lipids (amino acids peptides and proteins) Research Article medicine.drug Lipoprotein |
| Zdroj: | Oxidative Medicine and Cellular Longevity, Vol 2019 (2019) Oxidative Medicine and Cellular Longevity |
| ISSN: | 1942-0994 1942-0900 |
| DOI: | 10.1155/2019/8285730 |
| Popis: | Background. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major receptor for oxidized low-density lipoprotein (Ox-LDL) in the aorta of aged rats. Ox-LDL initiates LOX-1 activation in the endothelium of lipid-accumulating sites of both animal and human subjects of hypercholesterolemia. Targeting LOX-1 may provide a novel diagnostic strategy towards hypercholesterolemia and vascular diseases.Hypothesis. This study was planned to address whether aegeline (AG) could bind to LOX-1 with a higher affinity and modulate the uptake of Ox-LDL in hypercholesterolemia.Study Design. Thirty-six Wistar rats were divided into six groups. The pathology group rats were fed with high-cholesterol diet (HCD) for 45 days, and the treatment group rats were fed with HCD and aegeline/atorvastatin (AV) for the last 30 days.In vivoandin vitroexperiments were carried out to assay the markers of atherosclerosis like Ox-LDL and LOX-1 levels. Histopathological examination was performed. Oil Red O staining was carried out in the IC-21 cell line. Docking studies were performed.Results. AG administration effectively brought down the lipid levels induced by HCD. The lowered levels of Ox-LDL and LOX-1 in AG-administered rats deem it to be a potent antihypercholesterolemic agent. Compared to AV, AG had a pronounced effect in downregulating the expression of lipids evidenced by Oil Red O staining. AG binds with LOX-1 at a higher affinity validated by docking.Conclusion. This study validates AG to be an effective stratagem in bringing down the lipid stress induced by HCD and can be deemed as an antihypercholesterolemic agent. |
| Databáze: | OpenAIRE |
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