HDL and microRNA therapeutics in cardiovascular disease

Wang

et al. 2020

IJMS

Epidemiological results revealed that there is an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and risks of atherosclerotic cardiovascular disease (ASCVD). Mounting evidence supports that HDLs are atheroprotective, therefore, many therapeutic approaches have been developed to increase HDL cholesterol (HDL-C) levels. Nevertheless, HDL-raising therapies, such as cholesteryl ester transfer protein (CETP) inhibitors, failed to ameliorate cardiovascular outcomes in clinical trials, thereby casting doubt on the treatment of cardiovascular disease (CVD) by increasing HDL-C levels. Therefore, HDL-targeted interventional studies were shifted to increasing the number of HDL particles capable of promoting ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux. One such approach was the development of reconstituted HDL (rHDL) particles that promote ABCA1-mediated cholesterol efflux from lipid-enriched macrophages. Here, we explore the manipulation of rHDL nanoparticles as a strategy for the treatment of CVD. In addition, we discuss technological capabilities and the challenge of relating preclinical in vivo mice research to clinical studies. Finally, by drawing lessons from developing rHDL nanoparticles, we also incorporate the viabilities and advantages of the development of a molecular imaging probe with HDL nanoparticles when applied to ASCVD, as well as gaps in technology and knowledge required for putting the HDL-targeted therapeutics into full gear.

Section: Delivery Of Oligonucleotides Using Rhdl Nanoparticlesmentioning

confidence: 99%

Roles of Reconstituted High-Density Lipoprotein Nanoparticles in Cardiovascular Disease: A New Paradigm for Drug Discovery

Wang

et al. 2020

IJMS

“…For more detailed reviews on HDL metabolism, see references [3,8,9]. Apart from cholesterol transport, HDL particles act as carriers for vitamins, proteins or nucleic acids, thus playing a vital role in intercellular communication [10,11,12] Moreover, HDL shows anti-inflammatory and antioxidant properties by inhibiting lipoprotein oxidation by metabolizing lipid hydroperoxides [13,14]. These inherent features of HDL are extremely important considering artificial HDL particles as pharmaceutical nanocarriers.…”

Section: Lipoprotein Metabolism and Coronary Heart Diseasementioning

confidence: 99%

“…In the following, AuNP core functionalized rHDL were also successful in the delivery of therapeutic short interference RNA (siRNA) [134,135]. Similarly, rHDL particles showed high potential for the delivery of microRNA (miRNA) for gene silencing and for the modification of gene expression profiles [10,11,12]. Native HDL have been identified to function as endogenous carriers for miRNAs in circulation and as transporter for miRNAs to recipient cells in the setting of intercellular communication [11,136].…”

Section: Rhdl As Delivery Systems In Therapy and Diagnosis Of Cvdsmentioning

confidence: 99%

Artificial High Density Lipoprotein Nanoparticles in Cardiovascular Research

2019

Lipoproteins are endogenous nanoparticles which are the major transporter of fats and cholesterol in the human body. They play a key role in the regulatory mechanisms of cardiovascular events. Lipoproteins can be modified and manipulated to act as drug delivery systems or nanocarriers for contrast agents. In particular, high density lipoproteins (HDL), which are the smallest class of lipoproteins, can be synthetically engineered either as nascent HDL nanodiscs or spherical HDL nanoparticles. Reconstituted HDL (rHDL) particles are formed by self-assembly of various lipids and apolipoprotein AI (apo-AI). A variety of substances including drugs, nucleic acids, signal emitting molecules, or dyes can be loaded, making them efficient nanocarriers for therapeutic applications or medical diagnostics. This review provides an overview about synthesis techniques, physicochemical properties of rHDL nanoparticles, and structural determinants for rHDL function. We discuss recent developments utilizing either apo-AI or apo-AI mimetic peptides for the design of pharmaceutical rHDL formulations. Advantages, limitations, challenges, and prospects for clinical translation are evaluated with a special focus on promising strategies for the treatment and diagnosis of atherosclerosis and cardiovascular diseases.

“…A present, microRNAs are more extensively studied than circRNAs. Certain miRNAs have been reported to be involved in cardiovascular diseases and were demonstrated to be closely associated with EH (12,13). Zheng et al (14) suggested that miR-155 levels are negatively correlated with blood pressure.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA hsa_circ_0014243 may serve as a diagnostic biomarker for essential hypertension

Zheng

Bao

et al. 2018

Exp Ther Med

Circular RNAs (circRNAs) have a great potential as clinical biomarkers; however, specific circRNAs with a diagnostic value for essential hypertension (EH) largely remain to be identified. In the present study, the potential application of Homo sapiens (hsa)_circ_0014243, which was identified to be significantly upregulated in whole blood samples of EH patients in a previous microarray profiling study by our group, in the diagnosis of EH was evaluated. Reverse transcription-quantitative polymerase chain reaction analysis was performed to determine the expression levels of hsa_circ_0014243 and hsa-microRNA (miR)-10a-5p in a total of 178 blood samples collected from 89 healthy controls and 89 patients diagnosed with EH. Divergent primers were designed for circRNAs, while conventional primers were used for miRs. Independent-samples t-tests and bivariate correlation analyses were performed to analyze the association between clinical factors influencing EH and hsa_circ_0014243 expression levels. A receiver operating characteristics (ROC) curve was generated to estimate the diagnostic value of hsa_circ_0014243 for EH. Finally, the expression levels of circRNAs and miRNAs were combined to propose a possible prediction model for EH. The results indicated that hsa_circ_0014243 was upregulated in whole blood samples of EH patients compared with that in the controls (P<0.001). Furthermore, the relative expression levels of hsa_circ_0014243 (Δ quantification cycle) were identified to be significantly correlated with age (r=−0.259, P<0.001), high-density lipoprotein levels (r=0.196, P=0.009) and glucose levels (r=−0.204, P=0.006). The area under the ROC curve (AUC) of the model using hsa_circ_0014243 as a predictor was 0.732. Of note, the AUC increased to 0.781 when hsa_circ_0014243 levels were combined with hsa-miR-10a-5p levels as predictors. The present results suggest that hsa_circ_0014243 has a crucial role in the genesis and development of EH, and presents a certain diagnostic capability for EH.