Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice

Abstract

Background and aimsAtherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice.Methods and resultsMice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice.ConclusionsVitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.

Red Wine Grape Pomace Attenuates Atherosclerosis and Myocardial Damage and Increases Survival in Association with Improved Plasma Antioxidant Activity in a Murine Model of Lethal Ischemic Heart Disease

“…Body weights did not differ between groups during the dietary interventions (Supplemental Figure S1). HFC-Control diet-fed SR-B1 KO/ApoER61 h/h mice presented hypercholesterolemia after 7 and 14 days of diet consumption compared to baseline in accordance with previous observations from our group [28,29] (Figure 2A). Similar increases in total cholesterol levels were found for HFC-RWGP diet-fed mice.…”

“…SR-B1 KO/ApoER61 h/h mice rapidly respond to the challenge of an atherogenic diet with plaque formation both in the aortic root and coronary arteries, recapitulating many features of human ASCVD [20]. SR-B1 KO/ApoER61 h/h mice fed with HFC-Control diet readily developed plaques in highly vulnerable regions along the arterial tree, in agreement with previously published data [12,28,29,50]. Supplementation with RWGP significantly reduced atherosclerotic lesion development.…”

“…Polyphenols (α-tocopherol, gallic acid (GA), catechin, flavonols, and malvidin) are the main antioxidants present in RWGP [18]. Similar findings were previously published with a combined supplementation of vitamin C and E, both well-known antioxidants, in atherogenic diet-fed SR-B1 KO/ApoER61 h/h mice [29]. Recent studies have revealed that GA has beneficial effects against several cardiovascular diseases, specifically GA, which suppresses cardiac hypertrophic remodeling and heart failure [38].…”

The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway

“…In vivo studies have investigated the antiatherosclerotic effect of a combined vitamin C and vitamin E supplementation in mouse models of this pathology: vitamin C/vitamin E cocktail inhibited the development of fatty streak lesions in the LDLr -/mice [133] and limited aortic Vegf and Vegfr-2 expression in ApoE -/mice [134] compared to nontreated littermates. In a very recent study, in atherogenic diet-fed (scavenger receptor class B type 1) SR-B1 KO/ApoER61 h/h mice, a murine model of dyslipidemia, progressive atherosclerosis, CHD and premature ischemic death, 9 Oxidative Medicine and Cellular Longevity combined with administration of vitamins C and E reduced serum total cholesterol and triglyceride levels, improved HDL antioxidant function, and lowered serum TNF-α levels [135].…”

Investigation of Serum Paraoxonase 1 (PON1) Activities in Postprandial Lipemia

“…Ayrıca HDL, özellikle yapısında bulunan paraoksonaz-1 (PON1) enzimi ve E vitamini içeriği sayesinde önemli antioksidan etkilere sahiptir. HDL'nin antioksidan kapasitesinin primer belirleyicisi olarak düşünülen PON1, spesifik olarak LDL ve HDL'deki okside lipidleri hidroliz ederek aterosklerotik lezyon gelişim risklerini azaltır [5,6]. PON1, karaciğerde sentezlenen, insan serumunda HDL yapısında bulunan, 43 kDa molekül ağırlığında, 355 amino asitten oluşan, glikoprotein yapısında Ca+2 bağımlı bir ester hidrolazdır [7,8].…”