Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Da Som Jeong Ji-Young Lee Hyo-Jeong Han Soo Min Ko Dong Hyun Lee Yerin Lee Young-Sik Park Byong-Cheol Shin Woo-Chan Son
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제29권 제2호, 179~189쪽, 전체 11쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2025.03.01

국문 초록

Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE-/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE–/– mice. This study highlights PA9RA's potential as a promising therapeutic agent foratherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.

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키워드

Apolipoproteins E Atherosclerosis Tretinoin