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Total 572 results found since Jan 2013.

The Promise of PCSK9 and Lipoprotein(a) as Targets for Gene Silencing Therapies
Clin Ther. 2023 Jul 29:S0149-2918(23)00258-8. doi: 10.1016/j.clinthera.2023.07.008. Online ahead of print.ABSTRACTPURPOSE: High plasma concentrations of LDL and lipoprotein(a) (Lp[a]) are independent and causal risk factors for atherosclerotic cardiovascular disease (ASCVD). There is an unmet therapeutic need for high-risk patients with elevated levels of LDL-C and/or Lp(a). Recent advances in the development of nucleic acids for gene silencing (ie, triantennary N-acetylgalactosamine conjugated antisense-oligonucleotides [ASOs] and small interfering RNA [siRNA]) targeting proprotein convertase subtilisin/kexin type 9 (PCSK...
Source: Clinical Therapeutics - July 31, 2023 Category: Drugs & Pharmacology Authors: Dick C Chan Gerald F Watts Source Type: research

Genome-wide Screen for ApoA-I Secretion Lipids
Control of plasma cholesterol levels is a major therapeutic strategy for management of coronary artery disease (CAD). Although reducing LDL cholesterol (LDL-c) levels decreases morbidity and mortality, this therapeutic intervention only translates into a 25–40% reduction in cardiovascular events. Epidemiological studies have shown that a high LDL-c level is not the only risk factor for CAD; low HDL cholesterol (HDL-c) is an independent risk factor for CAD. Apolipoprotein A-I (ApoA-I) is the major protein component of HDL-c that mediates reverse cholesterol transport from tissues to the liver for excretion. Therefore, inc...
Source: Journal of Biological Chemistry - March 1, 2013 Category: Chemistry Authors: Miles, R. R., Perry, W., Haas, J. V., Mosior, M. K., N'Cho, M., Wang, J. W. J., Yu, P., Calley, J., Yue, Y., Carter, Q., Han, B., Foxworthy, P., Kowala, M. C., Ryan, T. P., Solenberg, P. J., Michael, L. F. Tags: Lipids Source Type: research

Involvement of cdc42/Rho kinase in ApoA‐I‐mediated cholesterol efflux through interaction between cytosolic lipid‐protein particles and microtubules in rat astrocytes
We examined the involvement of cdc42 and Rho kinase in intracellular cholesterol transport for release of cholesterol after the interaction between apoA‐I and ABCA1 in astrocytes. Exogenously added apoA‐I increased the GTP‐bound form of cdc42 and enhanced Rho kinase activity in rat astrocytes. Suppression of ABCA1 expression by siRNA substantially repressed both cellular level of GTP‐bound cdc42 and Rho kinase activity, indicating that these reactions require ABCA1. ApoA‐I‐mediated lipid release and Rho kinase activation were inhibited by not only Rho kinase inhibitor but also cdc42 siRNA. These findings sugges...
Source: Journal of Neuroscience Research - January 20, 2014 Category: Neuroscience Authors: Alireza Kheirollah, Yuko Nagayasu, Hiroshi Ueda, Shinji Yokoyama, Makoto Michikawa, Jin‐ichi Ito Tags: Research Article Source Type: research

Renalase is a novel target gene of hypoxia-inducible factor-1 in protection against cardiac ischaemia-reperfusion injury
Conclusion These findings have revealed renalase as a novel target gene of HIF-1α in protection against myocardial I/R injury, which provided a basis for therapeutic strategies for enhancing cardiomyocyte survival in patients associated with ischaemic heart diseases.
Source: Cardiovascular Research - January 16, 2015 Category: Cardiology Authors: Du, M., Huang, K., Huang, D., Yang, L., Gao, L., Wang, X., Huang, D., Li, X., Wang, C., Zhang, F., Wang, Y., Cheng, M., Tong, Q., Qin, G., Huang, K., Wang, L. Tags: Cardiac biology and remodelling Source Type: research

Study on Regulation of Low Density Lipoprotein Cholesterol Metabolism using PCSK9 Gene Silencing: A computational Approach.
Abstract Combating and preventing abnormality in lipid metabolism becomes a pivotal criterion for research. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein; it promotes the degradation of low-density lipoprotein receptors (LDL-R) and hence increases LDL-C levels. Silencing the gene PCSK9 at post-transcriptional level with the help of small interfering Ribo nucleic acid (siRNA) gives a new insight and a novel therapeutic way to regulate LDL-C metabolism. Designing and selecting an efficient siRNA for silencing PCSK9 at post transcriptional level through computational approach. We have...
Source: Bioinformation - August 17, 2018 Category: Bioinformatics Authors: Vijayaraghavan B, Danabal K, Padmanabhan G, Ramanathan K Tags: Bioinformation Source Type: research

Silencing of GPR82 with Interference RNA Improved Metabolic Profiles in Rats with High Fructose Intake
Metabolic syndrome (MS) is a clinical condition, constituted by alterations that lead to the onset of type II diabetes and cardiovascular disease. It has been reported that orphan G-protein-coupled receptor 82 (GPR82) participates in metabolic processes. The aim of this study was to evaluate the  function of GPR82 in MS using a small interfering RNA (siRNA) against this receptor. We used Wistar rats of 10–12 weeks of age fed with a high-fructose solution (70%) for 9 weeks to induce MS. Subsequently, the rats were treated with an intrajugular dose of an siRNA against GPR82 and the effects were evaluated on day 3 and 7 af...
Source: Journal of Vascular Research - July 2, 2019 Category: Research Source Type: research

Characterization of Zika Virus Endocytic Pathways in Human Glioblastoma Cells
Zika virus (ZIKV) infections can cause microcephaly and neurological disorders. However, the early infection events of ZIKV in neural cells remain to be characterized. Here, by using a combination of pharmacological and molecular approaches and the human glioblastoma cell T98G as a model, we first observed that ZIKV infection was inhibited by chloroquine and NH4Cl, indicating a requirement of low intracellular pH. We further showed that dynamin is required as the ZIKV entry was affected by the specific inhibitor dynasore, small interfering RNA (siRNA) knockdown of dynamin, or by expressing the dominant-negative K44A mutant...
Source: Frontiers in Microbiology - March 5, 2020 Category: Microbiology Source Type: research

SCAP Mediated GDF15-Induced Invasion and EMT of Esophageal Cancer
Conclusions: We demonstrated that SCAP mediated GDF15-induced the invasion and metastasis of EC by regulating cholesterol metabolism. In addition, GDF15 was shown to be a direct target of miR-1324.
Source: Frontiers in Oncology - October 5, 2020 Category: Cancer & Oncology Source Type: research

From traditional pharmacological towards nucleic acid-based therapies for cardiovascular diseases
AbstractNucleic acid-based therapeutics are currently developed at large scale for prevention and management of cardiovascular diseases (CVDs), since: (i) genetic studies have highlighted novel therapeutic targets suggested to be causal for CVD; (ii) there is a substantial recent progress in delivery, efficacy, and safety of nucleic acid-based therapies; (iii) they enable effective modulation of therapeutic targets that cannot be sufficiently or optimally addressed using traditional small molecule drugs or antibodies. Nucleic acid-based therapeutics include (i) RNA-targeted therapeutics for gene silencing; (ii) microRNA-mo...
Source: European Heart Journal - April 29, 2020 Category: Cardiology Source Type: research

CROT (Carnitine O-Octanoyltransferase) Is a Novel Contributing Factor in Vascular Calcification via Promoting Fatty Acid Metabolism and Mitochondrial Dysfunction.
CONCLUSIONS: CROT is a novel contributing factor in vascular calcification via promoting fatty acid metabolism and mitochondrial dysfunction, as such CROT inhibition has strong potential as an antifibrocalcific therapy. PMID: 33356393 [PubMed - as supplied by publisher]
Source: Arteriosclerosis, Thrombosis and Vascular Biology - December 24, 2020 Category: Cardiology Authors: Okui T, Iwashita M, Rogers MA, Halu A, Atkins SK, Kuraoka S, Abdelhamid I, Higashi H, Ramsaroop A, Aikawa M, Singh SA, Aikawa E Tags: Arterioscler Thromb Vasc Biol Source Type: research

Effect of inclisiran, the small-interfering RNA against proprotein convertase subtilisin/kexin type 9, on platelets, immune cells, and immunological biomarkers: a pre-specified analysis from ORION-1
Conclusion  In this pre-specified safety analysis of ORION-1 for the siRNA therapeutic inclisiran, no adverse effects on measures of inflammation or immune activation nor adverse effects on platelets or clinical immunogenicity AEs were observed over at least 6-month treatment. These safety findings in the largest analysis of an RNAi study in humans to date provide strong reassurance about the safety of inclisiran and the potential of cardiovascular RNA-targeted therapies.
Source: Cardiovascular Research - April 3, 2020 Category: Cardiology Source Type: research

ANGPTL3 and Apolipoprotein C-III as Novel Lipid-Lowering Targets
AbstractPurpose of ReviewDespite significant progress in plasma lipid lowering strategies, recent clinical trials highlight the existence of residual cardiovascular risk. Angiopoietin-like protein 3 (ANGPTL3) and apolipoprotein C-III (Apo C-III) have been identified as novel lipid-lowering targets.Recent FindingsApo C-III and ANGPTL3 have emerged as novel regulators of triglyceride (TG) and low-density lipoprotein-cholesterol (LDL-C) levels. ANGPTL3 is an inhibitor of lipoprotein lipase (LPL), reducing lipolysis of Apo B-containing lipoproteins. Loss-of-functionANGPLT3 mutations are associated with reduced plasma cholester...
Source: Current Atherosclerosis Reports - March 10, 2021 Category: Cardiology Source Type: research

The Role of RNA-Targeted Therapeutics to Reduce ASCVD Risk: What Have We Learned Recently?
AbstractPurpose of ReviewTo discuss advances on the RNA-targeted therapies to treat dyslipidemia with the aim of reducing atherosclerotic cardiovascular disease (ASCVD).Recent FindingsGenetic studies have paved the way for therapies that reduce translation of proteins that play causal roles in dyslipidemia and atherosclerosis like proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B-100 (apoB), apolipoprotein(a) [apo(a)], apolipoprotein C3 (apoC3), and angiopoietin-like 3 (ANGPTL3). Either antisense oligonucleotide (ASO) therapies and small interfering RNA (siRNA) molecules inhibit protein synthesis and ...
Source: Current Atherosclerosis Reports - June 19, 2021 Category: Cardiology Source Type: research