scholarly journals Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

2021 ◽  
Vol 22 (13) ◽  
pp. 6949
Author(s):  
Siarhei A. Dabravolski ◽  
Evgeny E. Bezsonov ◽  
Mirza S. Baig ◽  
Tatyana V. Popkova ◽  
Alexander N. Orekhov
Keyword(s):  
Heart Diseases ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Liver Mitochondria ◽  
Atherogenic Dyslipidemia ◽  
Cvd Risk ◽  
Alcoholic Fatty Liver ◽  
Cholesterol Levels ◽  
Mitochondrial Lipid ◽  
Cardioprotective Effects

The prevalence of NAFLD (non-alcoholic fatty liver disease) is a rapidly increasing problem, affecting a huge population around the globe. However, CVDs (cardiovascular diseases) are the most common cause of mortality in NAFLD patients. Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense LDL (low-density lipoprotein) particles, and decreased HDL-C (high-density lipoprotein cholesterol) levels, is often observed in NAFLD patients. In this review, we summarize recent genetic evidence, proving the diverse nature of metabolic pathways involved in NAFLD pathogenesis. Analysis of available genetic data suggests that the altered operation of fatty-acid β-oxidation in liver mitochondria is the key process, connecting NAFLD-mediated dyslipidemia and elevated CVD risk. In addition, we discuss several NAFLD-associated genes with documented anti-atherosclerotic or cardioprotective effects, and current pharmaceutical strategies focused on both NAFLD treatment and reduction of CVD risk.

Abstract P326: Perceived Neighborhood Crime is Associated With Serum Cholesterol Levels Among Females, but Not Males: Santiago Longitudinal Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Erin M Delker ◽  
Estela Blanco ◽  
Patricia East ◽  
Raquel Burrows ◽  
Jorge Delva ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Serum Cholesterol ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Neighborhood Crime ◽  
Cvd Risk ◽  
Middle Income ◽  
Cholesterol Levels ◽  
Sex Crime

Introduction: In a Chilean sample, adolescents’ CVD risk factors were associated with perceived neighborhood crime. To determine if this effect was sustained, we examined associations between adolescents’ perceived neighborhood crime and their serum cholesterol levels in young adulthood. Neighborhood stress has been cross-sectionally related to dyslipidemia in previous studies. Hypothesis: (1) Higher levels of perceived crime will be associated with higher low-density lipoprotein (LDL) cholesterol and lower high-density lipoprotein (HDL). (2) Sex will modify this association. Methods: Data were from adolescent (x =14 yrs) and young adult waves (x =22 yrs) of the Santiago Longitudinal Study (N=645). Perceived neighborhood crime was measured using three scale items about neighborhood drug use, muggings, burglaries and assaults. Crime was analyzed as a continuous and categorical variable. Fasting HDL and LDL cholesterol (mg/dL) were measured at 22 yrs. Associations between crime and HDL and LDL were analyzed by linear regression, adjusting for sex, age and SES. Effect modification by sex was tested with sex*crime interaction. Results: Participants were low-middle income and 55% female. Females perceived slightly more crime than males (F: x =9.1 M: x =8.8, p=0.30). There was a significant sex*crime interaction for HDL (p=0.03) and LDL (p=0.01). Among males, average HDL and LDL were 100±32 and 41±12; crime did not relate to either outcome. Among females, average HDL and LDL were 100±28 and 46±14; neighborhood crime was negatively associated with HDL and positively associated with LDL. For example, females reporting the most crime had, on average, 7.5 mm/dL lower HDL and 12.8 mm/dL higher LDL than females reporting the least amount of crime (Fig. 1). Conclusions: Perceived crime was prospectively associated with worse lipid profiles among females but not males. A sex-specific stress mechanism may be operating. Further study of the physiologic and behavioral mechanisms contributing to these findings is needed.

scholarly journals Working towards full eradication of lipid-driven cardiovascular risk?

2021 ◽  
Author(s):  
N. S. Nurmohamed ◽  
E. S. G. Stroes
Keyword(s):  
Clinical Investigation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Current Standard ◽  
Cvd Risk ◽  
Cholesterol Levels ◽  
Post Hoc ◽  
High Triglyceride

AbstractLipid-driven cardiovascular disease (CVD) risk is caused by atherogenic apolipoprotein B (apoB) particles containing low-density lipoprotein cholesterol (LDL-C), triglycerides and lipoprotein(a) [Lp(a)] and resembles a large and modifiable proportion of the total CVD risk. While a surplus of novel lipid-lowering therapies has been developed in recent years, management of lipid-driven CVD risk in the Netherlands remains suboptimal. To lower LDL‑C levels, statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibiting antibodies are the current standard of therapy. With the approval of bempedoic acid and the silencing RNA inclisiran, therapeutic options are expanding continuously. Although the use of triglyceride-lowering therapies remains a matter of debate, post hoc analyses consistently show a benefit in subsets of patients with high triglyceride or low high-density lipoprotein cholesterol levels. Pemafibrate and novel apoC-III could be efficacious options when approved for clinical use. Lp(a)-lowering therapies such as pelacarsen are under clinical investigation, offering a potent Lp(a)-lowering effect. If proven effective in reducing cardiovascular endpoints, Lp(a) lowering holds promise to be the third axis of effective lipid-lowering therapies. Using these three components of lipid-lowering treatment, the contribution of apoB-containing lipid particles to the CVD risk may be fully eradicated in the next decade.

scholarly journals Hypolipidemic therapy in patients with non-alcoholic fatty liver disease

2010 ◽  
Vol 1 (1) ◽  
pp. 38-45
Author(s):  
L. B Lazebnik ◽  
L. A Zvenigorodskaya ◽  
N. G Samsonova ◽  
E. A Cherkasova ◽  
N. V Melnikova
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Atherogenic Dyslipidemia ◽  
Cardiovascular Risks ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Dyslipidemia is currently accepted to be one of the major risk factor for cardiovascular diseases and atherosclerosis. There is no question that the liver plays an important role in the development of atherogenic dyslipidemia and it is simultaneously a target organ, which results in the development of non-alcoholic fatty liver disease (NAFLD). The latter limits the feasibilities of adequate hypolipidemic therapy, thus increasing the cardiovascular risks. There is a need to use hepatoprotectors when atherogenic dyslipidemia in a patient with documented NAFLD is treated with statins and fibrates. The choice of hepatoprotectors depends on the stage of NAFLD. It is expedient to take statins in combination with ursodeoxycholic acid preparations in NAFLD at the stage of steatosis. A combination of statins and a cholesterol absorption inhibitor is more effective in achieving low-density lipoprotein cholesterol goals in patients with hypercholesterolemia. Intestinal microflora-normalizing agents (enteric antiseptics, pre- and probiotics) should be included into a complex of hypolipidemic therapy in patients with NAFLD. Key words: atherogenic dyslipidemia, non-alcoholic fatty liver disease, hypolipidemic therapy.

scholarly journals Understanding the Impact of Dietary Cholesterol on Chronic Metabolic Diseases through Studies in Rodent Models

Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 939 ◽  
Author(s):  
Ángela Vinué ◽  
Andrea Herrero-Cervera ◽  
Herminia González-Navarro
Keyword(s):  
Metabolic Diseases ◽  
Low Density Lipoprotein ◽  
Dietary Cholesterol ◽  
Density Lipoprotein ◽  
Metabolic Complications ◽  
Alcoholic Fatty Liver ◽  
Cholesterol Levels ◽  
Human Pathology ◽  
Key Factor ◽  
The Impact

The development of certain chronic metabolic diseases has been attributed to elevated levels of dietary cholesterol. However, decades of research in animal models and humans have demonstrated a high complexity with respect to the impact of dietary cholesterol on the progression of these diseases. Thus, recent investigations in non-alcoholic fatty liver disease (NAFLD) point to dietary cholesterol as a key factor for the activation of inflammatory pathways underlying the transition from NAFLD to non-alcoholic steatohepatitis (NASH) and to hepatic carcinoma. Dietary cholesterol was initially thought to be the key factor for cardiovascular disease development, but its impact on the disease depends partly on the capacity to modulate plasmatic circulating low-density lipoprotein (LDL) cholesterol levels. These studies evidence a complex relationship between these chronic metabolic diseases and dietary cholesterol, which, in certain conditions, might promote metabolic complications. In this review, we summarize rodent studies that evaluate the impact of dietary cholesterol on these two prevalent chronic diseases and their relevance to human pathology.

PCSK9 Inhibitors: Novel Therapeutic Strategies for Lowering LDLCholesterol

2018 ◽  
Vol 19 (2) ◽  
pp. 165-176 ◽  
Author(s):  
Yan Wang ◽  
Zhao-Peng Liu
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Maximum Tolerated Dose ◽  
Therapeutic Strategies ◽  
Low Density ◽  
Pcsk9 Inhibitors ◽  
Cvd Risk ◽  
Safety Issues ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Statins are currently the major therapeutic strategies to lower low-density lipoprotein cholesterol (LDL-C) levels. However, a number of hypercholesterolemia patients still have a residual cardiovascular disease (CVD) risk despite taking the maximum-tolerated dose of statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein receptor (LDLR), inducing its degradation in the lysosome and inhibiting LDLR recirculating to the cell membranes. The gain-offunction mutations in PCSK9 elevate the LDL-C levels in plasma. Therefore, PCSK9 inhibitors become novel therapeutic approaches in the treatment of hypercholesterolemia. Several PCSK9 inhibitors have been under investigation, and much progress has been made in clinical trials, especially for monoclonal antibodies (MoAbs). Two MoAbs, evolocumab and alirocumab, are now in clinical use. In this review, we summarize the development of PCSK9 inhibitors, including antisense oligonucleotides (ASOs), small interfering RNA (siRNA), small molecule inhibitor, MoAbs, mimetic peptides and adnectins, and the related safety issues.

scholarly journals Genetic variation of RNF145 gene and blood lipid levels in Xinjiang population, China

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jing Ming ◽  
Xian Wei ◽  
Min Han ◽  
Dilare Adi ◽  
Jialin Abuzhalihan ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Ring Finger ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Lipid Profiles ◽  
Cholesterol Levels ◽  
General Linear Model Analysis ◽  
Confounding Variables ◽  
Before And After ◽  
Detection Response

AbstractDyslipidemia is one of the main risk factors for coronary heart disease (CHD). The E3 ubiquitin ligase which is encoded by the ring finger protein 145 (RNF145) gene is very important in the mediation of cholesterol synthesis and effectively treats hypercholesterolemia. Thus, the purpose of the present research is to investigate the connection between the polymorphism of the RNF145 gene and cholesterol levels in the populations in Xinjiang, China. A total of 1396 participants (Male: 628, Female: 768) were included in this study for genetic analysis of RNF145 gene, and we used the modified multiple connection detection response (iMLDR) technology to label two SNPs (rs17056583, rs12188266) of RNF145 genotyping. The relationship between the genotypes and the lipid profiles was analyzed with general linear model analysis after adjusting confounding variables. Through the analysis of the two SNPs in RNF145 gene, we discovered that both rs17056583 and rs12188266 were related to total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations (All P < 0.001). In addition, the association of rs17056583 and rs12188266 with lipid profiles concentrations is still statistically significant after multivariate adjustment of sex, age, smoking, obesity, drinking, diabetes, hypertension and lipid profiles. Meanwhile, we also found that rs17056583 was associated with high triglycerides concentrations before and after adjustment (All P < 0.001). Our study shows that both rs17056583 and rs12188266 SNPs of RNP145 gene are related to TC and LDL-C concentrations in Xinjiang population.

scholarly journals Sulforaphane ameliorates lipid profile in rodents: an updated systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaili Du ◽  
Yuxin Fan ◽  
Dan Li
Keyword(s):  
Systematic Review ◽  
Weight Control ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Disease Model ◽  
Density Lipoprotein ◽  
Liver Weight ◽  
Lipoprotein Cholesterol ◽  
Alcoholic Fatty Liver

AbstractSulforaphane (SFN), a naturally-occurring isothiocyanate enriched in cabbage and broccoli, has been provided as food supplements to improve weight management and reduce lipid levels. However, its effects on serum lipid profiles are contradictory. In this review, a meta-analysis and systematic review of SFN on lipid reduction and weight control is assessed with mice and rats fed on high-fat diet. The effects of SFN supplementation were evaluated by weighted mean difference (WMD) in body weight (BW), liver weight (LW) and also by its effect on serum lipids. A random-effects model was applied to estimate the overall summary effect. SFN reduced BW (WMD: − 2.76 g, 95% CI: − 4.19, − 1.34) and LW (WMD: − 0.93 g, 95% CI: − 1.63, − 0.23) significantly in our ten trials. Its effects on serum total cholesterol (TC) (WMD: − 15.62 mg/dL, 95% CI: − 24.07, − 7.18), low-density lipoprotein cholesterol (LDL-C) (WMD: − 8.35 mg/dL, 95% CI: − 15.47, − 1.24) and triglyceride (TG) (WMD: − 40.85 mg/dL, 95% CI: − 67.46, − 14.24) were significant except for high-density lipoprotein cholesterol (HDL-C) component (WMD: 1.05 mg/dL, 95% CI: − 3.44, 5.54). However, species, disease model, duration, SFN dosage as well as route of administration did not explain the heterogeneity among studies. In summary, these findings provide new insights concerning preclinical strategies for treating diseases including obesity, diabetes, hypertension, non-alcoholic fatty liver disease as well as cardiovascular disease with SFN supplements.

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