RNA Therapeutics for the Cardiovascular System

Circulation, Journal Year: 2024, Volume and Issue: 149(9), P. 707 - 716

Published: Feb. 26, 2024

RNA therapeutics hold significant promise in the treatment of cardiovascular diseases. RNAs are biologically diverse and functionally specific can be used for gain- or loss-of-function purposes. The effectiveness mRNA-based vaccines recent COVID-19 pandemic has undoubtedly proven benefits an RNA-based approach. therapies becoming more common as a modality disease. This is most evident hypertension where several small interfering RNA–based drugs have to effective managing high blood pressure clinical trials. As befits rapidly burgeoning field, there interest other classes RNA. Revascularization infarcted heart through mRNA drug under investigation. technology may provide platform expression paracrine factors myocardial protection regeneration. Emergent technologies on basis microRNAs gene editing tackling complex diseases novel fashion. offers hope permanent cures monogenic diseases, long-term control such essential hypertension, well. Likewise, proving regenerating cardiac muscle. aim this review overview current landscape describes large number molecules that exist with discussion development each type. In addition, also presents avenues future development.

Language: Английский

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Navigating the landscape of RNA delivery systems in cardiovascular disease therapeutics

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 208, P. 115302 - 115302

Published: April 3, 2024

Cardiovascular diseases (CVDs) stand as the leading cause of death worldwide, posing a significant global health challenge. Consequently, development innovative therapeutic strategies to enhance CVDs treatment is imperative. RNA-based therapies, encompassing non-coding RNAs, mRNA, aptamers, and CRISPR/Cas9 technology, have emerged promising tools for addressing CVDs. However, inherent challenges associated with RNA, such poor cellular uptake, susceptibility RNase degradation, capture by reticuloendothelial system, underscore necessity combining these therapies effective drug delivery systems. Various non-viral systems, including extracellular vesicles, lipid-based carriers, polymeric inorganic nanoparticles, well hydrogels, shown promise in enhancing efficacy RNA therapeutics. In this review, we offer an overview most relevant explored emphasize pivotal role systems augmenting their effectiveness. Additionally, discuss current status that hinder clinical translation.

Language: Английский

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Therapy for Hyperlipidemia

Medical Clinics of North America, Journal Year: 2024, Volume and Issue: 108(5), P. 881 - 894

Published: June 5, 2024

Language: Английский

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Lifestyle and Lipoprotein(a) Levels: Does a Specific Counseling Make Sense?

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(3), P. 751 - 751

Published: Jan. 28, 2024

Lipoprotein(Lp)(a) is a variant of low-density lipoprotein (LDL), bound to apolipoprotein B100, whose levels are associated with significant increase in the risk atherosclerosis-related cardiovascular events, but also aortic stenosis and atrial fibrillation. Since plasma Lp(a) commonly considered resistant lifestyle changes, we critically reviewed available evidence on effect weight loss, dietary supplements, physical activity this factor. In our review, observed that relevant body relatively high intake saturated fatty acids, consumption red wine, intense exercise seems be significantly lower levels. On contrary, foods rich trans-unsaturated acids increased With regard coenzyme Q10, L-Carnitine, flaxseed exert mild lowering Lp(a).

Language: Английский

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Drugs for dyslipidaemia: the legacy effect of the Scandinavian Simvastatin Survival Study (4S)

The Lancet, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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Association of familial ATTR amyloidosis and hyperlipoprotein(a)emia in a patient with spinal stenosis. A case report

Digital Diagnostics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Introduction: Transthyretin (ATTR) amyloidosis is a rare disease with cardiac involvement, peripheral nervous system and spinal stenosis. Elevated plasma lipoprotein(a) (Lpa) levels are recognized as significant risk factor for atherosclerotic cardiovascular cerebrovascular diseases. Currently, information on the relationship between ATTR Lpa very limited. Clinical case: A female patient had suffered from arterial hypertension an increase in blood pressure (BP) to 150/90 mmHg 5 years since age of 45. After suffering new coronavirus infection COVID-19 02.06 25.06.2021, began notice 290/150 mm Hg, stabbing pains left half chest lasting up 20-30 minutes without any connection physical activity, which relieved after taking Corvalol, pain cervical thoracic spine. Due antihypertensive therapy, stabilization at 110/70 Hg was noted. Further examination revealed dyslipidemia (low-density lipoprotein cholesterol 4.53 mmol/l), atherosclerosis extracranial parts brachiocephalic arteries stenosis right internal carotid artery 20%, hyperlipoprotein(a)emia 1.46 g/l (normal 0.5 g/l). Echocardiography ventricular wall thickening preserved ejection fraction, interatrial septum, mitral valve cusps. MRI spine canal level C5-6 - "red flag" amyloidosis. Genetic testing variant nucleotide sequence transthyretin gene (Chr18: 29171879 GA, p.Arg5His) heterozygous state her relatives. The issue specific antiamyloid therapy tafamidis considered, lipid-lowering prescribed. Conclusion. In patients syndrome thickening, even presence hypertension, comprehensive necessary timely diagnosis adequate amyloid cardiomyopathy. combination familial has been described first time.

Language: Английский

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Perspectives on early health economic evaluations of RNA therapies targeted at lipoprotein(a)

Current Opinion in Endocrinology Diabetes and Obesity, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Purpose of review Early health economic evaluations new medications are useful, as they consider the implications for services. We reviewed recent literature on expected clinical outcomes lowering elevated plasma lipoprotein(a) [Lp(a)] in secondary prevention, which is essential information effectiveness evaluations. a early evaluation RNA therapies targeted at Lp(a). Recent findings RNA-based therapies, if approved, would likely be used initially adults with established atherosclerotic cardiovascular disease (ASCVD) and very high Adults ASCVD have absolute risk recurrent events Lp(a) serves risk-enhancing factor. Potent prevention may associated significant relative reductions coronary heart or events; this needs confirmation currently ongoing future trials. One has estimated value olpasiran pelacarsen, various willingness-to-pay thresholds, compared standard-of-care prevention. Summary estimate longer-term benefits cost consequences medications. Existing casual evidence can best available evidence, while awaiting results from major

Language: Английский

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The Potential of RNA Therapeutics in Treating Cardiovascular Disease

Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Language: Английский

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Lipoprotein(a): Assessing the Current Knowledge and Gaps in Screening and Treatment—A Narrative Review

Journal of Cardiovascular Development and Disease, Journal Year: 2025, Volume and Issue: 12(5), P. 169 - 169

Published: April 26, 2025

Atherosclerotic cardiovascular disease (ASCVD) has long been screened using the traditional lipid profile, mainly focusing on LDL cholesterol. However, despite growing evidence supporting lipoprotein(a) [Lp(a)] as an independent risk factor involved in atherosclerosis, its clinical use remains limited. This review examines reasons behind limited of Lp(a) screening practice, assessing role risk, comparing it to markers and evaluating current assessment methods. It also explores existing emerging treatments, including gene-silencing therapies, for managing elevated levels. One four clinicians does not routinely check levels, which proves a lack awareness amongst them. The that are implied be cost is too high available treatments scarce. LDL, high-density lipoprotein (HDL) triglycerides, continues gold standard CV assessment. limitation practice significant variability apo(a) sizes, results from presence multiple isoforms determined by number kringle domains. structural diversity poses challenges standardizing measurement methods, affecting accuracy comparability results. While statins have minimal impact Lp(a), PCSK9-i lowers levels 20–25%, although this class prescribed primarily reason. Lastly, achieve greatest reduction still phase III trials, there need examine whether translates into benefits. These limitations should discourage further research, because ASCVD’s complexity requires more tailored approach. Current lipid-lowering therapy fails minority cases, evidenced new-onset events patients with well-controlled There future interventional studies assess really benefits, LDL.

Language: Английский

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Assessment of Apolipoprotein(a) Isoform Size Using Phenotypic and Genotypic Methods

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(18), P. 13886 - 13886

Published: Sept. 9, 2023

Apolipoprotein(a) (apo(a)) is the protein component that defines lipoprotein(a) (Lp(a)) particles and encoded by LPA gene. The apo(a) extremely heterogeneous in size due to copy number variations kringle-IV type 2 (KIV2) domains. In this review, we aim discuss role of genetics establishing Lp(a) as a risk factor for coronary heart disease (CHD) examining series molecular biology techniques aimed at identifying best strategy possible application clinical research practice, according current gold standard.

Language: Английский

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