From knowledge frontier to mechanistic core: bibliometric and systematic analysis of KLF9 in cardiovascular disease

Background: The Krüppel-like factor 9 (KLF9) is an emerging transcription factor that has garnered substantial attention in oncology, neuroscience, and metabolism research. However, the global research landscape and functional mechanisms of KLF9 in cardiovascular disease remain inadequately synthesized. This study aims to comprehensively delineate the research trajectory of KLF9 in cardiovascular science and systematically evaluate its specific roles and molecular mechanisms in cardiac pathophysiology through integrated bibliometric analysis and systematic review. Methods: Bibliometric analysis was conducted using the Web of Science Core Collection (WoSCC), searching publications from database inception to December 3, 2025, with visualization performed in VOSviewer and CiteSpace. For systematic review, PubMed, WoSCC, and Embase were searched from inception to November 20, 2025. Inclusion criteria encompassed original studies ( in vitro , in vivo , or human) investigating KLF9 function with mechanistic validation in the cardiovascular system. Exclusion criteria comprised non-English publications, non-original articles, and studies lacking mechanistic exploration. Risk of bias was assessed using the SYRCLE (Systematic Review Centre for Laboratory animal Experimentation) tool for animal studies and a customized 9-item checklist based on ToxRTool for cell experiments. Due to substantial between-study heterogeneity, narrative synthesis rather than meta-analysis was employed. Results: Bibliometric analysis identified cardiovascular research as the smallest and most nascent KLF9 subfield despite growing interest. Systematic synthesis included 11 studies (9 animal experiments, 8 cell experiments). It revealed KLF9 as a context-dependent regulator orchestrating post-infarction inflammation and repair, oxidative stress, mitochondrial homeostasis, metabolic adaptation, and pathological remodeling. Notably, KLF9 exerts dual, temporally regulated effects—exacerbating acute injury while remaining indispensable for proper infarct repair. Conclusions: By combining quantitative mapping with qualitative synthesis, this review suggests that KLF9 may serve as a functionally important yet understudied node in cardiac pathophysiology, highlighting the potential need for spatiotemporally precise, cell-type-specific targeting strategies in future research.