Korean J Physiol Pharmacol.  2023 Jul;27(4):289-298. 10.4196/kjpp.2023.27.4.289.

Roles of non-coding RNAs in intercellular crosstalk in cardiovascular diseases

• Lim YH
• Kim YK

• KMID: 2544131
• DOI: http://doi.org/10.4196/kjpp.2023.27.4.289

Abstract

Complex diseases including cardiovascular disease are caused by a combination of the alternation of many genes and the influence of environments. Recently, non-coding RNAs (ncRNAs) have been shown to be involved in diverse diseases, and the functions of various ncRNAs have been reported. Many researchers have elucidated the mechanisms of action of these ncRNAs at the cellular level prior to in vivo and clinical studies of the diseases. Due to the characteristics of complex diseases involving intercellular crosstalk, it is important to study communication between multiple cells. However, there is a lack of literature summarizing and discussing studies of ncRNAs involved in intercellular crosstalk in cardiovascular diseases. Therefore, this review summarizes recent discoveries in the functional mechanisms of intercellular crosstalk involving ncRNAs, including microRNAs, long non-coding RNAs, and circular RNAs. In addition, the pathophysiological role of ncRNAs in this communication is extensively discussed in various cardiovascular diseases.

Keyword

Cardiovascular diseases; Coculture techniques; Exosomes; Extracellular vesicles; RNA, Untranslated

Figure

• 

  Fig. 1 Co-culture systems. (A) Indirect co-culture model. Intercellular crosstalk is mediated through factors secreted from cells. In a model, each cell type is cultured separately, and the supernatant cultivated with one cell type (conditioned medium) is applied to the other cell type. Otherwise, each cell type is cultured separative at the same culture well through the transwell chamber and the secreted factors (cytokines, chemokines, growth factors, and extracellular vesicles) are exchanged. (B) Direct co-culture model. Both cells are cultured together in the same culture well for interaction through secreted factors and adhesion molecules (ICAM-1, VCAM-1, E-selectin, and receptors) allowing cell-to-cell contact. Two different types of adherent cells (vascular smooth muscle cells or endothelial cells), or both adherent and suspension cells (immune cells), are cultured together. Otherwise, each cell type attached to the opposite sides of the permeable membrane of the transwell chamber is allowed to interact through contact and to exchange secreted factor. (C) Gel scaffold 3D co-culture model. An extracellular matrix (ECM) is used to construct a gel scaffold in a culture well or transwell chamber. Through the ECM layer, compartments are divided between different cell types, and intercellular crosstalk and cell migration can be observed through this layer. ICAM-1, intercellular adhesion molecule 1; VCAM-1, vascular cell adhesion molecule 1; 3D, three-dimensional.

• 

  Fig. 2 The intercellular crosstalk and non-coding RNAs (ncRNAs) in diseases. ncRNAs are differentially expressed by various cellular stresses that cause disease, and they transmit signals to other cells in two major ways. First, ncRNAs are directly delivered from donor cells to recipient cells by extracellular vesicles such as exosomes and microvesicles (red arrow). These delivered ncRNAs interfere with the protein translation of target mRNAs (miRNA) or regulate the expression of other genes by binding to RNA-binding proteins or miRNAs (lncRNA and circRNA). In another way, ncRNAs indirectly affect recipient cells by regulating the expression of secreted factors (cytokines, chemokines, and growth factors) or cell adhesion molecules (ICAM-1, VCAM-1, E-selectin, and receptors) in donor cells (blue arrow). miRNA, microRNA; lncRNA, long non-coding RNA; circRNA, circular RNA; MVB, multivesicular body; Ang II, angiotensin II; I/R injury, ischemia-reperfusion injury; oxLDL, oxidized low density lipoprotein; TNF-α, tumor necrosis factor-α; ILs, interleukins; MMPs, matrix metalloproteinases; GFs, growth factors; sICAM-1, soluble intercellular adhesion molecule-1; sVCAM-1, soluble vascular cell adhesion molecule-1.

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