Table 3.
Experimental models of the effects of RA on the dedifferentiation of VSMCs.
| First Author (Year) | Experimental Model | Agent, Dose of Administration | Main Results | Other Results |
|---|---|---|---|---|
| Pan H. (2020) [52] | ROSA26ZsGreen1/+; Ldlr−/−; Myh11-CreERT2 mice | 10 μM ATRA for 72 h | • Attenuation of SEM cells transition • Suppression of SMC dedifferentiation • Reduction in atherosclerotic burden, • Promoted fibrous cap stability. |
|
| Axel D. (2001) [16] | mono- and transfilter co-cultures of human arteries SMC | 0.01 nM–10.0 mM ATRA | • Enhanced a-smooth muscle actin and heavy chain myosin expression | • Decrease in mRNA expression of the glycoproteins thrombospondin-1, fibronectin |
| Neuville P. (1999) [29] | Cultured aortic media and intimal thickening rat SMC, angioplasty of rat carotid artery and thoracic aorta | 10−6 final concentration, 0.5 mg/kg intraperitoneally/day for 14 days of RA | • Decreased α-smooth muscle actin in SMC cultured from the IT | • Reduced the intimal hyperplasia in the carotid artery in vivo |
| Wiegman P.J. (2000) [54] | Balloon angioplasty on rabbits with focal femoral atherosclerosis | 25 mg ATRA for the 3 days before and for 28 days after balloon injury | • More a-actin and desmin immunostaining | • Larger lumen area, internal elastic lamina, and external elastic lamina areas |
| Herdeg C. (2002) [55] | Right carotid artery of rabbits after induction of a fibromuscular plaque | 10 mL, 10 μM ATRA, local delivery with double-balloon catheter | • More intense a-actin staining pattern | • Reduced early neointimal proliferation and extent of stenosis |
| Colbert M. (1996) [56] | Transgenic mouse carrying lacZ transgene | • Inducing and maintaining smooth muscle differentiation in the developing ductus arteriosus • Promote the expression of the adult vascular phenotype |
• Appearance of smooth muscle myosin heavy chain isoform | |
| Haller H. (1995) [57] | VSMC of rat aortas | 10−9 mol/L ATRA for 12 and 48 h | • Inhibition of differentiation through increase in PKC-a expression and PKC activity | • Elevated expression of PKC and PKC-a in differentiated cultured SMC |
| Gollasch M. (1998) [58] | rat aortic (A7r5) VSMC cultures | 10−8 M ATRA for 48 h | • Increase in the number of functional Ca2+ channel | • L-type Ca2+ channel is a novel marker for differentiation of VSMC • Correlation of L-type Ca2+ α1-subunits expression with alpha-SMA and SM-MHC expression |
| Rogers M. (2024) [59] | human coronary artery SMC | 1 μmol/L ATRA, 1 μmol/L 9-cis RA | • Inhibition of SMC differentiation into osteoblast-like phenotype | |
| Wang C. (2008) [60] | VSMC of thoracic aorta of male rats | 5, 10 or 20 mM of ATRA | • Inhibition of proliferation and migration of VSMCs through upregulation of KLF4, differentiation marker genes (SM22a, alpha-SMA) and KLF4 target genes p53 | • Downregulation of SMemb |
| Meng F. (2009) [61] | VSMC of thoracic aorta of male rats | 10 μM ATRA | • Induction of HDAC2 phosphorylation mediated by JNK signaling leading to the increase in KLF4 acetylation | • Inhibition of the interaction between KLF4 and HDAC2 |
| Yu K. (2011) [62] | VSMC of thoracic aorta of male rats | 5, 10, or 20 mM ATRA | • Activation of SM22α expression • Stimulation of KLF4 acetylation by induction of KLF4 phosphorylation |
|
| Shi J. (2012) [63] | VSMC of thoracic aorta of male rats | 10 μM ATRA | • RARα mediated ATRA-KLF4 expression | |
| Wei S. (2018) [51] | VSMC of thoracic aorta of rats | 0, 5, 10, 20 μmol/L ATRA | • Suppression of dedifferentiation through RARα induced ZFP580 expression via the PI3K/Akt pathways |
alpha-SMA: alpha-smooth muscle actin, ATRA: all-trans retinoic acid, HDAC2: histone deacetylase 2, IT: intima thickening, KLF4: krüppel-like factor 4, PKC: protein kinase-C, SM22a: SMC: smooth muscle cell, SMemb: myosin heavy chain-B, SM-MHC: smooth muscle myosin heavy chain, PI3K: phosphatidylinositol 3-kinase, RARα: retinoic acid receptor α, VSMC: vascular smooth muscle cell.