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Atherosclerosis Dec 2015A soluble form of endoglin (sEng) is known to be an extracellular domain of the full-length membrane endoglin, which is elevated during various pathological conditions... (Review)
Review
A soluble form of endoglin (sEng) is known to be an extracellular domain of the full-length membrane endoglin, which is elevated during various pathological conditions related to vascular endothelium. In the current review, we tried to summarize a possible role of soluble endoglin in cardiovascular pathologies, focusing on its relation to endothelial dysfunction and cholesterol levels. We discussed sEng as a proposed biomarker of cardiovascular disease progression, cardiovascular disease treatment and endothelial dysfunction. We also addressed a potential interaction of sEng with TGF-β/eNOS or BMP-9 signaling. We suggest soluble endoglin levels to be monitored, because they reflect the progression/treatment efficacy of cardiovascular diseases related to endothelial dysfunction and hypercholesterolemia. A possible role of soluble endoglin as an inducer of endothelial dysfunction however remains to be elucidated.
Topics: Animals; Antigens, CD; Biomarkers; Cardiovascular Diseases; Endoglin; Endothelium, Vascular; Growth Differentiation Factor 2; Growth Differentiation Factors; Humans; Hypercholesterolemia; Nitric Oxide Synthase Type III; Prognosis; Receptors, Cell Surface; Signal Transduction; Transforming Growth Factor beta
PubMed: 26520890
DOI: 10.1016/j.atherosclerosis.2015.10.003 -
Advances in Experimental Medicine and... 2016Hypercholesterolemia is a serious health problem that is associated not only with heart disease, but also tendon pathology. In high cholesterol environments (e.g.... (Review)
Review
Hypercholesterolemia is a serious health problem that is associated not only with heart disease, but also tendon pathology. In high cholesterol environments (e.g. familial hyperlipidemia), lipids accumulate within the tendon extracellular matrix and form deposits called xanthomas. Lipid-related changes are known to affect several tendon mechanical properties, including stiffness and modulus, in uninjured and injured tendons, alike. Mechanisms to explain these cholesterol-related changes are multiple, including alterations in tenocyte gene and protein expression, matrix turnover, tissue vascularity, and cytokine production. Clinically, rotator cuff tear and Achilles tendon rupture are clearly associated with metabolic derangements, and elevated total cholesterol is often among the specific metabolic parameters implicated. Treatment of hypercholesterolemia using statin medications has also been shown to affect tendon properties, resulting in normalization of tendon thickness and improved tendon healing. Despite current work, the pathophysiology of lipid-related tendon pathology remains incompletely understood, and additional hypothesis-generating studies, including those incorporating whole-genome and whole-transcriptome technologies, will help to point the field in new directions.
Topics: Animals; Homeostasis; Humans; Hypercholesterolemia; Tendons
PubMed: 27535257
DOI: 10.1007/978-3-319-33943-6_14 -
Expert Opinion on Biological Therapy Feb 2017Low-density lipoprotein cholesterol (LDL-C) remains a well-established risk factor for cardiovascular disease (CVD). LDL-C levels are considered primary targets of... (Review)
Review
Low-density lipoprotein cholesterol (LDL-C) remains a well-established risk factor for cardiovascular disease (CVD). LDL-C levels are considered primary targets of therapy. A new series of systemic biomolecules, the monoclonal antibodies (mAbs) of proprotein convertase subtilisin/kexin type 9 (PCSK9), have a higher activity in reducing LDL-C. Areas covered: The authors critically review the current evidence on the efficacy and safety of bococizumab, a humanized mAb against PCSK9, which was surprisingly discontinued in November 2016. The pharmacokinetic profile and the biological features of bococizumab vs others mAbs are also discussed. As of now, in adjunct to diet, alirocumab and evolocumab are the only approved PCSK9 mAbs for the treatment of adult patients with severe clinical atherosclerotic CVD already at maximally-tolerated statin therapy and require additional LDL-C lowering. Expert opinion: Although discontinued, data from a phase 2b trial show the effectiveness of bococizumab in lowering LDL-C in a similar way to the two available PCSK9 antagonists. However, some peculiar biological characteristics of bococizumab may explain the attenuation of LDL-C lowering over time, as well as a higher rate of immunogenicity and of injection-site reactions.
Topics: Animals; Antibodies, Monoclonal, Humanized; Atherosclerosis; Cardiovascular Diseases; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; PCSK9 Inhibitors; Risk Factors; Treatment Outcome
PubMed: 28060539
DOI: 10.1080/14712598.2017.1279602 -
Praxis Aug 2017
Review
Topics: Adult; Aged; Algorithms; Cardiovascular Diseases; Dyslipidemias; Female; Guideline Adherence; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; PCSK9 Inhibitors; Risk
PubMed: 28830328
DOI: 10.1024/1661-8157/a002757 -
Pharmacological Research Jul 2023Despite a general improvement in global health conditions in the last decades, cardiovascular diseases (CVDs) are still the first global cause of death and disability... (Review)
Review
Despite a general improvement in global health conditions in the last decades, cardiovascular diseases (CVDs) are still the first global cause of death and disability worldwide, with ischemic heart disease (IHD) being responsible for half of CVD deaths. Hypercholesterolemia is a major causal risk factor for IHD. Although the availability of effective cholesterol-lowering drugs largely increased in the last few years, we are still facing disparities in the awareness of dyslipidaemia as a CVD-associated risk factor and therefore in health expenditure among different world areas. Although no significant changes have been reported globally in the levels of plasma cholesterol in the last three decades, relevant differences among world areas according to their economic status can be observed. Only high-income countries have experienced an improvement in plasma lipid profile which translated into a substantial decrease in the deaths and disabilities due to IHD, whereas countries in other income groups showed no reduction or even an increase. As expected, most of the deaths for IHD attributable to high LDL-C occur in people aged 60 years and above, although significant differences can be observed according to income. Altogether these observations suggest the need for measures to reduce the gap in treating hypercholesterolemia among income groups, with special attention to women and older people.
Topics: Humans; Female; Aged; Hypercholesterolemia; Myocardial Ischemia; Aging; Cardiovascular Diseases; Risk Factors; Cholesterol
PubMed: 37271426
DOI: 10.1016/j.phrs.2023.106814 -
Nutrients Feb 2021Hypercholesterolemia is a well-known independent risk factor for cardiovascular disease and a recognized target of pharmacological therapeutic agents in both primary and...
Hypercholesterolemia is a well-known independent risk factor for cardiovascular disease and a recognized target of pharmacological therapeutic agents in both primary and secondary prevention [...].
Topics: Cardiovascular Diseases; Diet, Healthy; Dietary Supplements; Food Ingredients; Heart Disease Risk Factors; Humans; Hypercholesterolemia
PubMed: 33652643
DOI: 10.3390/nu13030741 -
Praxis Aug 2022Arterial hypertension and hypercholesterolemia increase the risk of cardiovascular morbidity and mortality. Effectively reducing both blood pressure and circulating...
Arterial hypertension and hypercholesterolemia increase the risk of cardiovascular morbidity and mortality. Effectively reducing both blood pressure and circulating low-density lipoprotein cholesterol may considerably reduce cardiovascular risk. As this is particularly true if the intervention starts early, it is very important to identify and treat hypertension and hypercholesterolemia as early as possible. By improving adherence, a single-pill formulation that offers a combination of different drugs could be an effective way to manage patients with multiple cardiovascular risks.
Topics: Blood Pressure; Cardiovascular Diseases; Cholesterol, LDL; Humans; Hypercholesterolemia; Hypertension; Risk Factors
PubMed: 35920009
DOI: 10.1024/1661-8157/a003894 -
Current Atherosclerosis Reports Jun 2022Common DNA variants with small effects work together to create susceptibility to polygenic hypercholesterolemia. Some clinicians wonder whether patients with polygenic... (Review)
Review
PURPOSE OF REVIEW
Common DNA variants with small effects work together to create susceptibility to polygenic hypercholesterolemia. Some clinicians wonder whether patients with polygenic hypercholesterolemia have less severe clinical features compared to patients with monogenic familial hypercholesterolemia (FH) caused by rare deleterious variants.
RECENT FINDINGS
Studies performed in cohorts of patients with both monogenic and polygenic hypercholesterolemia have assessed lipid levels, non-invasive markers of atherosclerosis, and clinical end points, including major adverse cardiovascular events. The totality of data suggests a gradient across genotypes. Specifically, individuals with polygenic hypercholesterolemia have deleterious phenotypes that are intermediate in severity between those in patients with monogenic hypercholesterolemia and in control subjects. Although clinical variables in patients with polygenic hypercholesterolemia are less severe than in those with monogenic hypercholesterolemia, cardiovascular risk is still very high in these patients compared to controls. Patients with polygenic hypercholesterolemia must be treated assertively.
Topics: Cardiovascular Diseases; Heart Disease Risk Factors; Humans; Hypercholesterolemia; Multifactorial Inheritance; Risk Factors
PubMed: 35386091
DOI: 10.1007/s11883-022-01018-6 -
European Journal of Internal Medicine Sep 2014Hypercholesterolemia is a well-established modifiable cardiovascular risk factor and its treatment is an essential aim in preventing cardiovascular disease. Current... (Review)
Review
Hypercholesterolemia is a well-established modifiable cardiovascular risk factor and its treatment is an essential aim in preventing cardiovascular disease. Current guidelines highlight lifestyle intervention as a primary issue in the treatment of the patient with hypercholesterolemia. Therapeutic lifestyle changes are often insufficient to achieve desirable cholesterol levels. This is particularly true for high risk patients; however, also low risk patients, whose cholesterol levels are not necessarily far from recommended targets, have either sub-optimal or even significantly increased lipid levels. Nutraceuticals are borderline devices between nutrients and drugs providing a supplementation of particular nutrients with beneficial effects on health. Several nutraceuticals have been suggested to improve plasma lipid profile. The literature counted over 40 nutraceutical substances with a supposed beneficial effect on lipid metabolism; for some of them a number of clinical trials highlighted a cholesterol lowering effect and a possible positive influence on cardiovascular prognosis. The aim of this article is to review the main evidences supporting or denying the efficacy and safety of some of the most commonly used nutraceuticals with supposed cholesterol lowering activity.
Topics: Anticholesteremic Agents; Cholesterol; Dietary Supplements; Humans; Hypercholesterolemia
PubMed: 24997485
DOI: 10.1016/j.ejim.2014.06.008 -
Drug and Therapeutics Bulletin Feb 2016▼Evolocumab (Repatha-Amgen Ltd) and ▼alirocumab (Praluent-Sanofi) are the first in a novel class of lipid-regulating drugs, proprotein convertase subtilisin/kexin... (Meta-Analysis)
Meta-Analysis Review
▼Evolocumab (Repatha-Amgen Ltd) and ▼alirocumab (Praluent-Sanofi) are the first in a novel class of lipid-regulating drugs, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, to be licensed in the UK. Both drugs have marketing authorisation for the treatment of primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia and are administered by subcutaneous injection. Here we consider the evidence for evolocumab and alirocumab in the management of primary hypercholesterolaemia and dyslipidaemias.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Dyslipidemias; Humans; Hypercholesterolemia; Lipid Regulating Agents
PubMed: 26868931
DOI: 10.1136/dtb.2016.2.0381