Atorvastatin Attenuates Human Cardiac Fibroblast Activation, with Associated Changes in GATA4/MEF2C and Selected Fibrosis-Related microRNAs.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Atorvastatin*/pharmacology ; MicroRNAs*/genetics ; MicroRNAs*/metabolism ; MEF2 Transcription Factors*/metabolism ; MEF2 Transcription Factors*/genetics ; Fibroblasts*/metabolism ; Fibroblasts*/drug effects ; GATA4 Transcription Factor*/metabolism ; GATA4 Transcription Factor*/genetics ; Myocardium*/metabolism ; Myocardium*/pathology ; Myocardium*/cytology; Gene Expression Regulation/drug effects ; Myofibroblasts/metabolism ; Myofibroblasts/drug effects ; Actins/metabolism ; Actins/genetics ; Humans ; Fibrosis ; Cells, Cultured

Cardiac fibroblast activation into α-smooth muscle actin (α-SMA)-expressing myofibroblasts is a central event in the progression of cardiac fibrosis. Therapeutic strategies capable of reversing or inhibiting this phenotypic transition are therefore of critical interest. Here, we explore associative changes in transcriptional and post-transcriptional regulators linked to fibroblast activation following atorvastatin exposure in primary human cardiac fibroblasts (HCFs). Atorvastatin treatment (10 µM) was associated with a reduction in α-SMA expression, consistent with decreased myofibroblast activation. This change co-occurred with reduced expression of the transcription factors GATA4 and MEF2C, which are implicated in cardiac cell identity and plasticity. Concurrently, atorvastatin treatment was associated with selective increase in specific fibrosis-related microRNAs, including miR-24, miR-26a, and miR-133a, whereas the expression of miR-21 and miR-23a remained unchanged. Together, these findings describe a coordinated pattern of transcriptional and post-transcriptional changes associated with atorvastatin exposure in HCFs, consistent with a shift away from the myofibroblast phenotype. These observations provide descriptive, hypothesis-generating insight into potential regulatory patterns associated with atorvastatin treatment, although further functional studies are required to establish causal relationships and translational relevance.

APVV-23-0557 Slovak Research and Development Agency; VEGA 1/0523/25 VEGA

Keywords: GATA4; MEF2C; atorvastatin; cardiac fibrosis; microRNAs; myofibroblasts

A0JWA85V8F (Atorvastatin)
0 (MicroRNAs)
0 (MEF2 Transcription Factors)
0 (GATA4 Transcription Factor)
0 (MEF2C protein, human)
0 (GATA4 protein, human)
0 (Actins)

Date Created: 20260513 Date Completed: 20260513 Latest Revision: 20260515

20260515

PMC13163429

10.3390/ijms27094146

42123723