Abstract:

Ventricular remodeling following myocardial infarction (MI) and its associated myocardial fibrosis represent a core pathological mechanism in the progression of heart failure. Accumulating evidence confirms that the spatiotemporal dynamics of immune cells play a crucial role in post-MI ventricular remodeling, spanning the entire process of cardiac inflammation, tissue repair, and fibrosis. MI not only triggers a local inflammatory response but also remotely regulates hematopoietic organs such as the bone marrow and spleen via pathways including inflammatory factor release and sympathetic nervous system activation. This drives hematopoietic stem/progenitor cells (HSPCs) to differentiate with a bias toward the myeloid lineage, resulting in a hematopoietic imbalance phenomenon described as "myeloid upsurge-lymphoid decline". This imbalance is characterized by excessive proliferation and release of proinflammatory myeloid cells, such as neutrophils and monocytes/macrophages, alongside a relative reduction in lymphoid cells like T cells and B cells. This systemic immune imbalance reshapes the immune cell composition in the heart and peripheral organs. It exacerbates sustained cardiac inflammation, oxidative stress, cell apoptosis, and excessive extracellular matrix deposition, ultimately leading to aggravated cardiac fibrosis, ventricular dilation, and systolic function deterioration. It is a key driver of adverse post-MI remodeling and the onset of heart failure. This article aims to systematically explore the spatiotemporal dynamics and functional characteristics of immune cell subsets driven by this post-MI hematopoietic imbalance. Furthermore, it proposes novel intervention strategies focused on precisely modulating hematopoietic stem cell differentiation pathway and key immune cell subsets. These strategies aim to improve the cardiac inflammatory microenvironment, delay the fibrotic process, and inhibit adverse ventricular remodeling, thereby offering potential therapeutic targets for preventing and treating post-MI heart failure.

Key words: myocardial infarction, hematopoietic imbalance, ventricular remodeling, immune lineage