ABSTRACT
The excessive inflammatory response induced by myocardial infarction exacerbates heart injury and leads to the development of heart failure. Recent studies have confirmed the involvement of multiple transcription factors in the modulation of cardiovascular disease processes. However, the role of KLF9 in the inflammatory response induced by cardiovascular diseases including myocardial infarction remains unclear. Here, we found that the expression of KLF9 significantly increased during myocardial infarction. Besides, we also detected high expression of KLF9 in infiltrated macrophages after myocardial infarction. Our functional studies revealed that KLF9 deficiency prevented cardiac function and adverse cardiac remodeling. Furthermore, the downregulation of KLF9 inhibited the activation of NF-κB and MAPK signaling, leading to the suppression of inflammatory responses of macrophages triggered by myocardial infarction. Mechanistically, KLF9 was directly bound to the TLR2 promoter to enhance its expression, subsequently promoting the activation of inflammation-related signaling pathways. Our results suggested that KLF9 is a pro-inflammatory transcription factor in macrophages and targeting KLF9 may be a novel therapeutic strategy for ischemic heart disease.
ABSTRACT
Highly efficient and charge-selective adsorption and desorption of peptides at trace level by a solid-phase adsorbent is described. The adsorbent of SiO2@PEI is synthesized by covalent immobilization of branched polyethylenimines (PEI) exclusively on the outer surface of the porous silica particles (â¼300 µm). For aqueous peptides (Mw = 600-3000 Da), SiO2@PEI can capture the negatively charged ones and leave the positively charged ones intact, and by adjusting pH of the system peptides with different isoelectric points (pIs) can be well separated. Targeted peptide at low abundance (at least as low as 0.1 mol % with respect to the highest one) can be well separated. The association constants of K > 10(12) M(-1) at pH > pI and K < 10(4) M(-1) at pH < pI are found; that is, selectivity > 10(8) is generally available. Thus, a peptide even at sub-femtomolar level can be extracted and eluted for analysis, and efficient recovery (79-92%) of the peptides is found. The extraction is mainly promoted by multisite electrostatic interaction, and the hydrophilic and cationic properties of PEI at low pH play a unique role in desorption efficiency and selectivity. The unbiased nature of this method renders the adsorbent applicable to the efficient separation of a broad spectrum of peptides, including those with similar pIs.
