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https://www.readbyqxmd.com/read/28930591/lipoprotein-a-and-cardiovascular-disease-current-state-and-future-directions-for-an-enigmatic-lipoprotein
#1
Anum Saeed, Salim S Virani
Lipoprotein (a) (Lp (a)) is a complex polymorphic lipoprotein. Although structurally similar to low-density lipoprotein, Lp(a) has a glycoprotein, apolipoprotein(a) (apo(a)), attached to the apolipoprotein B-100 component. Several unique properties of Lp(a) can be attributed to the presence of apo(a). Several decades of research has improved our understanding of the structure, biochemistry, and pathophysiology of Lp(a) associated diseases. Genetic, epidemiological, and translational data indicate that elevated Lp(a) levels are likely in the causal pathway for atherosclerotic cardiovascular diseases as well as calcification of the aortic valves...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28902717/new-approaches-to-address-dyslipidemia
#2
Klaus G Parhofer
PURPOSE OF REVIEW: Although lipid-lowering treatment with statins, ezetimibe, and PCSK9 inhibitors is a very successful strategy to prevent cardiovascular events, there is a need for further drug developments. Not all patients respond sufficiently to the available therapy (very high baseline values, intolerance). Furthermore, patients may be characterized by dyslipidemias not accessible to available drugs such as patients with homozygous familial hypercholesterolemia, chylomicronemia syndrome, or elevated lipoprotein(a)...
September 11, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28888913/the-renaissance-of-lipoprotein-a-brave-new-world-for-preventive-cardiology
#3
REVIEW
Katrina L Ellis, Michael B Boffa, Amirhossein Sahebkar, Marlys L Koschinsky, Gerald F Watts
Lipoprotein(a) [Lp(a)] is a highly heritable cardiovascular risk factor. Although discovered more than 50 years ago, Lp(a) has recently re-emerged as a major focus in the fields of lipidology and preventive cardiology owing to findings from genetic studies and the possibility of lowering elevated plasma concentrations with new antisense therapy. Data from genetic, epidemiological and clinical studies have provided compelling evidence establishing Lp(a) as a causal risk factor for atherosclerotic cardiovascular disease...
September 6, 2017: Progress in Lipid Research
https://www.readbyqxmd.com/read/28884604/novel-treatment-options-for-the-management-of-heterozygous-familial-hypercholesterolemia
#4
Georgios Polychronopoulos, Konstantinos Tziomalos
Even though statins represent the mainstay of treatment of heterozygous familial hypercholesterolemia (FH), their low-density lipoprotein cholesterol (LDL-C) lowering efficacy is finite and most patients with FH will not achieve LDL-C targets with statin monotherapy. Addition of ezetimibe with or without bile acid sequestrants will also not lead to treatment goals in many of these patients, particularly in those with established cardiovascular disease. In this selected subgroup of the FH population, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide substantial reductions in LDL-C levels, reduce cardiovascular morbidity and appear to be safe...
September 8, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28792970/targeting-hepatic-heparin-binding-egf-like-growth-factor-hb-egf-induces-anti-hyperlipidemia-leading-to-reduction-of-angiotensin-ii-induced-aneurysm-development
#5
Seonwook Kim, Lihua Yang, Seongu Kim, Richard G Lee, Mark J Graham, Judith A Berliner, Aldons J Lusis, Lei Cai, Ryan E Temel, Debra L Rateri, Sangderk Lee
OBJECTIVE: The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model. APPROACH AND RESULTS: Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28716988/blood-pressure-lowering-and-safety-improvements-with-liver-angiotensinogen-inhibition-in-models-of-hypertension-and-kidney-injury
#6
Adam E Mullick, Steve T Yeh, Mark J Graham, Jeffery A Engelhardt, Thazha P Prakash, Rosanne M Crooke
Uncontrolled hypertension is an important contributor to cardiovascular disease. Despite the armamentarium of antihypertensive treatments, there remains a need for novel agents effective in individuals who cannot reach acceptable blood pressure levels. Inhibitors targeting the renin-angiotensin-aldosterone system (RAAS) are widely used but may not optimally inhibit RAAS and demonstrate an acceptable safety profile. Experiments were conducted to characterize a series of AGT (angiotensinogen) antisense oligonucleotides (ASOs) and compare their efficacy and tolerability to traditional RAAS blockade...
September 2017: Hypertension
https://www.readbyqxmd.com/read/28670289/non-coding-rna-contribution-to-thoracic-and-abdominal-aortic-aneurysm-disease-development-and-progression
#7
REVIEW
Yuhuang Li, Lars Maegdefessel
Multiple research groups have started to uncover the complex genetic and epigenetic machinery necessary to maintain cardiovascular homeostasis. In particular, the key contribution of non-coding RNAs (ncRNAs) in regulating gene expression has recently received great attention. Aneurysms in varying locations of the aorta are defined as permanent dilations, predisposing to the fatal consequence of rupture. The characteristic pathology of an aneurysm is characterized by progressive vessel wall dilation, promoted by dying vascular smooth muscle cells and limited proliferation, as well as impaired synthesis and degradation of extracellular matrix components, which at least partially is the result of transmural inflammation and its disruptive effect on vessel wall homeostasis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28629892/engineered-myocardium-model-to-study-the-roles-of-hif-1%C3%AE-and-hif1a-as1-in-paracrine-only-signaling-under-pathological-level-oxidative-stress
#8
Aylin Acun, Pinar Zorlutuna
Studying heart tissue is critical for understanding and developing treatments for cardiovascular diseases. In this work, we fabricated precisely controlled and biomimetic engineered model tissues to study how cell-cell and cell-matrix interactions influence myocardial cell survival upon exposure to pathological level oxidative stress. Specifically, the interactions of endothelial cells (ECs) and cardiomyocytes (CMs), and the role of hypoxia inducible factor-1α (HIF-1α), with its novel alternative regulator, HIF-1α antisense RNA1 (HIF1A-AS1), in these interactions were investigated...
August 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28595549/apoc-iii-antisense-oligonucleotides-a-new-option-for-the-treatment-of-hypertriglyceridemia
#9
Joel Schmitz, Ioanna Gouni-Berthold
Elevated triglyceride levels (higher than ~1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apoC-III) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. Loss of function mutations in the gene encoding apoC-III (APOC3) are associated with low triglyceride levels and a decreased risk for cardiovascular disease (CVD) while overexpression of APOC3 is associated with hypertriglyceridemia. Although many drugs such as fibrates, statins and omega-3 fatty acids modestly decrease triglyceride levels (and apoC-III concentrations), there are many patients who still have severe hypertriglyceridemia and are at increased risk for pancreatitis and potentially for CVD...
June 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28550025/30-years-of-the-mineralocorticoid-receptor-mineralocorticoid-receptor-null-mice-informing-cell-type-specific-roles
#10
REVIEW
Timothy J Cole, Morag J Young
The mineralocorticoid receptor (MR) mediates the actions of two important adrenal corticosteroid hormones, aldosterone and cortisol. The cell signalling roles of the MR in vivo have expanded enormously since the cloning of human MR gene 30 years ago and the first MR gene knockout in mice nearly 20 years ago. Complete ablation of the MR revealed important roles postnatally for regulation of kidney epithelial functions, with MR-null mice dying 1-2 weeks postnatally from renal salt wasting and hyperkalaemia, with elevated plasma renin and aldosterone...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28538111/cardiovascular-and-metabolic-effects-of-angptl3-antisense-oligonucleotides
#11
RANDOMIZED CONTROLLED TRIAL
Mark J Graham, Richard G Lee, Teresa A Brandt, Li-Jung Tai, Wuxia Fu, Raechel Peralta, Rosie Yu, Eunju Hurh, Erika Paz, Bradley W McEvoy, Brenda F Baker, Nguyen C Pham, Andres Digenio, Steven G Hughes, Richard S Geary, Joseph L Witztum, Rosanne M Crooke, Sotirios Tsimikas
BACKGROUND: Epidemiologic and genomewide association studies have linked loss-of-function variants in ANGPTL3, encoding angiopoietin-like 3, with low levels of plasma lipoproteins. METHODS: We evaluated antisense oligonucleotides (ASOs) targeting Angptl3 messenger RNA (mRNA) for effects on plasma lipid levels, triglyceride clearance, liver triglyceride content, insulin sensitivity, and atherosclerosis in mice. Subsequently, 44 human participants (with triglyceride levels of either 90 to 150 mg per deciliter [1...
July 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28527325/dyslipidemia-management-update
#12
REVIEW
Yingzi Chang, Jacques Robidoux
Association of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) is well established. Reducing low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein-cholesterol (HDL-C) have been the therapeutic targets to reduce the risk of ASCVD. Cholesterol-lowering medications have been used to provide both primary and secondary prevention of ASCVD for many years by reducing the absorption and reabsorption, promoting excretion, or decreasing the synthesis of cholesterol. Within the past five years, several new classes of cholesterol-lowering drugs have been tested and approved for patients with hypercholesterolemia that are not well controlled by conventional therapy (ezetimibe, bile-acid sequestrants, and statins)...
April 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28408313/preventing-cardiovascular-heart-disease-promising-nutraceutical-and-non-nutraceutical-treatments-for-cholesterol-management
#13
REVIEW
T P Johnston, T A Korolenko, M Pirro, A Sahebkar
Hypercholesterolemia is one of the major risk factors for the development of cardiovascular disease. Atherosclerosis resulting from hypercholesterolemia causes many serious cardiovascular diseases. Statins are generally accepted as a treatment of choice for lowering low-density lipoprotein (LDL) cholesterol, which reduces coronary heart disease morbidity and mortality. Since statin use can be associated with muscle problems and other adverse symptoms, non-adherence and discontinuation of statin therapy often leads to inadequate control of plasma cholesterol levels and increased cardiovascular risk...
June 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28368771/investigational-therapies-for-hypercholesterolemia
#14
REVIEW
Gerald H Tomkin, Daphne Owens
Cardiovascular morbidity and mortality are of increasing concern, not only to patients but also to the health care profession and service providers. The preventative benefit of treatment of dyslipidaemia is unquestioned but there is a large, so far unmet need to improve clinical outcome. There are exciting new discoveries of targets that may translate into improved clinical outcome. Areas covered: This review highlights some new pathways in cholesterol and triglyceride metabolism and examines new targets, new drugs and new molecules...
May 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28365054/lipid-metabolism-and-emerging-targets-for-lipid-lowering-therapy
#15
REVIEW
Daniel Gaudet, Jean-Philippe Drouin-Chartier, Patrick Couture
Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality worldwide, and dyslipidemia constitutes a major risk factor for CVD and premature atherosclerosis. Therapies to reduce the plasma levels of atherogenic lipoproteins are well established interventions that decrease CVD risk. However, treatment of dyslipidemia with the most widely used lipid-lowering drugs (ie, statins and ezetimibe) often fails to protect a significant proportion of patients from cardiovascular risk. The development of several novel therapies to treat lipid-related disorders and their associated risks is ongoing and includes the following: (1) reducing plasma levels of atherogenic lipoproteins using proprotein convertase subtilisin/kexin type 9 inhibitors, antisense inhibitors of Apolipoprotein (Apo)(a), microsomal triglyceride transfer protein inhibitors, antisense oligonucleotides of ApoB for inhibiting very low-density lipoprotein production, and inhibitors of angiopoietin-like protein 3 or ApoC-III for triglyceride-rich lipoprotein management upstream of low-density lipoprotein production as well as gene replacement therapy to improve low-density lipoprotein and triglyceride-rich lipoprotein clearance; and (2) emerging therapies that target high-density lipoprotein (HDL) and reverse cholesterol transport using cholesteryl ester transfer protein inhibitors, HDL peptide mimetics, and autologous infusion of pre-β HDLs...
July 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28329241/lipoprotein-a-the-revenant
#16
Baris Gencer, Florian Kronenberg, Erik S Stroes, François Mach
In the mid-1990s, the days of lipoprotein(a) [Lp(a)] were numbered and many people would not have placed a bet on this lipid particle making it to the next century. However, genetic studies brought Lp(a) back to the front-stage after a Mendelian randomization approach used for the first time provided strong support for a causal role of high Lp(a) concentrations in cardiovascular disease and later also for aortic valve stenosis. This encouraged the use of therapeutic interventions to lower Lp(a) as well numerous drug developments, although these approaches mainly targeted LDL cholesterol, while the Lp(a)-lowering effect was only a 'side-effect'...
May 21, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28315297/paxillin-genes-and-actomyosin-contractility-regulate-myotome-morphogenesis-in-zebrafish
#17
Andrew E Jacob, Jeffrey D Amack, Christopher E Turner
Paxillin (Pxn) is a key adapter protein and signaling regulator at sites of cell-extracellular matrix (ECM) adhesion. Here, we investigated the role of Pxn during vertebrate development using the zebrafish embryo as a model system. We have characterized two Pxn genes, pxna and pxnb, in zebrafish that are maternally supplied and expressed in multiple tissues. Gene editing and antisense gene knockdown approaches were used to uncover Pxn functions during zebrafish development. While mutation of either pxna or pxnb alone did not cause gross embryonic phenotypes, double mutants lacking maternally supplied pxna or pxnb displayed defects in cardiovascular, axial, and skeletal muscle development...
May 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28287809/increased-risk-of-chd-in-the-presence-of-rs7865618-a-allele-tehran-lipid-and-glucose-study
#18
Samaneh Matoo, Mohammad Sadegh Fallah, Maryam Sadat Daneshpour, Reyhaneh Mousavi, Bahareh Sedaghati Khayat, Mandana Hasanzad, Fereidoun Azizi
BACKGROUND: Recent genome-wide association studies (GWAS) in European populations have indicated that the rs12526453 polymorphism located in phosphatase and actin regulator 1 gene (PHACTR1), mapping to chromosome 6p24 and rs7865618 polymorphism in the cyclin-dependent kinase inhibitor B antisense RNA 1 gene (CDKN2B-AS1) on 9p21.3 are associated with coronary heart disease (CHD). This study was carried out to investigate the association of these polymorphisms and CHD in an Iranian population...
March 2017: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/28243616/data-on-genotypic-distribution-and-linkage-disequilibrium-of-several-anril-polymorphisms-in-hemodialysis-patients
#19
A Arbiol-Roca, A Padró-Miquel, M Hueso, E Navarro, P Alía-Ramos, M T González-Álvarez, I Rama, J Torras, J M Grinyó, J M Cruzado, N Lloberas
A long non-coding RNA called ANRIL located on chromosome 9p21.3 has been identified as a novel genetic factor associated with cardiovascular disease. Investigation of several single nucleotide polymorphisms (SNPs) of Noncoding Antisense RNA in the INK4 Locus (ANRIL) gene are of particular interest. This article reports data related to the research article entitled: "Association of ANRIL gene polymorphisms with major adverse cardiovascular events in hemodialysis patients" (Arbiol-Roca et al. [1]). Data presented show the genotypic distribution of four selected ANRIL SNPs: rs10757278, rs4977574, rs10757274 and rs6475606 in a cohort constituted by 284 hemodialysis patients...
April 2017: Data in Brief
https://www.readbyqxmd.com/read/28209220/very-low-density-lipoprotein-associated-apolipoproteins-predict-cardiovascular-events-and-are-lowered-by-inhibition%C3%A2-of%C3%A2-apoc-iii
#20
Raimund Pechlaner, Sotirios Tsimikas, Xiaoke Yin, Peter Willeit, Ferheen Baig, Peter Santer, Friedrich Oberhollenzer, Georg Egger, Joseph L Witztum, Veronica J Alexander, Johann Willeit, Stefan Kiechl, Manuel Mayr
BACKGROUND: Routine apolipoprotein (apo) measurements for cardiovascular disease (CVD) are restricted to apoA-I and apoB. Here, the authors measured an unprecedented range of apolipoproteins in a prospective, population-based study and relate their plasma levels to risk of CVD. OBJECTIVES: This study sought to measure apolipoproteins directly by mass spectrometry and compare their associations with incident CVD and to obtain a system-level understanding of the correlations of apolipoproteins with the plasma lipidome and proteome...
February 21, 2017: Journal of the American College of Cardiology
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