The Influence of Metabolic Risk Factors on the Inflammatory Response Triggered by Myocardial Infarction: Bridging Pathophysiology to Treatment

Figure 1. Necrotic cardiomyocytes generate danger-associated molecular patterns (DAMPs) acting as danger signals on different immune cells through pattern recognition receptors (PRRs), enhancing cytokine release and local inflammatory response. High-mobility group box 1 protein (HMGB1); toll-like receptors (TLRs); receptors for advanced glycation end products (RAGEs); heat-shock proteins (HSPs); tumor necrosis factor-alpha (TNF-α); interleukin (IL); mitochondrial DNA (mtDNA); nuclear factor-kappa light chain enhancer of activated B cells (NFκB); receptor-associated kinase 1 (IRAK1); mitogen-activated protein kinase (MAPK); Nucleotide-binding Oligomerization Domain (NOD)-like receptors pyrin domain containing 3 (NLRP3). Illustration created with BioRender.

Figure 2. Bone marrow and splenic hematopoiesis fuel the cardiac inflammatory response during myocardial infarction (MI). In the bone marrow, granulocyte colony-stimulating factor (G-CSF) and granulocyte–macrophage colony-stimulating factor (GM-CSF), along with various inflammatory mediators, stimulate the proliferation and release of granulocytes and monocytes into the bloodstream. This process is further supported by sympathetic nervous system fibers since they decrease chemokine motif ligand 12 (CXCL12) activity, promoting Hematopoietic stem cells (HSC) release. In the spleen, angiotensin II (Ang II) enhances the motility and migration of resident monocyte populations, while interleukin-1β (IL-1β) triggers extramedullary hematopoiesis. This process involves the interaction of bone marrow-released HSCs with CD169+ macrophages via vascular cell adhesion molecule 1 (VCAM-1). Consequently, inflammatory cells migrate into the infarcted heart. Neutrophils infiltrate the cardiac tissue through β2-integrin and P-selectin, producing reactive oxygen species (ROS) and chemokines that facilitate the transmigration of dendritic cells and monocytes into the damaged tissue, creating a positive…

Figure 3. The role of macrophages, dendritic cells, and lymphocytes in the healing process post-myocardial infarction (MI). Monocytes are recruited to the infarcted heart, where they differentiate into activated macrophages, increasing immune cell recruitment and promoting the inflammatory response. Over time, macrophages remove necrotic cells and shift toward an anti-inflammatory phenotype, producing interleukin 10 (IL-10). Dendritic cells present antigenic proteins that shift the fibroblast phenotype toward a proinflammatory state, producing extracellular matrix proteins to maintain myocardial integrity. T and B lymphocyte activation triggers myocardial destruction and interferon gamma (IFN-γ) and IL-17 release. Activated B cells increase C-C motif ligand 7 and release IL-10, which enhance cardiac repair and wound healing. Reactive oxygen species (ROS); monocyte chemoattractant protein-1 (MCP-1); C-C motif chemokine receptor 2 (CCR2); vascular cell adhesion molecule 1 (VCAM-1); tumor necrosis factor-alpha (TNF-α); toll-like receptors (TLRs); receptors for advanced glycation end products (RAGEs). Illustration created with BioRender.