HSPD1 regulates angiotensin II‑induced atrial fibrillation via the PPAR signaling pathway.

Abstract

Atrial fibrillation (AF) is a multifactorial condition, and understanding its molecular mechanisms is key for developing targeted therapies. The present study aimed to investigate the role of heat shock protein D1 (HSPD1) in the pathogenesis of AF, particularly in angiotensin II (Ang II)‑induced cardiac fibroblasts (CFs). Differentially expressed genes (DEGs) were screened from the GSE31821 dataset for enrichment analysis, protein‑protein interaction (PPI) network construction and the hub gene HSPD1 was identified. In vitro experiments, including Cell Counting Kit‑8 and Transwell migration assay, Reverse transcription‑quantitative (RT‑q)PCR, Western blotting and ELISA, were conducted to evaluated the effects of Ang II on CF viability, migration, fibrosis‑associated markers (collagen I, collagen III and α‑smooth muscle actin) and HSPD1 expression. The effects of HSPD1 knockdown on cell viability, inflammatory cytokines (TNF‑α, IL‑8 and IL‑1β), AF‑associated proteins [atrial natriuretic peptide (ANP), β‑major histocompatibility complex (MHC) and MMP‑2] and peroxisome proliferator‑activated receptor (PPAR) signaling pathways were investigated. A total of 582 DEGs were identified, with significant involvement of pathways such as 'MAPK signaling pathway' and 'Wnt signaling pathway'. A total of five genes (HSP90AA1, HSP90AB1, HSPA4, HSPA8 and HSPD1) were highly expressed in AF samples. In vitro, Ang II‑induced fibrotic changes in CFs included increased viability, migration and upregulated fibrosis markers and HSPD1 expression. HSPD1 knockdown decreased Ang II‑induced secretion of inflammatory cytokines (TNF‑α, IL‑8 and IL‑1β) and expression of AF‑associated proteins (ANP, β‑MHC and MMP‑2). Downregulation of PPAR signaling proteins (PPARα, PPARγ, carnitine palmitoyltransferase I and sirtuin3) were observed, while thiazolidinedione treatment partially prevented Ang II‑induced changes. HSPD1 serves a key role in Ang II‑induced CF function, promoting fibrosis, inflammation and AF‑associated protein expression. Targeting HSPD1 in combination with PPAR pathway modulation presents a promising therapeutic strategy for AF treatment.