Therapeutic Management of Familial Hypercholesterolemia: Current and Emerging Drug Therapies

Patel, Roshni S.; Scopelliti, Emily M.; Savelloni, Julie

doi:10.1002/phar.1672

Cited by 18 publications

(8 citation statements)

References 58 publications

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“…LDL promotes the formation of fatty streaks and induces the uptake of oxidized LDL by smooth muscle and macrophages cells. By contrast, HDL can inhibit LDL oxidation via various mechanisms [25]. We found that LDL and HDL levels in the HFD group were respectively enhanced and reduced compared with those in the normal diet group.…”

Section: Resultsmentioning

confidence: 63%

Preventive Effects of Total Flavonoid C-Glycosides from Abrus mollis on Nonalcoholic Fatty Liver Disease through Activating the PPARα Signaling Pathway

Niu

Chen

et al. 2019

Planta Med

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Abrus pulchellus subsp. mollis (Hance) Verdc. (Leguminosae) is a well-known edible plant usually added to soups and beverages. In this study, vicenin-2 (1), isoschaftoside (2), schaftoside (3), and their enrichment fraction, total flavonoid C-glycosides, derived from the extracts of A. mollis, were firstly found to prevent nonalcoholic fatty liver disease both in vitro and in vivo. In the in vitro study, total flavonoid C-glycosides decreased the lipid accumulation in oleic acid-treated HepG2 cells. The mechanisms of total flavonoid C-glycosides are involved in the regulation of peroxisome proliferator-activated receptor α and its downstream, and the reduction of proinflammatory cytokines. In high-fat diet-induced fatty liver rats, total flavonoid C-glycosides decreased the levels of glutamic-oxalacetic transaminease and glutamic-pyruvic transaminase, and decreased the lipid accumulation both in the liver and blood without affecting food intake. In addition, total flavonoid C-glycosides also increased the activities of the antioxidant enzyme system in vivo. In conclusion, total flavonoid C-glycosides are active components of A. mollis on nonalcoholic fatty liver disease, and can be used in functional food and supplements for nonalcoholic fatty liver disease prevention and treatment.

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Section: Resultsmentioning

confidence: 63%

Preventive Effects of Total Flavonoid C-Glycosides from Abrus mollis on Nonalcoholic Fatty Liver Disease through Activating the PPARα Signaling Pathway

Niu

Chen

et al. 2019

Planta Med

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“…The primary screening target for FH is the LDLR pathogenic variants, accounting for more than 90% of the FH cases (Hartgers et al, 2015 ). In the remaining cases, the second in prevalence gene mutation involves ApoB (2–5% of cases) (Patel et al, 2015 ), an apolipoprotein that is found on each LDL particle and is responsible for the specific ligand-receptor binding and the subsequent clearance of LDL from the circulation (Walldius and Jungner, 2004 ). In these cases, the mutant apolipoprotein B-100 (specific for LDL, IDL, and VLDL) impairs the binding of the ApoB-containing particles by the LDLR in the liver, resulting in their accumulation in the systemic circulation which further triggers atherogenesis (Walldius and Jungner, 2004 ; Patel et al, 2015 ).…”

Section: Fh Geneticsmentioning

confidence: 99%

Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management

et al. 2018

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Familial hypercholesterolemia (FH) is a common genetic cause of premature cardiovascular disease (CVD). The reported prevalence rates for both heterozygous FH (HeFH) and homozygous FH (HoFH) vary significantly, and this can be attributed, at least in part, to the variable diagnostic criteria used across different populations. Due to lack of consistent data, new global registries and unified guidelines are being formed, which are expected to advance current knowledge and improve the care of FH patients. This review presents a comprehensive overview of the pathophysiology, epidemiology, manifestations, and pharmacological treatment of FH, whilst summarizing the up-to-date relevant recommendations and guidelines. Ongoing research in FH seems promising and novel therapies are expected to be introduced in clinical practice in order to compliment or even substitute current treatment options, aiming for better lipid-lowering effects, fewer side effects, and improved clinical outcomes.

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“…A negative correlation has been demonstrated between LDL and high-density lipoproteins (HDLs). High level of HDL can inhibit LDL oxidation by various mechanisms [1]. Several studies have shown that natural ingredients are effective in preventing hypercholesterolemia by suppressing LDL oxidation [2].…”

Section: Introductionmentioning

confidence: 99%

Citrus junos Tanaka peel ameliorates hepatic lipid accumulation in HepG2 cells and in mice fed a high-cholesterol diet

Shin

Park

Sung

et al. 2016

BMC Complement Altern Med

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Background Citrus junos Tanaka (yuja), a yellow-coloured citrus fruit has traditionally been consumed in Korea, Japan, and China and has been found effective in preventing certain diseases. However, the inhibitory effect of yuja on hepatic lipid accumulation has not been clearly elucidated thus far.MethodsThe inhibitory effect of yuja on hepatic lipid accumulation was investigated in both cell culture and mouse models. We investigated the inhibitory effect of ethanol extract of yuja peel (YE) using HepG2 cells. We next confirmed the effect of YE in mice fed a high cholesterol diet. Animals were divided into 4 groups (n = 8): a normal diet group (ND), a high-cholesterol diet group (HC), high-cholesterol diet plus 1% YE (YL), high-cholesterol diet plus 5% YE (YH).ResultSeventy percent ethanolic extracts of yuja peel (YE) reduced oleic acid-induced hepatic lipid accumulation in HepG2 cells. Treatment with YE at 100, 200 μg/mL up-regulated expression levels of cholesterol metabolism-related proteins such as AMPK, ACC, PPAR-α, and CPT1 and down-regulated the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase. The hypocholesterolemic effect of YE was further confirmed in mice fed a high-cholesterol diet. Compared to ND (normal diet) mice, HC (high-cholesterol diet) mice showed increased body weight, liver fat content, liver weight, and content of total cholesterol and low-density lipoprotein (LDL) cholesterol. On the contrary, administrations of YL (HC + 1% YE) or YH (HC + 5% YE) significantly reduced body weight, liver fat content, liver weight, total cholesterol, and LDL cholesterol compared to those of only HC fed mice group. As a result of in vitro data, protein expressions of PPAR-α and CPT1 were induced in mice fed YE diet compared to HC diet but HMGCR expression was decreased.ConclusionsYuja peel ameliorates hepatic lipid accumulation in both cell culture and mouse models and therefore, could serve as a useful supplement for hypercholesterolemia.

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Therapeutic Management of Familial Hypercholesterolemia: Current and Emerging Drug Therapies

Cited by 18 publications

References 58 publications

Preventive Effects of Total Flavonoid C-Glycosides from Abrus mollis on Nonalcoholic Fatty Liver Disease through Activating the PPARα Signaling Pathway

Preventive Effects of Total Flavonoid C-Glycosides from Abrus mollis on Nonalcoholic Fatty Liver Disease through Activating the PPARα Signaling Pathway

Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management

Citrus junos Tanaka peel ameliorates hepatic lipid accumulation in HepG2 cells and in mice fed a high-cholesterol diet

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