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Hormones (Athens, Greece) Dec 2023Hypercholesterolemia due to a high-cholesterol diet is linked to numerous diseases and may lead to male infertility. However, the underlying mechanism remains unknown....
PURPOSE
Hypercholesterolemia due to a high-cholesterol diet is linked to numerous diseases and may lead to male infertility. However, the underlying mechanism remains unknown. The maintenance of male fertility requires intact testicular structures (including seminiferous tubules and mesenchyme) and functioning cells (Leydig cells, Sertoli cells and germ cells, etc.), production of appropriate concentrations of sex hormones, and cooperation among testicular cells. Thus, we considered whether male fertility declined as the structure and function of testicular cells were altered in rats on a high-cholesterol diet.
METHODS
Male Sprague Dawley rats were fed either a standard or a high-cholesterol diet for 16 weeks. Serum sex hormones, lipid components, semen quality, and fertility rate were assayed in the rats. The 3β-hydroxysteroid dehydrogenase (3β-HSD), Wilms tumor 1 (WT-1), and deleted in azoospermia-like (DAZL) were regarded as specific markers of Leydig, Sertoli, and germ cells in rats. In addition, the ultrastructure of the testis and expression levels of particular marker molecules of testicular cells were further investigated.
RESULTS
Compared to rats fed on a regular diet, the serum testosterone levels and sperm progressive motility decreased in rats fed high cholesterol. Moreover, we observed a deformed nucleus, dilated smooth endoplasmic reticulum, and swollen mitochondria of Leydig cells and a schizolytic nucleus of Sertoli cells in rats on a high-cholesterol diet. The 3β-HSD, WT-1, and DAZL protein expression levels were significantly reduced in rats on a high-cholesterol diet.
CONCLUSIONS
Our results showed that a high-cholesterol diet adversely affected testosterone production and sperm progressive motility, possibly due to Leydig, Sertoli, and germ cell abnormalities.
Topics: Humans; Male; Rats; Animals; Hypercholesterolemia; Semen Analysis; Rats, Sprague-Dawley; Semen; Testis; Leydig Cells; Testosterone; Testicular Diseases; Diet; Cholesterol
PubMed: 37596375
DOI: 10.1007/s42000-023-00472-4 -
Journal of Clinical Lipidology 2023Mortality and morbidity in people with Type 1 diabetes (T1D) is mainly caused by cardiovascular disease (CVD). Early treatment of cardiovascular risk factors (CVRFs) is...
BACKGROUND
Mortality and morbidity in people with Type 1 diabetes (T1D) is mainly caused by cardiovascular disease (CVD). Early treatment of cardiovascular risk factors (CVRFs) is of great importance.
OBJECTIVE
To analyze the prevalence of LDL-hypercholesterolemia and other CVRFs in youth with T1D.
METHODS
Clinical and laboratory parameters, and vascular thickness measurement were obtained in youth with T1D (age 6-18 years, T1D duration >1 year) attending a diabetes clinic. LDL-hypercholesterolemia, microalbuminuria and arterial hypertension were defined as CVRFs.
RESULTS
A total of 333 youth (48% girls; age: 13.3 years [10.3-15.5], median [interquartile range]) participated in the study. The T1D duration was 5.9 years [3.5-9.4] with HbA1c of 7.4% [6.8-8.0]. Intima media thickness (N=223) was 538.0 µm [470.0-618.0]). LDL-hypercholesterolemia was present in 30 participants (9%; 18 girls; age: 14.3 years [11.2-15.7]). None of the participants had persistent microalbuminuria, although 59 (18.3%) had elevated albumin excretion in a random urine specimen. LDL-hypercholesterolemia was associated with increased blood pressure (p<0.05), insulin requirement (p<0.05), HbA1c (p<0.05), triglyceride (p<0.001) and total cholesterol (p<0.001), and a family history of premature CVD (p<0.001), but negatively correlated with HDL cholesterol levels (p<0.05). Sex, pubertal status, duration of diabetes, type of therapy, and physical activity did not differ between participants with and without LDL- hypercholesterolemia. Arterial hypertension was present in 11 participants (3.3%; 4 girls; age: 14.1 years [11.1-16.1]).
CONCLUSION
LDL-hypercholesterolemia affected 9% of youth with T1D in this cohort and was associated with other CVRFs. A holistic therapeutic concept for these young people is essential.
Topics: Female; Adolescent; Humans; Child; Male; Diabetes Mellitus, Type 1; Cardiovascular Diseases; Hypercholesterolemia; Risk Factors; Glycated Hemoglobin; Prevalence; Carotid Intima-Media Thickness; Hypertension; Heart Disease Risk Factors
PubMed: 37258406
DOI: 10.1016/j.jacl.2023.05.097 -
Expert Opinion on Biological Therapy Sep 2017LDL-cholesterol (LDL-C) is one of the most well-established risk factors for CV disease. Indeed, therapies that decrease LDL-C are proven to effectively reduce the risk... (Review)
Review
LDL-cholesterol (LDL-C) is one of the most well-established risk factors for CV disease. Indeed, therapies that decrease LDL-C are proven to effectively reduce the risk of atherosclerotic CV disease. Monoclonal antibodies (mAbs) that target proprotein convertase subtilisin/kexin type 9 (PCSK9) have recently gained traction as a promising therapeutic strategy. Areas covered: In this review, the authors discuss the effectiveness of mAbs against PCSK9 in lowering low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipid fractions. The discontinuation in the development of bococizumab due to efficacy and safety concerns, and the initial promising data about inclisiran, a long-acting small inhibiting RNA molecule against PCSK9 synthesis, is also discussed. Expert opinion: Initial data about cardiovascular (CV) outcomes in large scale, long-term studies suggest a possible further therapeutic pathway for LDL-C reduction, and currently support the notion that further LDL-C reduction, obtained with PCSK9 inhibition on top of best available therapy, provides increased CV protection in subjects at very high CV risk. The development and marketing of mAbs against PCSK9 could help to redefine current therapeutic strategies aimed at reducing cardiovascular (CV) morbidity and risk, through the reduction of LDL-C concentrations. The cost-effectiveness of these emerging drugs is yet to be established.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Cholesterol, LDL; Humans; Hypercholesterolemia; PCSK9 Inhibitors; Proprotein Convertase 9; RNA, Small Interfering; Risk Factors
PubMed: 28617192
DOI: 10.1080/14712598.2017.1341485 -
Medicina Clinica Feb 2016An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians' inappropriate or insufficient use of... (Review)
Review
An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians' inappropriate or insufficient use of cholesterol lowering medications or to patients' bad tolerance or therapeutic compliance. Another cause is an insufficient efficacy of current cholesterol lowering drugs including statins and ezetimibe. In addition, proprotein convertase subtilisin kexin type 9 inhibitors are a new cholesterol lowering medications showing safety and high efficacy to reduce c-LDL in numerous already performed or underway clinical trials, potentially allowing an optimal control of hypercholesterolemia in most patients. Agents inhibiting apolipoprotein B synthesis and microsomal transfer protein are also providing a new potential to decrease cholesterol in patients with severe hypercholesterolemia and in particular in homozygote familial hypercholesterolemia. Last, cholesteryl ester transfer protein inhibitors have shown powerful effects on c-HDL and c-LDL, although their efficacy in cardiovascular prevention and safety has not been demonstrated yet. We provide in this article an overview of the main characteristics of therapeutic agents for hypercholesterolemia, which have been recently approved or in an advanced research stage.
Topics: Anticholesteremic Agents; Biomarkers; Cholesterol, LDL; Humans; Hypercholesterolemia; Treatment Outcome
PubMed: 25817449
DOI: 10.1016/j.medcli.2015.01.016 -
Vascular Health and Risk Management 2014Medication nonadherence is a prevalent public health issue that contributes to significant medical costs and detrimental health outcomes. This is especially true in... (Review)
Review
Medication nonadherence is a prevalent public health issue that contributes to significant medical costs and detrimental health outcomes. This is especially true in patients with hypercholesterolemia, a condition affecting millions of American adults and one that is associated with increased risk for coronary and cerebrovascular events. Considering the magnitude of outcomes related to this disease, the medical community has placed significant emphasis on addressing the treatment for high cholesterol, and progress has been made in recent years. However, poor adherence to therapy continues to plague health outcomes and more must be understood and done to address suboptimal medication taking. Here we provide an overview of the reasons for poor medication adherence in patients with hypercholesterolemia and describe recent efforts to curb nonadherence. Suggested approaches for improving medication taking in patients with high cholesterol are also provided to guide practitioners, patients, and payers.
Topics: Anticholesteremic Agents; Health Knowledge, Attitudes, Practice; Humans; Hypercholesterolemia; Medication Adherence; Patient Education as Topic; Patients; Risk Factors; Treatment Outcome
PubMed: 25395859
DOI: 10.2147/VHRM.S56056 -
Drugs May 2020Bempedoic acid is a non-statin antihyperlipidaemic drug being developed by Esperion Therapeutics for the treatment of hypercholesterolaemia. Based on positive findings... (Review)
Review
Bempedoic acid is a non-statin antihyperlipidaemic drug being developed by Esperion Therapeutics for the treatment of hypercholesterolaemia. Based on positive findings in the phase III CLEAR clinical trial programme, bempedoic acid has been approved in the USA and in the EU as monotherapy (NEXLETOL in the USA, Nilemdo in the EU) and as a fixed-dose combination with ezetimibe (NEXLIZET in the USA, Nustendi in the EU). This article summarizes the milestones in the development of bempedoic acid leading to these first approvals.
Topics: Dicarboxylic Acids; Drug Approval; Fatty Acids; Humans; Hypercholesterolemia; Hypolipidemic Agents; Molecular Structure
PubMed: 32314225
DOI: 10.1007/s40265-020-01308-w -
Deutsche Medizinische Wochenschrift... Mar 2019Atherosclerotic cardiovascular disease is the leading cause of premature mortality and morbidity worldwide. Dyslipidemia is a commonly encountered clinical condition and... (Review)
Review
Atherosclerotic cardiovascular disease is the leading cause of premature mortality and morbidity worldwide. Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. The causality of plasma low-density lipoprotein-cholesterol (LDL-C) in the pathophysiology of cardiovascular disease has been established beyond any reasonable doubt. In this context, individual risk estimation, the determination of target values and lipid-lowering strategies represent an essential part and a challenge in the daily clinical practice to prevent cardiovascular events. Statins are recommended as first-line therapy for patients with hypercholesterolemia in secondary prevention. Controversies remain in the context of primary prevention, however, as to which kind of subjects to treat, the magnitude of the benefit, and potential harm. This article gives a brief overview of the current evidence, guideline recommendations and strategies for lowering of LDL-C in the primary prevention of cardiovascular disease.
Topics: Humans; Hypercholesterolemia; Practice Guidelines as Topic; Primary Prevention
PubMed: 30836403
DOI: 10.1055/a-0657-1668 -
Semergen Oct 2020The COVID-19 pandemic has shown that cardiovascular diseases carry a higher risk of mortality. Doubts have been raised regarding lipid therapy in these patients. The... (Review)
Review
BACKGROUND AND OBJECTIVES
The COVID-19 pandemic has shown that cardiovascular diseases carry a higher risk of mortality. Doubts have been raised regarding lipid therapy in these patients. The objectives are to analyze the efficacy and safety of lipid lowering therapy in patients with COVID-19.
MATERIAL AND METHODS
A review of the scientific literature was conducted in PubMed, CDC Reports, NIH, and NCBI SARS-CoV-2 using the keywords: COVID-2, statins, ezetimibe, PCSK9 inhibitors, hypercholesterolemia, and hypolipidemic drugs.
RESULTS
The statins should continue to use patients with COVID-19 based on their efficacy, safety, immunosuppressive effects, anti-inflammatory availability and accessibility. Depending on the cardiovascular risk levels of these patients, the use of high potency statins and/or ezetimibe and/or iPCSK9 may be necessary in patients with high and very high cardiovascular risk. Patients treated with iPCSK9 should continue treatment for its beneficial effects in preventing cardiovascular disease. Patients with familial hypercholesterolemia and COVID-19 are especially vulnerable to cardiovascular disease and should continue to receive severe lipid lowering therapy.
CONCLUSIONS
In patients with COVID-19, the majority of baseline CVDs are of atherosclerotic origin, with the worst prediction for patients with high risk and very high risk of CVD. In these patients, intensive treatment with statins and/or fixed combination with ezetimibe and/or iPCSK9 plays a fundamental role.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Hypercholesterolemia; Hypolipidemic Agents; Pandemics; Patient Safety; Pneumonia, Viral; SARS-CoV-2
PubMed: 32718781
DOI: 10.1016/j.semerg.2020.06.014 -
British Journal of Pharmacology Jun 2017Growing attention is now being given to the possible preventive/alternative ways to avoid illness onset. Changes in lifestyle and food habits are taking over from the... (Review)
Review
UNLABELLED
Growing attention is now being given to the possible preventive/alternative ways to avoid illness onset. Changes in lifestyle and food habits are taking over from the conventional pharmaceutical-based approach, especially for chronic pathologies. Nutraceuticals have been proposed as key tools for the prevention and cure of some pathological conditions. This is leading research to develop new formulations based on these pharma-foods addressed in a specific way to prevent and cure health issues, which, in turn, will have an effect on therapy-related costs sustained by any National Health Organization. According to existing regulations, nutraceuticals cannot be categorized as either food or drugs but, by definition, often inhabit a grey area in between the two, being assimilated into food supplements, notwithstanding the beneficial properties that they can provide for some pathological conditions. A nutraceuticals-based approach for health management, in particular for some pathological conditions, has resulted in a worldwide growing 'nutraceutical' revolution. An outstanding example is the approach to the 'metabolic syndrome', which includes overweight, obesity and cardiovascular-related diseases, causing a sort of cascade of chronic health conditions, which is becoming a norm in modern life. Hypercholesterolaemia is one of these. It represents an example of a pathology that can be linked to both a poor lifestyle and dietary habits. The nutraceutical approach to hypercholesterolaemia is described in the present review as a possible alternative to the conventional drug-based therapy.
LINKED ARTICLES
This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.
Topics: Animals; Dietary Supplements; Feeding Behavior; Humans; Hypercholesterolemia; Life Style; Metabolic Syndrome
PubMed: 27685833
DOI: 10.1111/bph.13636 -
Current Atherosclerosis Reports Aug 2021In this review, we discuss strategies for managing dyslipidemia in pregnant women with ASCVD. (Review)
Review
PURPOSE OF REVIEW
In this review, we discuss strategies for managing dyslipidemia in pregnant women with ASCVD.
RECENT FINDINGS
Cardiovascular disease (CVD) is the leading cause of mortality in women as well as the leading cause of pregnancy-related mortality in the USA. It is paramount to screen, identify, counsel, and treat women of childbearing age who have existing atherosclerotic disease to mitigate the risks of complications and mortality. Dyslipidemias, including hypercholesterolemia and hyperlipidemia, can further enhance the risk for future CVD events. Treating hypercholesterolemia during pregnancy is crucial, and this is an opportune time for cross-collaboration of subspecialties in cardiology, obstetrics, and gynecology.
Topics: Atherosclerosis; Cardiovascular Diseases; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Pregnancy; Pregnant Women; Risk Factors
PubMed: 34345940
DOI: 10.1007/s11883-021-00957-w