RESUMO
Cardiovascular diseases, involving vasculopathy, cardiac dysfunction, or circulatory disturbance, have become the major cause of death globally and brought heavy social burdens. The complexity and diversity of the pathogenic factors add difficulties to diagnosis and treatment, as well as lead to poor prognosis of these diseases. MicroRNAs are short non-coding RNAs to modulate gene expression through directly binding to the 3'-untranslated regions of mRNAs of target genes and thereby to downregulate the protein levels post-transcriptionally. The multiple regulatory effects of microRNAs have been investigated extensively in cardiovascular diseases. MiR-223-3p, expressed in multiple cells such as macrophages, platelets, hepatocytes, and cardiomyocytes to modulate their cellular activities through targeting a variety of genes, is involved in the pathological progression of many cardiovascular diseases. It participates in regulation of several crucial signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B, insulin-like growth factor 1, nuclear factor kappa B, mitogen-activated protein kinase, NOD-like receptor family pyrin domain containing 3 inflammasome, and ribosomal protein S6 kinase B1/hypoxia inducible factor 1 α pathways to affect cell proliferation, migration, apoptosis, hypertrophy, and polarization, as well as electrophysiology, resulting in dysfunction of cardiovascular system. Here, in this review, we will discuss the role of miR-223-3p in cardiovascular diseases, involving its verified targets, influenced signaling pathways, and regulation of cell function. In addition, the potential of miR-223-3p as therapeutic target and biomarker for diagnosis and prediction of cardiovascular diseases will be further discussed, providing clues for clinicians.
RESUMO
Hyperkalemia is a major cause of on-site death in crush syndrome (CS), which is more severe and common in male victims. Anisodamine is a belladonna alkaloid and widely used in China for treatment of shock through activation of α7 nicotinic acetylcholine receptor (α7nAChR). The present work was designed to study the protective effect of anisodamine in CS and the possible role of estradiol involved. Male and ovariectomized female CS mice exhibited lower serum estradiol and insulin sensitivity, and higher potassium compared to the relative female controls at 6 h after decompression. There was no gender difference in on-site mortality in CS mice within 24 h after decompression. Serum estradiol increased with similar values in CS mice of both gender compared to that in normal mice. Anisodamine decreased serum potassium and increased serum estradiol and insulin sensitivity in CS mice, and methyllycaconitine, selective antagonist of α7nAChR, counteracted such effects of anisodamine. Treatment with anisodamine or estradiol increased serum estradiol and insulin sensitivity, decreased serum potassium and on-site mortality, and eliminated the difference in these parameters between CS mice received ovariectomy or its sham operation. Anisodamine could also increase blood pressure in CS rats within 3.5 h after decompression, which could also be attenuated by methyllycaconitine, without influences on heart rate. These results suggest that activation of α7nAChR with anisodamine could decrease serum potassium and on-site mortality in CS through estradiol-induced enhancement of insulin sensitivity.
