Tanshinone â
¡A inhibits VSMC inflammation and proliferation in vivo and in vitro by downregulating miR-712-5p expression.
Eur J Pharmacol
; 880: 173140, 2020 Aug 05.
Article
in En
| MEDLINE
| ID: mdl-32387370
ABSTRACT
The inflammation and proliferation of vascular smooth muscle cells (VSMCs) are the basic pathological feature of proliferative vascular diseases. Tanshinone â
¡A (Tan â
¡A), which is the most abundant fat-soluble element extracted from Salvia miltiorrhiza, has potent protective effects on the cardiovascular system. However, the underlying mechanism is still not fully understood. Here, we show that Tan â
¡A significantly inhibits neointimal formation and decreases VSMC inflammation by upregulating the expression of KLF4 and inhibiting the activation of NFκB signaling. Using a microRNA array analysis, we found that miR-712-5p expression is significantly upregulated in tumor necrosis factor alpha (TNF-α)-treated VSMCs. Loss- and gain-of-function experiments revealed that transfection of miR-712-5p mimic promotes, whereas depletion of miR-712-5p suppresses TNF-α-induced VSMC inflammation, leading to amelioration of intimal hyperplasia induced by carotid artery ligation. Moreover, depletion of miR-712-5p by its antagomir largely abrogates TNF-α-induced VSMC proliferation. Our findings suggest that miR-712-5p mediates the stimulatory effect of TNF-α on VSMC inflammation, and that Tan â
¡A inhibits VSMC inflammation and proliferation in vivo and in vitro by suppression of miR-712-5p expression. Targeting miR-712-5p may be a novel therapeutic strategy to prevent proliferative vascular diseases.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myocytes, Smooth Muscle
/
MicroRNAs
/
Abietanes
/
Anti-Inflammatory Agents
Limits:
Animals
Language:
En
Journal:
Eur J Pharmacol
Year:
2020
Document type:
Article
Affiliation country:
China