Purine metabolism in the circulatory system yields uric acid as its final oxidation product, which is
believed to be linked to the development of gout and kidney stones. Hyperuricemia is closely correlated with
cardiovascular disease, metabolic syndrome, and chronic kidney disease, as attested by the epidemiological and
empirical research. In this review, we summarize the recent knowledge about hyperuricemia, with a special focus
on its physiology, epidemiology, and correlation with cardiovascular disease. This review also discusses the possible
positive effects of treatment to reduce urate levels in patients with cardiovascular disease and hyperuricemia,
which may lead to an improved clinical treatment plan.
Oxidized low-density lipoprotein (oxLDL) induces macrophage inflammation and lipid uptake, and serves important roles in the development of atherosclerosis. The long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (neat1) has two isoforms; the longer isoform, neat1_2, mediates the formation of subnuclear structures called paraspeckles. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and RNA protein immunoprecipitation (RIP), revealed that oxLDL induced paraspeckle formation in the THP-1 cell line. Additionally, the nuclear factor-κB and p38 pathways were observed to be involved in neat1 transcription. To investigate the role of paraspeckles in oxLDL-induced macrophage inflammation and lipid uptake, macrophages were transfected with small interfering RNAs against NEAT1, NEAT1_2, non-POU domain-containing octamer-binding (NONO) and splicing factor proline and glutamine rich prior to oxLDL incubation. In addition, inflammation-associated pathways and scavenger receptors were analyzed by performing western blotting and RT-qPCR. p65 phosphorylation and cluster of differentiation 36 (CD36) were demonstrated to serve roles in paraspeckle-mediated inflammation and lipid uptake, respectively. To determine the underlying mechanism, RIP was preformed, which revealed that NONO binds CD36 mRNA to decrease its expression. In conclusion, oxLDL induced neat1_2-mediated paraspeckle formation. Paraspeckles participate in oxLDL-induced macrophage inflammation and lipid uptake by regulating p65 phosphorylation and CD36 mRNA.
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